Primary objective of the parent study

“The primary objective is to evaluate the efficacy of N-Acetyl-L-Leucine based on blinded raters’ clinical impression of change in severity (CI-CS) in the treatment of A-T.” (opens the source at this quote in a new tab)

Secondary and exploratory objectives of the parent study

“To assess the clinical efficacy of N-Acetyl-L-Leucine on symptoms of ataxia, functioning, and quality of life for patients with A-T” (opens the source at this quote in a new tab)
“To characterize the pharmacokinetics (PK) of N-Acetyl-L-Leucine in patients with A-T” (opens the source at this quote in a new tab)

Symptomatic and long-term questions addressed by the parent study and the extension phase

“The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the symptomatic treatment of A-T.” (opens the source at this quote in a new tab)
“The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the neuroprotective, disease-modifying treatment of A-T.” (opens the source at this quote in a new tab)

“The two treatment sequences in the parent study and extension phase enable the investigation of both the symptomatic (6 week) and long-term (1 year) safety and efficacy of treatment with N-acetyl-l-leucine.” (opens the source at this quote in a new tab)

Purpose of the extension phase

“The Extension Phase will collect information on the long-term safety, tolerability, pharmacokinetics (PK), and efficacy of IB1001 as a treatment for A-T for the purpose of further assessing the risk/ benefit balance of the investigational medicinal product in the proposed clinical setting.” (opens the source at this quote in a new tab)

Registry dates and status

Field	Quoted record
Study start (actual)	“2020-01-08”
Primary completion (actual)	“2025-02-11”
Study completion (actual)	“2025-10-27”
Results first posted	“2026-03-25”
Recruitment status	“Terminated”

Registry study sites

Country	Site
United States	“University of California - Los Angeles”
Germany	“University of Giessen”
Spain	“Hospital Universitario La Paz”
United Kingdom	“Royal Papworth Hospital NHS Foundation Trust”

Planned number of centers

“The trial will be conducted in a total of approximately 6 centers in the United States, the United Kingdom, Germany, Spain, or an additional European site, which must meet the structural and personnel requirements for performing the planned regular trial-related investigations.” (opens the source at this quote in a new tab)

Period of participation and number of hospitals

“The study was conducted at 4 multinational research hospitals in Europe, the UK, and the US.” (opens the source at this quote in a new tab)
“In total, 17 patients with A-T participated in the study between 30-Jan-2020 and 11-Feb-2025.” (opens the source at this quote in a new tab)

Recruitment delay during the COVID-19 pandemic

“Initial recruitment for the study was substantially delayed by the COVID-19 pandemic, which significantly limited the ability to enroll subjects or for subjects to attend clinical study visits.” (opens the source at this quote in a new tab)

Termination before target recruitment

“The IB1001-203 clinical study was terminated prior to reaching the target recruitment.” (opens the source at this quote in a new tab)
“It was later determined by the Sponsor that a Phase III, double-blind, randomized, placebo-controlled study for A-T should be conducted to support the marketing application with IB1001 for A-T.” (opens the source at this quote in a new tab)
“Accordingly, an abbreviated clinical study report (CSR) is presented for this IB1001-203 study.” (opens the source at this quote in a new tab)

Multinational, open-label, rater-blinded phase 2 study

“This is a multinational, multicenter, open-label, rater-blinded prospective Phase II study which will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the treatment of Ataxia-Telangiectasia (A-T).” (opens the source at this quote in a new tab)

Design field	Quoted record
Phase	“Phase 2”
Allocation	“Non-Randomized”
Interventional model	“Single Group Assignment”
Masking	“Single (Outcomes Assessor)”

Baseline, treatment, and washout periods of the parent study

“Patients will be assessed during three study phases: a baseline period, a 6-week treatment period, and a 6-week post-treatment washout period.” (opens the source at this quote in a new tab)
“All patients will receive the study drug during this study.” (opens the source at this quote in a new tab)
“For each individual patient, the study lasts for approximately 3.5 - 4 months during which there are 6 study visits to the study site.” (opens the source at this quote in a new tab)

“Patients will be assessed twice during each period to allow an assessment of intra-patient variability.” (opens the source at this quote in a new tab)

Post-treatment washout as the within-participant control

“Second, each patient’s washout period (assessment B) serves as a control arm to their treatment period (assessment A).” (opens the source at this quote in a new tab)

