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

Phase 3

Completed

Conditions: EPP
XLP

Interventions: Drug: MT-7117 High Dose
Drug: Placebo
Drug: MT-7117 Low Dose

Registration Number: NCT04402489

Lead Sponsor: Mitsubishi Tanabe Pharma America Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 184

Inclusion Criteria

Subjects provided written informed consent to participate. For minor subjects, both minor assent and parental consent will be provided.
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.
Subjects have a body weight of ≥30 kg.
Subjects are willing and able to travel to the study sites for all scheduled visits.
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).
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 including barrier method as described in the protocol.

Exclusion Criteria

History or presence of photodermatoses other than EPP or XLP.
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.
Presence of clinically significant hepatobiliary disease based on LFT values at Screening.
Subjects with AST, ALT, ALP ≥3.0 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN at Screening.
Subjects with or having a history (in the last 2 years) of excessive alcohol intake in the opinion of the Investigator.
History of melanoma.
Presence of melanoma and/or lesions suspicious for melanoma at Screening.
History of familial melanoma (defined as having 2 or more first-degree relatives, such as parents, sibling and/or child).
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 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.
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 phototherapy within 3 months before Randomization (Visit 2).
Treatment with afamelanotide within 3 months before Randomization (Visit 2).
Treatment with cimetidine within 4 weeks before Randomization (Visit 2).
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).
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.
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.
Previous exposure to MT-7117 (this does not include placebo treated subjects).
Previous treatment with any investigational agent within 12 weeks before Screening OR 5 half-lives of the investigational product (whichever is longer).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MT-7117 High Dose	MT-7117 High Dose	Oral tablet of MT-7117 High Dose once a day.
Placebo Comparator	Placebo	Oral tablet of placebo once a day.
MT-7117 Low Dose	MT-7117 Low Dose	Oral tablet of MT-7117 Low Dose once a day.

Primary Outcome Measures

Name	Time	Method
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 26 (Visit 7)	From 1 hour post-sunrise to 1 hour pre-sunset at Week 26 (Visit 7)

Secondary Outcome Measures

Name	Time	Method
Patient Global Impression of Change (PGIC) at Week 26	Week 26	PGIC: Scale from 1 to 7, where 7 is worse.
Total Number of Sunlight-induced Pain Events Defined as Prodrome Symptoms (Burning, Tingling, Itching, or Stinging) With Pain Rating of 1-10 on the Likert Scale During the 26-week Double-blind Treatment Period.	During the 26-week double-blind treatment period	The Likert scale used ranges from 0 to 10, where 0 indicates the lowest pain rating and 10 indicates the highest pain rating. Likewise, 0 indicates to best outcome and 10 indicates the worst outcome. The sum of the number of pain events with pain rating of 1 to 10 for the day is used as the number of sunlight-induced pain events in the day. The sum of the number of the pain events with pain rating of 1 to 10 in each day during the 26-week Double-blind Treatment Period is calculated as this endpoint.
Change From Baseline for Total Score in the Domain of Pain Intensity in the PROMIS-57 at Week 26	Baseline (Week 0) and Week 26	Pain intensity: 0 to 10, where 10 is worst pain imaginable.
The Percentage of Subjects Who Are Responders	Week 26	The percentage of subjects who are responders based on average daily sunlight exposure time to first prodromal symptom associated with sunlight exposure between 1 hour post-sunrise and 1 hour presunset defined by within-subject meaningful change of 66 minutes increase from baseline to Week 26
Change From Baseline for Total Score in the Domain of Physical Function in the PROMIS-57 at Week 26	Baseline (Week 0) and Week 26	Physical function: 1-5, where 5 is without any difficulty.

Trial Locations

Locations (31): Remington-Davis Clinical Research
🇺🇸
Columbus, Ohio, United States
The University of Texas Medical Branch (UTMB)
🇺🇸
Galveston, Texas, United States
University of Manchester
🇬🇧
Salford, Manchester, United Kingdom
MetroBoston Clinical Partners, LLC
🇺🇸
Brighton, Massachusetts, United States
I.F.O Hospital Centro Porfirie e Malattie Rare
🇮🇹
Rome, Italy
University of Alberta
🇨🇦
Edmonton, Alberta, Canada
Tokyo Saiseikai Central Hospital
🇯🇵
Minato-ku, Tokyo, Japan
The Wesley Hospital
🇦🇺
Brisbane, Queensland, Australia
Charite - Universitaetsmedizin Berlin
🇩🇪
Berlin, Germany
Westfaelische Wilhelms-Universitaet Muenster
🇩🇪
Muenster, Northrhein Westalien, Germany
Royal Melbourne Hospital (RMH)
🇦🇺
Melbourne, Victoria, Australia
U.O.C. Medicina Interna Azienda ospedaliero Universitaria Policlinico di Modena
🇮🇹
Modena, Italy
Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
🇮🇹
Brescia, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
🇮🇹
Milan, Italy
Kobe University Hospital
🇯🇵
Kobe, Hyogo, Japan
Sophia Dermatology Clinic
🇯🇵
Kanazawa, Ishikawa, Japan
University Of Miami School Of Medicine, Center For Liver Diseases
🇺🇸
Miami, Florida, United States
Wake Forest University Baptist Health
🇺🇸
Winston-Salem, North Carolina, United States
Marvel Clinical Research, LLC
🇺🇸
Huntington Beach, California, United States
Kansas City Research Institute
🇺🇸
Kansas City, Missouri, United States
Icahn School of Medicine at Mount Sinai (ISMMS) - The Mount Sinai Hospital (MSH)
🇺🇸
New York, New York, United States
University of Washington-Seattle Cancer Care Alliance
🇺🇸
Seattle, Washington, United States
Osaka Medical College Hospital
🇯🇵
Takatsuki, Osaka, Japan
Investigator site
🇯🇵
Osakasayama, Osaka, Japan
Toyama University Hospital
🇯🇵
Sugitani, Toyama, Japan
Hospital Clínic de Barcelona
🇪🇸
Barcelona, Spain
Haukeland University Hospital
🇳🇴
Bergen, Norway
Karolinska University Hospital
🇸🇪
Stockholm, Sweden
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust
🇬🇧
London, United Kingdom
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States