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

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

The primary objective of this study is 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 aged 12-75.

Additional screening criteria check may apply for qualification.

Inclusion Criteria:

1. Subjects provided written informed consent to participate. For minor subjects, both minor assent and parental consent will be provided.
2. Male and female subjects with a confirmed diagnosis of EPP or XLP based on medical history, aged 12 years to 75 years, inclusive, at Screening.
3. Subjects have a body weight of ≥30 kg.
4. Subjects are willing and able to travel to the study sites for all scheduled visits.
5. 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).
6. 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.
7. Female subjects of childbearing potential and male subjects with partner of child-bearing potential currently using/willing to use 2 effective methods of contraception including barrier method as described in the protocol.

Exclusion Criteria:

1. History or presence of photodermatoses other than EPP or XLP.

2. Subjects who are unwilling or unable to go outside during daylight hours most days (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 of melanoma.

7. Presence of melanoma and/or lesions suspicious for melanoma at Screening.

8. History of familial melanoma (defined as having 2 or more first-degree relatives, such as parents, sibling and/or child).

9. 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.

10. 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.

11. Presence of clinically significant acute or chronic renal disease based upon the subject's medical records including hemodialysis; an estimated glomerular filtration rate (eGFR) <60 mL/min as calculated by the Chronic Kidney Disease-Epidemiology Collaboration (CKDEPI) creatinine equation (2009) for adults and by the Schwartz creatinine equation for adolescents (2009). Modification of Diet in Renal Disease (MDRD) can be used for adults per local recommendations.

12. 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.

13. Female subjects who are pregnant, lactating, or intending to become pregnant during the study.

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 within 4 weeks before Randomization (Visit 2), at doses which, in the opinion of the Investigator, may affect study endpoints (including but not limited to beta-carotene, cysteine, pyridoxine).

18. 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 before Randomization (Visit 2).

    Acute use of scheduled narcotics greater than 3 months prior to randomization, OTCs, such as NSAIDs or aspirin for analgesia, or prior temporary use of scheduled agents within 3 months of screening are not excluded.

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 (this does not include placebo treated subjects).

21. Previous treatment with any investigational agent within 12 weeks before Screening OR 5 half-lives of the investigational product (whichever is longer).