Blinded rating of video recordings

“The primary evaluation of the Clinical Impression of Change in Severity (CI-CS; Primary Endpoint) will be performed by two independent neurologists whose assessments are based on videos of patient's performance on either the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or the 8 Meter Walk Test (8MWT) taken at each visit.” (opens the source at this quote in a new tab)

“The CI-CS assessment is ultimately performed by independent, blinded raters who compare videos of the primary anchor test from three periods: baseline, the end of treatment, and the end of a post-treatment washout.” (opens the source at this quote in a new tab)
“Pairs A, B, and C are reviewed by the raters in random order.” (opens the source at this quote in a new tab)
“The raters will be blinded in this way to reduce detection and performance biases.” (opens the source at this quote in a new tab)

Choice of an open-label design over a placebo-controlled crossover design

“A formal feasibility study was initiated by the Sponsor that demonstrated that a long-term, randomized, double-blind, placebo-controlled, crossover study would be difficult to recruit and carry out without changes to the study design.” (opens the source at this quote in a new tab)
“This was largely attributed to the known, widespread, off-label/unlicensed use of N-acetyl-dl-leucine (Tanganil®).” (opens the source at this quote in a new tab)
“In order to assure the feasibility of recruitment, an open-label study schema is used.” (opens the source at this quote in a new tab)

“IntraBio initially proposed to investigate the safety and efficacy of N-Acetyl-L-Leucine for NPC, Tay-Sachs disease, and inherited Cerebellar Ataxias in a randomized, double-blind, placebo-controlled, crossover study.” (opens the source at this quote in a new tab)
“During the trial, naïve patients will be without study drug for 6 out of 12 weeks (compared previously to 18 out of 24 weeks) and non-naïve patients will be without study drug for 14 of 20 weeks (compared previously to 24 out of 30 weeks).” (opens the source at this quote in a new tab)

Screening for prior use of the racemate

“Given the known unlicensed use of the racemate (Tanganil®), for all patients, a urine sample will be taken at visit 1 to detect N-acetyl-d-leucine using a validated liquid chromatography mass spectrometry/mass spectrometry method.” (opens the source at this quote in a new tab)
“Patients who fail two urine N-acetyl-d-leucine tests (e.g., visit 1 and repeat visit 1) are ineligible for the study.” (opens the source at this quote in a new tab)

Extension phase: two 1-year treatment periods separated by a washout

“This Extension Phase allows patients who have completed the Parent Study to, at the discretion of the Principal Investigator (PI), continue treatment with N-Acetyl-L-Leucine (IB1001).” (opens the source at this quote in a new tab)
“Patients will receive treatment with IB1001 for two one-year treatment periods, separated by a 6-week washout.” (opens the source at this quote in a new tab)
“For each individual patient, the Extension Phase lasts for approximately 25.5 months, during which there are 6 visits to the study site.” (opens the source at this quote in a new tab)

“Protocol Amendment 6.0 introduces an additional year of dosing upon completion of the extension-phase washout Visit 10.” (opens the source at this quote in a new tab)
“This study is not blinded.” (opens the source at this quote in a new tab)

One of three trials under a master protocol

“The IB1001-201 (NPC), IB1001-202 (GM2), and IB1001-203 (A-T) clinical trials are separate multinational, multicenter, open-label, rater-blinded phase II studies.” (opens the source at this quote in a new tab)
“Data from the three clinical trials will be analyzed separately.” (opens the source at this quote in a new tab)

Independent data safety monitoring board

“The safety, integrity, and feasibility of the trial is monitored by an independent data safety monitoring board (DSMB) consisting of three independent, non-participating members (including two clinicians and a statistician).” (opens the source at this quote in a new tab)

Key inclusion criteria

Criterion	Quoted record
Age and diagnosis	“Male or female aged ≥6 years with a confirmed diagnosis of A-T at the time of signing informed consent.”
Ataxia severity	“A Scale for the assessment and rating of ataxia (SARA) score of 5 ≤ X ≤ 33 points (out of 40)”
Gait	“Within the 2-7 range (out of 0-8 range) of the Gait subtest of the SARA scale”
Fine motor function	“Be able to perform the 9 Hole Peg Test with Dominant Hand (9HPT-D) (SCAFI subtest) in 20 ≤ X ≤150 seconds.”
Body weight	“Weight ≥15 kg at screening.”

