Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Erythropoietic Protoporphyria

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of MT-7117 on sunlight exposure duration without symptoms and tolerance in subjects with EPP.

Detailed Description
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This is a Phase 2, randomized, double-blind, placebo controlled study to assess the efficacy, tolerability, and safety of MT-7117 in subjects with EPP. The study consists of a 2 week screening period, a 16 week double-blind treatment period, and a 6 week follow-up period at Week 22. The total participation period is approximately 24 weeks.

Official Title
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A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Erythropoietic Protoporphyria

Conditions
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Erythropoietic Protoporphyria (EPP)

Intervention / Treatment
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* Drug: MT-7117 low dose
* Drug: MT-7117 high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Additional screening criteria check may apply for qualification. Inclusion Criteria: 1. Subjects provided written informed consent to participate. 2. Male and female subjects with a confirmed diagnosis of EPP based on medical history, aged 18 years to 75 years, inclusive, at Screening. 3. Subjects are willing and able to travel to the study sites for all scheduled visits. 4. In the Investigator's opinion, subject is able to 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). Exclusion Criteria: 1. History or presence of photodermatoses other than EPP. 2. Subjects who are unwilling or unable to go outside during daylight hours (e.g., between 1 hour post sunrise and 1 hour pre-sunset) during the study. 3. Presence of clinically significant hepatobiliary disease based on LFT values at Screening. 4. Subjects with AST, ALT, ALP ≥3.0 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN at Screening. 5. Subjects with or having a history (in the last 2 years) of excessive alcohol intake in the opinion of the Investigator. 6. History or presence of melanoma and/or atypical nevus at Screening. 7. History of familial melanoma (defined as having 2 or more first-degree relatives, such as parents, sibling and/or child). 8. History or presence of pre-malignant skin lesion squamous cell carcinoma, basal cell carcinoma, or other malignant skin lesions. 9. 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. 10. Presence of clinically significant acute or chronic renal disease based upon the subject's medical records including hemodialysis; and a serum creatinine level of greater than 1.2 mg/dL or a glomerular filtration rate (GFR) <60 ml/min. 11. 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. 12. Pregnancy or lactation. 13. Females of child bearing potential and male subjects with partners of child-bearing potential unwilling to use adequate contraception measures as described in the protocol. 14. Treatment with phototherapy within 3 months before Randomization (Visit 2). 15. Treatment with afamelanotide within 3 months before Randomization (Visit 2). 16. Treatment with cimetidine within 4 weeks before Randomization (Visit 2). 17. Treatment with antioxidant agents at doses which, in the opinion of the Investigator, may affect study endpoints (including but not limited to beta-carotene, cysteine, pyridoxine) within 4 weeks before Randomization (Visit 2). 18. Chronic treatment with prescription-based analgesic agents including but not limited to opioids and opioid derivatives such as morphine, hydrocodone, oxycodone or their combination with other analgesics or non-steroidal anti-inflammatory drug (NSAID, as Percocet and Vicodin-like prescription drugs) within 4 weeks before Randomization (Visit 2). 19. Treatment 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. 20. Previous exposure to MT 7117. 21. Previous treatment with any investigational agent within 12 weeks before Screening OR 5 half-lives of the investigational product (whichever is longer).

Ages Eligible for Study
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Minimum Age: 18 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 low dose<br> | Drug: MT-7117 low dose<br>* MT-7117 low dose QD, oral, 16 weeks<br>|
| Experimental: MT-7117 high dose<br> | Drug: MT-7117 high dose<br>* MT-7117 high dose QD, oral, 16 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo QD, oral, 16 weeks<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 Time (Minutes) to First Prodromal Symptom Associated With Sunlight Exposure Between Hour Post Sunrise and 1 Hour Pre-Sunset at Week 16. | Duration in minutes, of sunlight exposure between 1 hour post sunrise and 1 hour pre-sunset. The average Duration in minutes, of sunlight exposure before the first prodromal symptom between 1 hour post sunrise and 1 hour pre-sunset. The average duration means that average of daily durations in 14-day windows before Day 1 (or week 16 Day) applied. | Baseline (Week 0) and Week 16 | 
| Change From Baseline in Average Daily Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | Change from baseline to week 16 in Average Daily Duration (Minutes) of Sunlight Exposure sums any sunlight exposure time excluding any overlapped time with prodromal symptoms, including if the patients go out multiple times on the same day after the prodromal symptom had previously ended. | Baseline (Week 0), and Week 16 | 
| Change From Baseline in Average Daily Mean Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | Change from baseline to week 16 in Average Daily Mean Duration (Minutes) of Sunlight Exposure without prodromal symptoms divided by the number of sunlight exposures periods applicable that day. | Baseline (Week 0), and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Sunlight Exposure Episodes With Prodromal Symptoms During 16-Week Double-Blind Treatment Period |  | Week 16 | 
| Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale | The Intensity of Prodromal Symptoms is measured by 11-point Likert scale ranges from 0 (no symptom) to 10 (greatest severity of symptom). | Baseline (Week 0), and Week 16 | 
| Change From Baseline in Average Daily Duration (Minutes) of Prodromal Symptoms at 16-Week Double-Blind Treatment Period |  | Baseline (Week 0), and Week 16 | 
| Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Pigmentation will be assessed in melanin density which are numeric scores measured by spectrophotometer on 6 skin segments (forehead, left cheek, right inside upper arm, left medial forearm, right-hand side of abdomen, and left-hand side of buttock). | Baseline (Week 0), Week 8, and Week 16 | 
| Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. |  | Baseline (Week 0), Week 8, and Week 16 | 
| Total Number of Pain Events During 16-Week Double-Blind Treatment Period |  | Week 16 |