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

• ClinicalTrials.gov Identifier: NCT03520036
• Recruitment Status: Completed
• First Posted: May 9, 2018
• Results First Posted: January 20, 2023
• Last Update Posted: January 20, 2023
• Sponsor: Mitsubishi Tanabe Pharma Development America, Inc.
• Information provided by (Responsible Party): Mitsubishi Tanabe Pharma Development America, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Erythropoietic Protoporphyria (EPP)	Drug: MT-7117 low dose; Drug: MT-7117 high dose; Drug: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Erythropoietic Protoporphyria
• Actual Study Start Date: July 5, 2018
• Actual Primary Completion Date: September 28, 2019
• Actual Study Completion Date: September 28, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: MT-7117 low dose	Drug: MT-7117 low dose; MT-7117 low dose QD, oral, 16 weeks
Experimental: MT-7117 high dose	Drug: MT-7117 high dose; MT-7117 high dose QD, oral, 16 weeks
Placebo Comparator: Placebo	Drug: Placebo; Placebo QD, oral, 16 weeks

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: Baseline (Week 0) and 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.
2. 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 [ Time Frame: Baseline (Week 0), and 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.
3. 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 [ Time Frame: Baseline (Week 0), and 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.

Secondary Outcome Measures :

1. Total Number of Sunlight Exposure Episodes With Prodromal Symptoms During 16-Week Double-Blind Treatment Period [ Time Frame: Week 16 ]
2. Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale [ Time Frame: Baseline (Week 0), and Week 16 ]
   The Intensity of Prodromal Symptoms is measured by 11-point Likert scale ranges from 0 (no symptom) to 10 (greatest severity of symptom).
3. Change From Baseline in Average Daily Duration (Minutes) of Prodromal Symptoms at 16-Week Double-Blind Treatment Period [ Time Frame: Baseline (Week 0), and Week 16 ]
4. Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. [ Time Frame: Baseline (Week 0), 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).
5. Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. [ Time Frame: Baseline (Week 0), Week 8, and Week 16 ]
6. Total Number of Pain Events During 16-Week Double-Blind Treatment Period [ Time Frame: Week 16 ]

Other Outcome Measures:

1. Total Number of Sunlight Exposure Episodes [ Time Frame: Baseline (Week 0) and Week 16 ]
2. Change in Pigmentation as Measured by Melanin Density [ Time Frame: Baseline (Week 0) and Week 16 ]
3. The Quality of Life as Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) 57 [ Time Frame: Baseline (Week 0) and Week 16 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

United States, California

ACTCA, A Member of the Alliance, Inc.

Los Angeles, California, United States, 90036

University of California at San Francisco

San Francisco, California, United States, 94143

United States, Florida

University of Miami Miller School of Medicine

Miami, Florida, United States, 33136

United States, Massachusetts

Metro Boston Clinical Partners, LLC

Brighton, Massachusetts, United States, 02135

United States, New York

Ichan School of Medicine at Mount Sinai

New York, New York, United States, 10029

United States, North Carolina

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Remington-Davis, Inc

Columbus, Ohio, United States, 43215

United States, Texas

University of Texas Medical Branch Porphyria Center

Galveston, Texas, United States, 77555

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84108

Sponsors and Collaborators

Mitsubishi Tanabe Pharma Development America, Inc.

Investigators

• Study Director: Head of Clinical Development,; Mitsubishi Tanabe Pharma Development America, Inc.

  Study Documents (Full-Text)

Documents provided by Mitsubishi Tanabe Pharma Development America, Inc.:

Study Protocol  [PDF] August 13, 2019

Statistical Analysis Plan  [PDF] October 15, 2019

More Information

• Responsible Party: Mitsubishi Tanabe Pharma Development America, Inc.
• ClinicalTrials.gov Identifier: NCT03520036
• Other Study ID Numbers: MT-7117-A01
• First Posted: May 9, 2018
• Results First Posted: January 20, 2023
• Last Update Posted: January 20, 2023
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Protoporphyria, Erythropoietic; Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Porphyrias; Metabolic Diseases