Age limit by region in the master protocol

“IB1001-203 (A-T): Male or female aged ≥6 years in Europe OR ≥18 years in the United States with a confirmed genetic diagnosis of A-T at the time of signing informed consent.” (opens the source at this quote in a new tab)

Key exclusion criteria

Criterion	Quoted record
Symptom status	“Asymptomatic patients”
Genetic testing	“Patient has clinical features of A-T, but a completely negative result on a previous genetic test for A-T.”
Gastrointestinal	“Chronic diarrhea;”
Vision	“Unexplained visual loss;”
Cancer	“Malignancies;”
Diabetes	“Insulin-dependent diabetes mellitus.”
Hypersensitivity	“Known history of hypersensitivity to the N-Acetyl-Leucine (DL-, L-, D-) or derivatives.”
Other studies	“Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product (IMP; 'study drug') within 6 weeks prior to Visit 1.”
Pregnancy	“Current or planned pregnancy or women who are breastfeeding.”

Prohibited medications and washout

“Patients unwilling and/or not able to undergo a 6-week washout period from any of the following prohibited medication prior to Visit 1 (Baseline 1) and remain without prohibited medication through Visit 6.” (opens the source at this quote in a new tab)

Prohibited medication	Quoted record
Aminopyridines	“Aminopyridines (including sustained-release form);”
Racemate	“N-Acetyl-DL-Leucine (e.g. Tanganil®);”
L-enantiomer from another source	“N-Acetyl-L-Leucine (prohibited if not provided as IMP);”
Riluzole	“Riluzole;”
Gabapentin	“Gabapentin;”
Varenicline	“Varenicline;”
Chlorzoxazone	“Chlorzoxazone;”
Sulfasalazine	“Sulfasalazine;”
Rosuvastatin	“Rosuvastatin.”

Entry to the extension phase

“This Extension Phase will enroll patients who have completed Visit 6 of the parent study phase of IB1001-203.” (opens the source at this quote in a new tab)
“Recruitment into the Extension Phase will continue until all patients who participated in the parent study, and who are willing and eligible to participate in the Extension Phase, are enrolled.” (opens the source at this quote in a new tab)

Dose by age and body weight

Age and weight group	Registry description of treatment
13 years or older	“Patients ≥13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day).”
6 to 12 years, 15 to less than 25 kg	“Patients aged 6-12 years weighing 15 to <25 kg will take 2 g per day: 1 g in the morning and 1 g in the evening.”
6 to 12 years, 25 to less than 35 kg	“Patients aged 6-12 years weighing 25 to <35 kg will take 3 g per day: 1 g in the morning, 1 g in the afternoon, and 1 g in the evening.”
6 to 12 years, 35 kg or more	“Patients aged 6-12 years weighing ≥35 kg will take 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults)”

Treatment and washout duration in the parent study

“6-weeks treatment with IB1001 administered orally.” (opens the source at this quote in a new tab)
“After the 6-week treatment period, patients will enter a 6-week post-treatment washout period.” (opens the source at this quote in a new tab)

Formulation in the parent study and the extension phase

“In the parent study, the dosage formulation of N-acetyl-l-leucine is 1000 mg powder for oral suspension (manufacture: Patheon UK Limited, Oxfordshire, UK) which is suspended in 40 mL Ora-Blend®.” (opens the source at this quote in a new tab)
“In the extension phase, the dosage form of N-acetyl-l-leucine is 1000 mg granules for oral suspension in a sachet (manufacture: Patheon UK Limited, Oxfordshire, UK, and Patheon France S.A.S., Bourgoin, France) which is suspended in 40 mL water.” (opens the source at this quote in a new tab)

Timing with meals, dose reduction, and compliance

“Medication should be taken at least 30 min before or at least 2 h after a meal.” (opens the source at this quote in a new tab)
“If adverse events are noted, patients are permitted to down-titrate to one-half their daily dose, at the direction of the investigator.” (opens the source at this quote in a new tab)
“Compliance will be assessed upon a review of the inventory of IB1001 bottles/sachets returned by patients.” (opens the source at this quote in a new tab)

Extension phase treatment periods

“From Visit 7B onward, all patients will receive treatment with N-Acetyl-L-Leucine for 365 days (+/-14 days).” (opens the source at this quote in a new tab)
“After Visit 9, all patients will enter a 42-day (+14 days) washout phase.” (opens the source at this quote in a new tab)
“From Visit 10 onward, all patients will receive treatment with N-Acetyl-L-Leucine for 365 days (+/-14 days).” (opens the source at this quote in a new tab)

