INcreased Sun Exposure Without Pain In Research Subjects With EPP

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Adults and Adolescents With Erythropoietic Protoporphyria or X-Linked Protoporphyria

Conditions
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Erythropoietic Protoporphyria (EPP), X-Linked Protoporphyria (XLP)

Intervention / Treatment
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* Drug: Dersimelagon
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects provided written informed consent to participate. For minor subjects, both minor's assent and parental consent will be required. Male and female subjects with a confirmed diagnosis of EPP or XLP based on medical history. Subjects aged 12 years to 75 years, inclusive, at Screening. Subjects are willing and able to travel to the study sites for all scheduled visits. 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). Female subjects who are non-lactating and have a negative urine pregnancy test at baseline visit prior to receiving the first dose of study drug. Female subjects of childbearing potential and male subjects with partner of child-bearing potential currently using/willing to use 2 effective methods of contraception. Additional screening criteria check may apply for qualification. Exclusion Criteria: History or presence of photodermatoses other than EPP or XLP. Subjects who are unwilling or unable to go outside in sunlight during daylight hours most days (e.g., between 1-hour post-sunrise and 1 hour pre-sunset) during the study. 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. 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. History (in the last 2 years) or presence of alcohol abuse, or abuse of illicit drugs in the opinion of the Investigator. History of melanoma. Presence of squamous cell carcinoma, basal cell carcinoma, or other malignant skin lesions. Any suspicious lesions or nevi will be evaluated. If the suspicious lesion or nevi cannot be resolved through biopsy or excision, the subject will be excluded from the study. History or presence of psychiatric disease judged to be clinically significant by the Investigator and which may interfere with the study evaluation and/or safety of the subjects. Presence of clinically significant acute or chronic renal disease or subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min as calculated by the Chronic Kidney DiseaseEpidemiology Collaboration (CKD-EPI) creatinine equation (2021) for adults and by the Schwartz creatinine equation for adolescents (2009). Modification of Diet in Renal Disease can be used for adults per local recommendations. Presence of any clinically significant disease or laboratory abnormality which, in the opinion of the Investigator, can interfere with the study objectives and/or safety of the subjects. Female subjects who are pregnant, lactating, or intending to become pregnant during the study. Treatment with any of the following medications or therapy within each period before Randomization (Visit 2); Afamelanotide within 3 months Phototherapy within 3 months Cimetidine within 4 weeks Antioxidant agents within 4 weeks, at doses which, in the opinion of the Investigator, may affect study endpoints (including but not limited to beta-carotene, cysteine, pyridoxine). Chronic treatment with any scheduled analgesic agents including, but not limited to, opioids and opioid derivatives such as morphine, hydrocodone, oxycodone, fentanyl, or their combination with other unscheduled analgesics or non-steroidal anti-inflammatory drug (Percocet and Vicodin-like prescription drugs) within 4 weeks. Note: Acute use of scheduled narcotics more than 3 months prior to randomization are allowed. Non-steroidal anti-inflammatory drug, aspirin for analgesia, or prior temporary use of scheduled agents within 3 months of screening is allowed. Dermatological treatments with any drugs or supplements which, in the opinion of the Investigator, can interfere with the objectives of the study or safety of the subjects at screening, such as, for example, tanning agents. Subjects who participated in any previous MT-7117 clinical studies. 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). 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. Additional screening criteria check may apply for qualification.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT-7117<br> | Drug: Dersimelagon<br>* MT-7117<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | The comparison between MT-7117 treatment group and placebo group will be performed. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Change (PGIC) at Week 16. | The comparison between MT-7117 treatment group and placebo group will be performed. | Week 16 | 
| 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. | The comparison between MT-7117 treatment group and placebo group will be performed. | Week 16 | 
| Total number of sunlight-induced non-prodrome, phototoxic reactions during the 16-week double-blind treatment period. | The comparison between MT-7117 treatment group and placebo group will be performed. | Week 16 |