Clinical trial NCT03520036: Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Erythropoietic Protoporphyria
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Erythropoietic Protoporphyria (EPP)
Lead sponsor: Mitsubishi Tanabe Pharma America Inc.
Sponsor class: INDUSTRY
First posted: 2018-05-09
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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).

Primary outcomes:
measure: 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.
timeFrame: Baseline (Week 0) and Week 16
measure: 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
timeFrame: Baseline (Week 0), and Week 16
measure: 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
timeFrame: Baseline (Week 0), and Week 16
Secondary outcomes:
measure: Total Number of Sunlight Exposure Episodes With Prodromal Symptoms During 16-Week Double-Blind Treatment Period
timeFrame: Week 16
measure: Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale
timeFrame: Baseline (Week 0), and Week 16
measure: Change From Baseline in Average Daily Duration (Minutes) of Prodromal Symptoms at 16-Week Double-Blind Treatment Period
timeFrame: Baseline (Week 0), and Week 16
measure: Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16.
timeFrame: Baseline (Week 0), Week 8, and Week 16
measure: Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16.
timeFrame: Baseline (Week 0), Week 8, and Week 16
measure: Total Number of Pain Events During 16-Week Double-Blind Treatment Period
timeFrame: Week 16
Other outcomes:
measure: Total Number of Sunlight Exposure Episodes
timeFrame: Baseline (Week 0) and Week 16
measure: Change in Pigmentation as Measured by Melanin Density
timeFrame: Baseline (Week 0) and Week 16
measure: The Quality of Life as Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) 57
timeFrame: Baseline (Week 0) and Week 16
Locations:
city: Los Angeles
country: United States
facility: ACTCA, A Member of the Alliance, Inc.
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Brighton
country: United States
facility: Metro Boston Clinical Partners, LLC
state: Massachusetts
city: New York
country: United States
facility: Ichan School of Medicine at Mount Sinai
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Remington-Davis, Inc
state: Ohio
city: Galveston
country: United States
facility: University of Texas Medical Branch Porphyria Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Mitsubishi Tanabe Pharma America Inc.
name: Head of Medical Science
role: STUDY_DIRECTOR
References:
citation: Balwani M, Bonkovsky HL, Levy C, Anderson KE, Bissell DM, Parker C, Takahashi F, Desnick RJ, Belongie K; Endeavor Investigators. Dersimelagon in Erythropoietic Protoporphyrias. N Engl J Med. 2023 Apr 13;388(15):1376-1385. doi: 10.1056/NEJMoa2208754.