Permitted concomitant therapies

“Non-prohibited medications/therapies (e.g. concomitant speech therapy, and physiotherapy) are permitted provided:” (opens the source at this quote in a new tab)
“Patients have been on a stable dose/duration and type of therapy for at least 6 weeks before Visit 1 (Baseline 1)” (opens the source at this quote in a new tab)
“Patients are willing to maintain a stable dose/do not change their therapy throughout the duration of the study.” (opens the source at this quote in a new tab)

Definition of the primary endpoint

“The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse).” (opens the source at this quote in a new tab)
“Change values were calculated for each period, i.e. treatment with IB1001 (comparing the end of treatment (Visit 4) with baseline (Visit 2)) and post-treatment washout (comparing the end of washout (Visit 6) with the end of treatment (Visit 4)).” (opens the source at this quote in a new tab)
“Then, the mean change obtained in the post-treatment period was subtracted from the mean change obtained for the treatment with IB1001 period, with a positive value indicating an improvement in the treatment period compared to the post-treatment washout period.” (opens the source at this quote in a new tab)

Sponsor rationale: heterogeneous presentation and an individually chosen anchor test

“Given the heterogeneity of symptoms, the appointment of a single symptom scale, such as either the 8-m walk test (8MWT) or the 9-hole peg test of the dominant hand (9HPT-D), as the primary outcome measure is not appropriate for patient populations.” (opens the source at this quote in a new tab)
“The primary anchor test remains fixed for each patient for the duration of the study.” (opens the source at this quote in a new tab)
“Finally, the CI-CS is a platform to capture and assess small but clinically meaningful changes in patient’s performance, which relate to their level of functioning and quality of life, but which cannot be obtained from the quantitative timed 8MWT or 9HPT-D assessments.” (opens the source at this quote in a new tab)

Sponsor rationale: use of the CI-CS in place of the SARA

“At the recommendation of the US FDA, the novel CI-CS endpoint is used in lieu of the traditional SARA scale as the primary outcome measure because it has been developed to assess and reflect a clinically meaningful change in function” (opens the source at this quote in a new tab)
“In addition to adding blinded control to the primary assessment, at the recommendation of the US FDA, videos will be used to increase reliability and minimize testing burden on patients.” (opens the source at this quote in a new tab)

Scoring by two raters and adjudication

“If there is a difference of one (1) point in the two primary blinded raters’ CI-CS scores for a specific video pairing, the two scores will be averaged.” (opens the source at this quote in a new tab)
“If there is a difference greater than one (1) point between the two primary blinded reviewers’ CI-CS scores for a specific video pairing, an adjudication rating will be triggered.” (opens the source at this quote in a new tab)

Key secondary endpoint: Clinical Impression of Severity

“The Change in Severity assessment will instruct the blinded rater to consider the severity of the patient at each visit.” (opens the source at this quote in a new tab)
“Then, the mean change in the post-treatment period was subtracted from the mean change in the treatment with IB1001 period.” (opens the source at this quote in a new tab)

Other secondary endpoints

Endpoint	Registry description
SARA	“The Scale for Assessment and Rating of Ataxia has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test. The range is 0-40 points, with a lower score representing neurological improvement and a higher score representing neurological worsening.”
SCAFI	“The SCAFI total score was calculated as the arithmetic mean of the non-missing Z-scores for the 3. A higher total score means better performance.”
EQ-5D	“EQ-5D VAS is a 0-100 scale where patients are asked to indicate their overall health, with a score of 0 indicating worst health and a score of 100 indicating best health.”
Clinical Global Impression of Change	“The Clinical Global Impression of Change assessed by the investigator is evaluated on a 7 point Likert scale ranging from 1='very much improved' to 7='very much worse'”

Extension phase primary endpoint in the 2021 master protocol

“In the extension phase, the primary endpoint is defined as success on the Clinical Impression of Change in Severity© (CI-CS) comparing videos of the primary anchor test at (i) the end of the extension phase treatment with N-acetyl-l-leucine (visit 9) versus (ii) the extension phase baseline (visit 7).” (opens the source at this quote in a new tab)

Extension phase primary endpoint in protocol version 7.0

“The primary endpoint in this Extension Phase is success measured on the Scale for the Assessment and Rating of Ataxia (SARA) from the Extension Phase baseline (Visit 7) to the end of treatment in the Extension Phase (Visit 9).” (opens the source at this quote in a new tab)
“All endpoints in the extension phase are considered secondary to those in the Parent Study.” (opens the source at this quote in a new tab)

