Primary objective

“To investigate the efficacy of MT-7117 on time to onset and severity of first prodromal symptoms (burning, tingling, itching, or stinging) associated with sunlight exposure in adults and adolescents with EPP or XLP.” (opens the source at this quote in a new tab)

Study status and dates

Registry field	Quoted record
Overall status	“Completed”
Start date, actual	“2023-12-11”
Primary completion, actual	“2026-04-14”
Completion, actual	“2026-05-19”
Enrollment, actual	“165”

Sponsor and geographic scope

“The trial, mainly conducted by Tanabe Pharma America, Inc. (Jersey City, New Jersey, USA), enrolled 165 participants with EPP or XLP (aged 12 years and older and under 75 years).” (opens the source at this quote in a new tab)

Posted results

No evidence found.

Randomized, double-blind, placebo-controlled design with open-label extension

“The INSPIRE study is a global, randomized, double-blind, placebo-controlled phase 3 clinical trial in adult and adolescent participants with EPP or XLP. Participants were randomly assigned to either a placebo group or an active treatment group (dersimelagon 200 mg once daily) for a 16-week double-blind period, followed by a 36-week open-label extension period of active treatment.” (opens the source at this quote in a new tab)
“The double-blind treatment phase has been completed, while the open-label phase is ongoing.” (opens the source at this quote in a new tab)

Registry design fields

Design field	Quoted record
Allocation	“Randomized”
Intervention model	“Parallel”
Masking	“Quadruple”
Primary purpose	“treatment”
Phase	“Phase 3”

Diagnosis and age

“Male and female subjects with a confirmed diagnosis of EPP or XLP based on medical history” (opens the source at this quote in a new tab)
“Subjects aged 12 years to 75 years, inclusive, at Screening” (opens the source at this quote in a new tab)
“In the Investigator's opinion, subject can understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the protocol restrictions and requirements (including travel and receiving direct sunlight exposure as much as possible” (opens the source at this quote in a new tab)

Hepatic and dermatologic exclusions

“Presence or history of any hepatobiliary disease, including druginduced liver injury at screening, determined as clinically significant by the Investigator after the discussion with the Sponsor Medical Monitor” (opens the source at this quote in a new tab)
“Subjects with aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≥ 2.0 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN at Screening” (opens the source at this quote in a new tab)
“History of melanoma” (opens the source at this quote in a new tab)

Exclusion of prior dersimelagon and other investigational therapy

“Subjects who participated in any previous MT-7117 clinical studies” (opens the source at this quote in a new tab)
“Previous treatment with any investigational agent such as bitopertin, within 12 weeks before Screening or 5 half-lives of the investigational product (whichever is longer” (opens the source at this quote in a new tab)

Erythrocyte protoporphyrin threshold for entry

No evidence found.

Dose, route, and frequency

“After screening, study participants (ranging from 12 to 75 years of age) received either dersimelagon 200 mg or placebo once daily.” (opens the source at this quote in a new tab)

“The study consists of a 16-week double-blind treatment period, in which participants are randomly assigned to either the placebo group or active treatment group (dersimelagon 200 mg once daily), followed by a 36-week open-label extension period of active treatment.” (opens the source at this quote in a new tab)

Restriction on zinc oxide sunscreen during treatment

“Use of sunscreens with zinc oxide. Note: Sunscreens without zinc oxide are allowed, however their use, in frequency, quantity and body surface area should be maintained relatively stable throughout the duration of the study” (opens the source at this quote in a new tab)

Registered definition of the primary outcome measure

“Change from baseline in average daily sunlight exposure time (minutes) to first prodromal symptom (burning, tingling, itching, or stinging) associated with sunlight exposure between 1 hour post-sunrise and 1 hour pre-sunset at Week 16” (opens the source at this quote in a new tab)
“The comparison between MT-7117 treatment group and placebo group will be performed.” (opens the source at this quote in a new tab)

