HOPE-3

28 evidence topics · 10 sources

Objective

Efficacy and safety objective

“evaluating the efficacy and safety of a cell therapy called deramiocel” (opens the source at this quote in a new tab)

Location and study date

United States trial sites

“20 trial sites in USA” (opens the source at this quote in a new tab)

Enrollment period

Milestone	Reported date
Enrollment began	“June 22, 2022”
Enrollment ended	“May 28, 2024”

Study design

Randomization, masking, and comparator

“Randomized (1:1), double-blind, placebo-controlled study” (opens the source at this quote in a new tab)

Eligibility criteria

Age, ambulation, and cardiac eligibility

“Ages ≥ 10 who are late or non-ambulatory” (opens the source at this quote in a new tab)
“LVEF ≥ 35%” (opens the source at this quote in a new tab)

Upper-limb impairment criterion

“total PUL score less than or equal to 40” (opens the source at this quote in a new tab)

Treatment

Investigational dose, route, and treatment duration

“Participants received intravenous Deramiocel at 150 million cells per infusion or placebo every three months for a 12-month period.” (opens the source at this quote in a new tab)

Background corticosteroid therapy

“All patients on background stable corticosteroid therapy” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using performance of the upper limb 2.0 total score as the primary endpoint

Primary upper-limb instrument

“Performance of Upper Limb (PUL v2.0)” (opens the source at this quote in a new tab)

Outcome-instrument validation: PUL versions 1.2 and 2.0

“Our results confirm that the PUL 1.2 and 2.0 versions detect change in all domains over 2 years.” (opens the source at this quote in a new tab)

Outcome-instrument validation: patient perspectives on meaningful change in NSAA and PUL

“items that are meaningful differ based on ability level” (opens the source at this quote in a new tab)
“maintaining function in lower and upper limbs is the ultimate goal” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Sample-size assumptions in the publication

Assumption	Reported value
Planned participants per treatment group	“49”
Statistical power	“90%”

Randomized participants

Population	Participants
Total randomized	“106”
Allocated to deramiocel	“54”
Allocated to placebo	“52”

Description of analysis sets

Published analysis population

“intention-to-treat (ITT) population” (opens the source at this quote in a new tab)

Sponsor-described primary analysis

“prespecified repeated measures model using percent change from BL” (opens the source at this quote in a new tab)

Primary analysis populations compared by FDA

Analysis	Participants
Prespecified SAP 1.1	“104”
Post-study modified SAP 3.0	“105”

FDA assessment of statistical changes

“BLA submission included additional statistical changes without an associated, updated SAP.” (opens the source at this quote in a new tab)

Results

Participant disposition

Treatment non-initiation and discontinuations

Disposition	Participants
Deramiocel: did not receive treatment	“1”
Deramiocel: withdrew consent	“3”
Placebo: withdrew consent	“1”
Placebo: discontinuation due to an adverse event	“1”

Baseline characteristics

HOPE-3: baseline demographics

“Baseline Demographics”	“Overall (n=106)”
“Age (years)”/ “Mean (SD)”	“15.0 (3.04)”
“Min, Max”	“10, 22”
“Non-ambulatory”	“90 (84.9)”
“Diagnosed cardiomyopathy”/ “Yes”	“79 (74.5)”

Efficacy results

Published total PUL2.0 result: between-group difference in mean percentage change at month 12

“4·55% (95% CI 0·47–8·63; p=0·029)” (opens the source at this quote in a new tab)

HOPE-3: cardiac endpoint in the published trial

“The key secondary endpoint of left ventricular ejection fraction (LVEF) did not reach statistical significance, although the difference favoured deramiocel.” (opens the source at this quote in a new tab)
“p=0·0935” (opens the source at this quote in a new tab)

HOPE-3: FDA assessment of prespecified analyses

“The study did not meet its pre-specified primary and secondary efficacy endpoints” (opens the source at this quote in a new tab)

FDA analysis using the prespecified statistical analysis plan

Endpoint	Deramiocel minus placebo	Nominal p value
PUL 2.0 total score: absolute change	“0.66”	“0.24”
LVEF: change in percentage points	“-0.04%”	“0.97”

Health-related quality of life and patient-reported outcomes

Patient Global Impression of Severity: FDA mean difference and 95% confidence interval

“-0.25 (-0.60, 0.09)” (opens the source at this quote in a new tab)

Safety results

HOPE-3: safety table notation

“n (%), e” (opens the source at this quote in a new tab)

HOPE-3: headache and hypersensitivity reactions

“Event”	“Deramiocel (N=53)”	“Placebo (N=52)”
“Headache”	“32 (60.4), 91”	“2 (3.8), 2”
“Hypersensitivity Reactions”	“22 (41.5), 55”	“8 (15.4), 18”

Mortality during the controlled study

“No deaths occurred in the study.” (opens the source at this quote in a new tab)

Study limitations

Summary

HOPE-3 randomized 106 participants, of whom 90 (84.9%) were non-ambulatory. The published percentage-change analysis favoured deramiocel, whereas FDA’s analysis using the prespecified plan did not demonstrate a significant difference in the primary endpoint. FDA also identified statistical changes without an updated SAP. The published key secondary LVEF result was not statistically significant. These findings require the analysis scale, analysis population, and statistical plan to remain distinguishable. The Patient Global Impression of Severity confidence interval included no difference. The 12-month controlled comparison and its predominantly non-ambulatory population do not establish effects on long-term survival or applicability across all DMD stages.