Extension phase endpoints as presented

“Methods: The primary endpoint was defined as the change from the Extension Phase baseline versus the end of the first year of treatment with NALL in the Extension Phase Treatment Period I on the Scale for the Assessment and Rating of Ataxia (SARA).” (opens the source at this quote in a new tab)

Planned enrollment

Population	Planned number
Enrolled	“To be enrolled: Approximately 39 patients”
Per protocol analysis	“To be analyzed according to the Per Protocol Analysis: Approximately 30 patients”

“Recruitment will continue until approximately 30 patients complete dosing and Visit 6 or approximately 39 patients are enrolled.” (opens the source at this quote in a new tab)

Sample size assumptions and power

“It is postulated that N-Acetyl-L-Leucine will show effectiveness in 30% of patients and this success rate is viewed as being clinically important.” (opens the source at this quote in a new tab)
“With 30 patients reporting on the primary endpoint, the study will have 76% power to detect a treatment benefit in a 5% one-sided one-sample t-test.” (opens the source at this quote in a new tab)

Participants enrolled and analyzed

Population	Participants
Enrolled (actual)	“17”
Analyzed for the primary endpoint	“16”

Extension phase sample size

“Sample size is determined by the number of patients that move into this Extension Phase from the parent study.” (opens the source at this quote in a new tab)

“Results: 12 patients aged 6 to 36 years have completed Visit 9 of the Extension Phase.” (opens the source at this quote in a new tab)

Modified intention-to-treat analysis set

“Modified Intention to Treat (mITT) Analysis Set is defined as all patients who receive at least one dose of the study drug and with one video recording during the baseline period (Visit 1 or 2, or both) and treatment period (Visit 3 or Visit 4, or both).” (opens the source at this quote in a new tab)

Safety and per protocol sets

“The Safety Analysis Set (SAF) will consist of all patients who receive at least one dose of study drug (N-Acetyl-L-Leucine)” (opens the source at this quote in a new tab)
“The primary analyses of efficacy will be based on the mITT.” (opens the source at this quote in a new tab)
“The SAF will be the basis for all analyses of safety and tolerability.” (opens the source at this quote in a new tab)

“Analyses will also be conducted on the per protocol analysis set which will consist of all patients with video recordings at baseline (visit 1 and/or visit 2), end of treatment (visit 3 and/or visit 4), and end of washout (visit 5 and/or visit 6) and without any major protocol deviations that can influence the validity of the data for the primary efficacy variable.” (opens the source at this quote in a new tab)

Planned primary analysis and multiplicity

“The analysis of the primary endpoint will be based on a single sample one-sided t test comparing the mean of the CI-CS differences with zero.” (opens the source at this quote in a new tab)
“The null hypothesis is that the mean is ≤ 0, with the alternative hypothesis that this mean is > 0, and the test will be conducted at the one-sided 5% significance level.” (opens the source at this quote in a new tab)
“All other endpoints will be evaluated descriptively.” (opens the source at this quote in a new tab)
“There will be no formal control of multiplicity across these endpoints.” (opens the source at this quote in a new tab)

Handling of missing video recordings

“If the visit 2 video is missing, the visit 1 video will be used in its place.” (opens the source at this quote in a new tab)
“Analyses based on the mITT analysis set will utilize a last observation carried forward approach for missing videos 5 and 6.” (opens the source at this quote in a new tab)
“For the primary endpoint CI-CS, this implies that the CI-CS value for visit 4 to visit 6 will be assigned the value 0 if both videos 5 and 6 are not available.” (opens the source at this quote in a new tab)

Extension phase analysis set and planned test

“The modified intention-to-treat analysis set Extension Phase (mITTe) will consist of all patients in the SAF with a SARA score at Visit 7 of the Extension Phase and either at Visit 8 or Visit 9 (or both)” (opens the source at this quote in a new tab)
“It is postulated that under standard of care, 90% of patients would worsen (higher score) in terms of their performance on the SARA scale over a 12-month period, while conversely only 10% would show similar performance or some improvement.” (opens the source at this quote in a new tab)
“All exploratory endpoints relating to the washout phase, or Extension Phase treatment period II, will be evaluated based on descriptive statistics.” (opens the source at this quote in a new tab)