Registered secondary outcome measures

“Patient Global Impression of Change (PGIC) at Week 16.” (opens the source at this quote in a new tab)
“Total number of sunlight-induced pain events defined as prodromal symptoms (burning, tingling, itching, or stinging) with pain rating of 1-10 on the Likert scale during the 16-week double-blind treatment period.” (opens the source at this quote in a new tab)
“Total number of sunlight-induced non-prodrome, phototoxic reactions during the 16-week double-blind treatment period.” (opens the source at this quote in a new tab)

How participants were instructed to generate the endpoint

“Because of how significant the phototoxic reactions are, we didn't want to ask patients to try to have a phototoxic reaction,” (opens the source at this quote in a new tab)
“But we did ask patients to try to have prodromal symptoms at least once weekly.” (opens the source at this quote in a new tab)

Regulatory precedent for sunlight-exposure time as a clinically meaningful endpoint

“Accurately tracking sunlight exposure is important for evaluating new therapies and pain-free light exposure time is the precedented, clinically meaningful endpoint used to support afamelanotide's marketing authorization in the US and European Union.” (opens the source at this quote in a new tab)

Planned enrollment

“Up to 150 patients with a confirmed diagnosis of EPP or XLP from ages 12 to 75 years may qualify for enrollment.” (opens the source at this quote in a new tab)

Participants randomized per arm

“Yeung and other global INSPIRE trial investigators enrolled 165 patients with EPP or XLP aged 12 years or older. They randomly assigned 82 patients to 200 mg dersimelagon daily and another 83 to placebo. Baseline characteristics were well balanced between groups. Double-blind assessment at week 16 was followed by a 36-week open-label extension.” (opens the source at this quote in a new tab)

Balance of baseline characteristics between arms

“Baseline characteristics were well balanced between groups.” (opens the source at this quote in a new tab)

Tabulated baseline characteristics

No evidence found.

Primary endpoint result

“Dersimelagon, a selective agonist of melanocortin 1 receptor (MC1R), met the primary endpoint, showing a statistically significant prolongation of average daily sunlight exposure time to first prodromal symptom during Weeks 12–16 versus placebo, with a placebo-adjusted least-squares mean difference of 23.19 minutes (p=0.004) in primary analysis. At Week 16, the effect increased to 29.64 minutes (p=0.004) in supplementary analysis.” (opens the source at this quote in a new tab)

Result at the registered Week 16 timepoint

“The primary endpoint was the change from baseline in average daily sunlight exposure time to first prodromal symptom at week 16. The time to prodrome was similar in both groups, Yeung said.” (opens the source at this quote in a new tab)
“During weeks 12-16, there was a statistically significant increase in the average daily time to first prodromal symptom, with a treatment difference of 23 minutes (P = .004).” (opens the source at this quote in a new tab)

Key secondary endpoint results

“Key secondary endpoints were also met, including statistically significant differences in Patient Global Impression of Change (PGIC) and reduction of total pain events compared to placebo (PGIC: -1.83, p<0.001; reduction of total pain events: 39%, p=0.004), supporting clinical meaningful outcome of primary endpoint.” (opens the source at this quote in a new tab)

Responder analyses reported at the congress presentation

“a higher proportion of patients taking dersimelagon reported more than 33 minutes in time to prodrome (P = .04” (opens the source at this quote in a new tab)
“There also was an improvement in the proportion of patients experiencing more than 66 minutes outdoors without prodromal symptoms (P = .12).” (opens the source at this quote in a new tab)
“The study also met a secondary endpoint for the rate of sunlight-induced pain events, which was 39% lower with treatment than with placebo.” (opens the source at this quote in a new tab)

Phototoxic reactions occurring without a preceding prodrome

“The investigators assessed the number of patients who skipped a prodrome and went directly to a full phototoxic reaction, “which is actually pretty rare in EPP,” she added. This outcome was underpowered and there was no statistically significant difference between groups.” (opens the source at this quote in a new tab)

Confidence intervals for the reported effect estimates

No evidence found.