Participant flow by study period

Study period	Started	Completed	Not completed
Treatment with IB1001	“17”	“16”	“1”
Post-treatment washout	“16”	“16”	“0”
Extension phase	“13”	“10”	“3”

Reasons for not completing

Study period	Reason	Participants
Treatment with IB1001	“Adverse Event”	“1”
Extension phase	“Adverse Event”	“1”
Extension phase	“Withdrawal by Subject”	“1”
Extension phase	“Lost to Follow-up”	“1”

Prior use of prohibited medications and consent to the extension phase

“All patients were naïve (i.e. they had not used any prohibited medications 42 days prior to the first dose of study drug in the Parent Study).” (opens the source at this quote in a new tab)
“The Extension Phase was not consented by 3 of the 16 patients who completed the Parent Period.” (opens the source at this quote in a new tab)

Participants with extension phase assessments

“Results: 12 patients aged 6 to 36 years have completed Visit 9 of the Extension Phase.” (opens the source at this quote in a new tab)
“Following the EP Washout Period, 7 patients completed treatment with NALL for an additional 1 year.” (opens the source at this quote in a new tab)

Age, sex, and ethnicity

Characteristic	Value
Participants	“17”
Age, mean (standard deviation), years	“23.3 (12.9)”
Female	“7”
Male	“10”
Hispanic or Latino	“2”
Not Hispanic or Latino	“15”

Clinical Global Impression of Severity at the baseline visits

Rater	Visit	Mean	Standard deviation
Treating physician	Visit 1	“4.2”	“1.1”
Treating physician	Visit 2	“4.2”	“1.1”
Caregiver	Visit 1	“3.5”	“2.0”
Caregiver	Visit 2	“3.1”	“2.0”
Participant	Visit 1	“2.8”	“1.8”
Participant	Visit 2	“2.3”	“1.6”

“This was rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill the patient has been/I have ever been.” (opens the source at this quote in a new tab)

Primary endpoint: CI-CS during treatment minus CI-CS during washout

Measure	Value
Participants analyzed	“16”
Mean (standard deviation), score on a scale	“0.16 (1.65)”

Components of the primary endpoint

Period	CI-CS, mean (standard deviation)
Treatment with IB1001 (Visit 4 versus Visit 2)	“0.16 (0.81)”
Post-treatment washout (Visit 6 versus Visit 4)	“0.00 (1.18)”

CI-CS reclassified on a 3-point scale, number of participants

Period	Worsened (-1)	No observable change (0)	Improved (+1)
Treatment with IB1001	“6”	“2”	“8”
Post-treatment washout	“7”	“1”	“8”

Key secondary endpoint: change in Clinical Impression of Severity

Measure	Value
Participants analyzed	“16”
Mean (standard deviation), score on a scale	“-0.09 (0.39)”

CI-CS for the non-primary anchor test

Period	CI-CS, mean (standard deviation)
Treatment with IB1001	“0.00 (1.07)”
Post-treatment washout	“0.17 (1.03)”

Change in SARA total score

Period	Change, mean (standard deviation)
Treatment with IB1001	“-0.31 (3.47)”
Post-treatment washout	“0.59 (2.99)”

Change in SCAFI total score

Period	Change, mean (standard deviation)
Treatment with IB1001	“0.0583 (0.3384)”
Post-treatment washout	“0.0157 (0.1923)”

Treating physician Clinical Global Impression of Change

Period	Mean	Standard deviation
Treatment with IB1001	“3.3”	“0.9”
Post-treatment washout	“4.8”	“0.9”

Treating physician Clinical Global Impression of Severity by visit

Visit	Mean	Standard deviation
Visit 2 (baseline)	“4.2”	“1.1”
Visit 3	“4.0”	“1.1”
Visit 4 (end of treatment)	“4.0”	“1.1”
Visit 5	“4.1”	“1.0”
Visit 6 (end of washout)	“4.1”	“0.9”

Sponsor summary of the parent study results

“The mean change during the treatment period indicated an improvement in the patients' condition at the end of the treatment period, while the mean CI-CS during the washout period (Visit 6 versus Visit 4) showed no change.” (opens the source at this quote in a new tab)

Extension phase: change in SARA after 1 year of treatment

“After 12 months of treatment, the mean change from baseline on the SARA -2.25 ± 3.16 points after receiving NALL (95% confidence interval [CI] -4.25 to-0.25; p=0.031).” (opens the source at this quote in a new tab)

Extension phase: change in SARA during the washout and after a second year

“The mean change in SARA for participants (n =11) during the Extension Phase Washout Period was 1.36 (SD=2.04) (95% confidence interval [CI] 0 to 2.73; p=0.25).” (opens the source at this quote in a new tab)
“The mean change in SARA score compared to the start of the Extension Phase was -0.33.” (opens the source at this quote in a new tab)

Extension phase: comparison with a natural history cohort

“Conclusion: In the IB1001-203 Extension Phase involving patients with A-T, treatment with NALL corresponded to a 340% reduction in annual disease progression after 1 year and 120% after 2 years compared to a natural history control cohort.” (opens the source at this quote in a new tab)

“In the extension phase, IB1001 met its primary SARA endpoint, showing a statistically significant, clinically meaningful slowing of disease progression and a neuroprotective effect.” (opens the source at this quote in a new tab)

Change in EQ-5D visual analogue scale

Period	Change, mean (standard deviation)
Treatment with IB1001	“4.9 (9.7)”
Post-treatment washout	“-0.8 (10.5)”

“For posting, health-related quality of life based on the EQ-5D visual analogue scale (VAS) was presented as a secondary endpoint.” (opens the source at this quote in a new tab)

Caregiver and participant Clinical Global Impression of Change

Rater	Period	Mean	Standard deviation
Caregiver	Treatment with IB1001	“3.1”	“0.8”
Caregiver	Post-treatment washout	“4.7”	“1.0”
Participant	Treatment with IB1001	“3.5”	“0.9”
Participant	Post-treatment washout	“4.7”	“1.1”

Caregiver and participant Clinical Global Impression of Severity by visit

Rater	Visit	Mean	Standard deviation
Caregiver	Visit 2 (baseline)	“3.1”	“2.0”
Caregiver	Visit 4 (end of treatment)	“2.9”	“1.5”
Caregiver	Visit 6 (end of washout)	“3.4”	“1.8”
Participant	Visit 2 (baseline)	“2.3”	“1.6”
Participant	Visit 4 (end of treatment)	“2.4”	“1.8”
Participant	Visit 6 (end of washout)	“2.9”	“1.8”

Deaths, serious adverse events, and other adverse events by period

Category	Treatment with IB1001	Post-treatment washout	Extension phase
All-cause mortality	“0/17 (0.00%)”	“0/17 (0.00%)”	“1/13 (7.69%)”
Serious adverse events	“1/17 (5.88%)”	“0/17 (0.00%)”	“2/13 (15.38%)”
Other (not including serious) adverse events	“9/17 (52.94%)”	“2/17 (11.76%)”	“11/13 (84.62%)”

Serious adverse events by term

Event	Treatment with IB1001	Post-treatment washout	Extension phase	Severity and relatedness
Gastrointestinal lymphoma	“1/17 (5.88%)”	“0/17 (0.00%)”	“0/13 (0.00%)”	“severe, not related”
Peritoneal mesothelioma malignant	“0/17 (0.00%)”	“0/17 (0.00%)”	“1/13 (7.69%)”	“severe, not related”
Intraductal proliferative breast lesion	“0/17 (0.00%)”	“0/17 (0.00%)”	“1/13 (7.69%)”	“moderate, not related”
Infection	“0/17 (0.00%)”	“0/17 (0.00%)”	“1/13 (7.69%)”	“severe, not related”
Mastitis	“0/17 (0.00%)”	“0/17 (0.00%)”	“1/13 (7.69%)”	“severe, not related”
Seroma	“0/17 (0.00%)”	“0/17 (0.00%)”	“1/13 (7.69%)”	“severe, not related”
Erythema	“0/17 (0.00%)”	“0/17 (0.00%)”	“1/13 (7.69%)”	“severe, not related”