Patient Global Impression of Change

“A higher number of patients on dersimelagon reported “much better” and “moderately better” improvements in symptoms on the Patient Global Impression of Change (PGIC) tool. In the placebo group, patients typically reported “no change” or “a little bit better” symptoms, Yeung said. The difference in PGIC ratings was statistically significant between groups (P< .001).” (opens the source at this quote in a new tab)

Other patient-reported outcome instruments

No evidence found.

Overall tolerability and most common adverse events

“The most common adverse events, occurring more frequently than placebo, were melanocytic nevi (benign moles), headache, nausea, diarrhea, and skin hyperpigmentation, with the mechanism of MC1R agonist.” (opens the source at this quote in a new tab)
“Dersimelagon was generally well-tolerated, with a safety profile consistent with its mechanism of action.” (opens the source at this quote in a new tab)

“In the INSPIRE study, dersimelagon demonstrated a favorable safety and tolerability profile, with most adverse events being mild or moderate in severity.” (opens the source at this quote in a new tab)

Adverse event rates by treatment arm reported at the congress presentation

Adverse event	Dersimelagon 200 mg	Placebo
Headache	“22.0%”	“12.0%”
Melanocytic nevi	“20.7%”	“1.2%”
Nausea	“18.3%”	“10.8%”

Serious adverse event of malignant melanoma in situ

“Safety and tolerability “were quite good,” Yeung said. There were no deaths. There was one serious TEAE in the dersimelagon group — a patient who developed a malignant melanoma in situ. This person had a family history of malignant melanoma and had a lesion at the beginning of the study; the malignant melanoma in situ was identified on day 36.” (opens the source at this quote in a new tab)
“It was determined by the investigator to be related but determined by the sponsor to be unrelated,” (opens the source at this quote in a new tab)

Discontinuations

“In the placebo group, TEAEs that led to discontinuation included brain fog and diarrhea.” (opens the source at this quote in a new tab)
“There was actually one discontinuation in the placebo group and one in the dersimelagon group for hyperpigmentation,” (opens the source at this quote in a new tab)

Cumulative exposure in the development program

“Dersimelagon has been studied in 410 participants with EPP or XLP to date” (opens the source at this quote in a new tab)

Summary: limitations of the INSPIRE evidence base

No results have been posted to ClinicalTrials.gov, the EU Clinical Trials Information System, or the Japan Registry of Clinical Trials, and no peer-reviewed publication exists. No protocol, statistical analysis plan, analysis-set definition, sample-size calculation, or multiplicity strategy is public, and no confidence interval has been published for any endpoint. Disposition, baseline characteristics, and complete adverse event tables are not available, and no results are reported separately for erythropoietic protoporphyria compared with X-linked protoporphyria or for the adolescent subgroup. The company reports the primary analysis over Weeks 12 to 16, whereas the registered primary outcome measure is at Week 16; the presenter reported that time to prodrome was similar between groups at Week 16 alone. Skin pigmentation is a pharmacologic effect of the drug, and in the phase 2 trial most participants correctly identified their assigned treatment, so blinding was incomplete. Participants were required to expose themselves to sunlight until symptoms developed, which may select for less severely affected individuals.

Functional unblinding by treatment-induced pigmentation

“Likewise, in the phase II trial investigating dersimelagon, 97% of the patients in the low dose group, 100% of the patients in the high dose group and 59% of the patients in the placebo group correctly guessed their treatment allocation” (opens the source at this quote in a new tab)
“During the approval procedures of afamelanotide, the EMA assessed that the lack of complete blinding of the trials impaired the validity of the evidence for efficacy, but also acknowledged that there was no possibility of blinding the studies appropriately” (opens the source at this quote in a new tab)

Independent commentary on blinding and selection

“It can be assumed that most patients in the INSPIRE trial did know to which treatment arm they had been randomized to, which might have influenced their sun exposure behavior,” (opens the source at this quote in a new tab)
“The melanocytic nevi rate was 20.7% in the dersimelagon group vs 1.2% in the placebo cohort. This difference “should be closely monitored,” (opens the source at this quote in a new tab)