Non-serious adverse events reported during the parent study

Event	Treatment with IB1001	Post-treatment washout
Abdominal pain upper	“2/17 (11.76%)”	“1/17 (5.88%)”
Nasopharyngitis	“1/17 (5.88%)”	“0/17 (0.00%)”
Oral herpes	“1/17 (5.88%)”	“0/17 (0.00%)”
Respiratory tract infection	“1/17 (5.88%)”	“0/17 (0.00%)”
Upper respiratory tract infection	“1/17 (5.88%)”	“0/17 (0.00%)”
Chorea	“1/17 (5.88%)”	“0/17 (0.00%)”
Syncope	“1/17 (5.88%)”	“0/17 (0.00%)”
Fatigue	“1/17 (5.88%)”	“0/17 (0.00%)”
Hypertransaminasaemia	“1/17 (5.88%)”	“0/17 (0.00%)”
Pollakiuria	“1/17 (5.88%)”	“0/17 (0.00%)”
Menstruation irregular	“1/17 (5.88%)”	“0/17 (0.00%)”
Cough	“1/17 (5.88%)”	“0/17 (0.00%)”
Hyperhydrosis	“1/17 (5.88%)”	“0/17 (0.00%)”
Gastrointestinal lymphoma	“1/17 (5.88%)”	“0/17 (0.00%)”
Diarrhoea	“0/17 (0.00%)”	“1/17 (5.88%)”
Muscle spasms	“0/17 (0.00%)”	“1/17 (5.88%)”

Non-serious adverse events reported during the extension phase

Event	Extension phase
Diarrhoea	“3/13 (23.08%)”
Nasopharyngitis	“2/13 (15.38%)”
Respiratory tract infection	“1/13 (7.69%)”
Bronchitis	“1/13 (7.69%)”
Candida infection	“1/13 (7.69%)”
Corona virus infection	“1/13 (7.69%)”
Dysphagia	“1/13 (7.69%)”
Vomiting	“1/13 (7.69%)”
Gait disturbance	“1/13 (7.69%)”
Fall	“1/13 (7.69%)”
Hand fracture	“1/13 (7.69%)”
B-lymphocyte count abnormal	“1/13 (7.69%)”
T-lymphocyte count abnormal	“1/13 (7.69%)”
Type 2 diabetes mellitus	“1/13 (7.69%)”
Muscle spasms	“1/13 (7.69%)”
Myalgia	“1/13 (7.69%)”
Speech disorder	“1/13 (7.69%)”
Tremor	“1/13 (7.69%)”
Micturition urgency	“1/13 (7.69%)”

Adverse events the sponsor considered related to the study drug

“During the parent study, 2 study drug-related adverse events were reported by 2 patients: abdominal pain (reported by 1 patient) and muscle spasms (reported by 1 patient).” (opens the source at this quote in a new tab)
“None of the study drug-related TEAEs was reported by more than one patient.” (opens the source at this quote in a new tab)
“The events were mild and transient.” (opens the source at this quote in a new tab)
“In the Extension Phase, 5 study drug-related adverse events were reported by 4 patients: diarrhoea (reported by 2 patients), and muscle spasms (reported by 1 patient)” (opens the source at this quote in a new tab)

Adverse event collection period

“For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767).” (opens the source at this quote in a new tab)

Summary

IB1001-203 was a single-group, open-label trial in which each participant's 6-week post-treatment washout served as the comparison for the 6-week treatment period. Blinded raters scored the primary endpoint from video recordings; the SARA, the SCAFI, and the clinical global impression scales were recorded at the study sites under open-label conditions. The protocol planned approximately 39 enrolled participants and calculated 76% power with 30 participants. The sponsor terminated the trial after 17 participants were enrolled, and 16 were analyzed. The registry posts a mean and standard deviation for each endpoint and no statistical test. The posted primary endpoint was a mean of 0.16 (standard deviation 1.65), and on the 3-point reclassification 8 of 16 participants were rated improved after treatment and 8 of 16 after washout. The extension phase was unblinded. Its primary endpoint was the CI-CS in the 2021 master protocol and the SARA in protocol version 7.0. Extension phase efficacy results are available from a conference abstract covering 12 participants at 1 year and 7 participants at 2 years, and the abstract does not describe the natural history cohort used for its comparison of progression rates.

Limitations and caveats posted by the sponsor

“This study was ongoing during the COVID-19 pandemic, and the conduct of this study was impacted by the COVID-19 pandemic.” (opens the source at this quote in a new tab)
“Accordingly, the IB1001-203 clinical study was terminated prior to reaching the target recruitment, to prioritize the pivotal Phase III trial.” (opens the source at this quote in a new tab)

Absence of a placebo group

“In the absence of a placebo, to minimize detection bias in the primary endpoint, the CI-CS assessment was performed by blinded, independent raters.” (opens the source at this quote in a new tab)

No correction for multiple comparisons

“A one-sided significance level of 5% will be used throughout for all endpoints as a guide for evidence for activity.” (opens the source at this quote in a new tab)
“No correction for multiple comparisons will be included.” (opens the source at this quote in a new tab)