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Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)

Phase 3
Recruiting
Conditions
EPP
XLP
Interventions
Registration Number
NCT05005975
Lead Sponsor
Mitsubishi Tanabe Pharma America Inc.
Brief Summary

To evaluate the long-term safety and tolerability of oral dersimelagon.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
301
Inclusion Criteria

Additional screening criteria check may apply for qualification:

    1. Subjects provided written informed consent to participate. For adolescent subjects, both adolescent assent and parental consent will be provided.
    1. Subjects who have completed: MT-7117-G01 (completed through Week 58 [Visit 12]) or, MT-7117-A-302 (completed through Week 58 [Visit 10]) or, MT-7117-A-301 (completed EOT - Week 104 or Week 130) according to protocol amendment 1 or 2.
    1. Subjects are willing and able to travel to the study sites for all scheduled visits.
    1. In the Investigator's opinion, subject can understand the nature of the study and any risks involved in participation, and is willing to cooperate and comply with the protocol restrictions and requirements (including travel).
    1. 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.
    1. Female subjects of childbearing potential and male subjects with partner of childbearing potential must agree to use 2 effective methods of contraception including barrier method (especially for female subjects, one method must be highly effective method)
Exclusion Criteria

Additional screening criteria check may apply for qualification:

A subject will NOT be eligible for this study if ANY of the following criteria apply:

    1. History or presence of photodermatoses other than EPP or XLP.
    1. Presence of clinically significant hepatobiliary disease at Screening, determined as clinically significant by the Investigator.
    1. Subjects with AST, ALT, ALP ≥ 3.0 × upper limit of normal (ULN) or TB > 1.5 × ULN at Screening. The TB level of > 1.5 × ULN listed in this exclusion criteria may not be applicable to subjects with a documented medical history of Gilbert's syndrome. Please consult with the Sponsor for eligibility of subjects with elevated levels due to Gilbert's syndrome.
    1. Subjects with or having a history (in the last 2 years) of excessive alcohol intake in the opinion of the Investigator.
    1. History of melanoma.
    1. 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.
    1. 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.
    1. 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/1.73m2 as calculated by the CKD-EPI creatinine equation (2009) for adults and by the Schwartz creatinine equation for adolescents (2009). MDRD can be used for adults per local recommendations.
    1. 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.
    1. Female subjects who are pregnant, lactating, or intending to become pregnant during the study.
    1. Treatment with phototherapy or afamelanotide within 3 months before baseline (Visit 2 or Re-entry Visit 2).
    1. Treatment with cimetidine or 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 baseline (Visit 2 or Re-entry Visit 2).
    1. Chronic treatment with opioids, ketamine, or medical formulations or derivatives of cannabis within 4 weeks before baseline (Visit 2). Note: This exclusion criterion may not be applicable to subjects at Re-entry Visits. Acute use of scheduled analgesics more than 3 months before baseline (Visit 2) is allowed.
    1. 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.
    1. Previous treatment with any investigational agent other than dersimelagon within 12 weeks before Screening OR 5 half-lives of the investigational product (whichever is longer).
    1. History of any hypersensitivity to the active ingredient and/or excipients (lactose monohydrate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, hypromellose, titanium dioxide, talc, polyethylene glycol, iron oxide yellow, iron oxide red, and iron oxide black).
    1. Subjects who are unable to swallow tablets or have diseases significantly affecting the gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
    1. Using the following drugs (including but not limited to) within 1 week of baseline (Visit 2 or Re-entry Visit 2):

    2. Drugs known to be predominantly metabolized by cytochrome P450 (CYP) 3A4 with a narrow therapeutic index for which elevated plasma concentrations are associated with clinical safety concern or significant medical events.

    3. Drugs that are known substrates of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP)1B1, or OATP1B3 for which elevated plasma concentrations are associated with significant medical events.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Dersimelagon 200mgMT-7117-
Primary Outcome Measures
NameTimeMethod
Number of patients with Treatment emergent adverse events (TEAEs) (including serious adverse events [SAEs] and adverse events of special interest [AESIs]).up to 66 further months

Vital signs (blood pressure, respiratory rate, pulse rate, and body temperature), Clinical laboratory examinations (hematology, coagulation, biochemistry, urinalysis, and others), 12-lead electrocardiogram (ECG) parameters (Mean Heart Rate, PR Interval, QRS Duration, QT interval, QTcB and QTcF) will be assessed.

Number of patients with abnormal Physical examination dataup to 66 further months

Physical examination consists of assessment of abdominal, respiratory, cardiovascular, general appearance, and others.

Number of patients with Nevi appearanceup to 66 further months
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (51)

University of California at San Francisco - CSF Porphyria Center

🇺🇸

San Francisco, California, United States

University Of Miami School Of Medicine, Center For Liver Diseases

🇺🇸

Miami, Florida, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Cleveland Clinic - Taussig Cancer Institute

🇺🇸

Cleveland, Ohio, United States

Einstein Medical Center, Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Wales, Australia

University Multi-Profile Hospital for Active Treatment (UMHAT) St. Ivan Rilski

🇧🇪

Sophia, Belgium

Institute for Clinical and Experimental Medicine - IKEM

🇨🇿

Praha, Czechia

Centre Hospitalier Universitaire de Bordeaux - Hopital Saint - Andre

🇫🇷

Bordeaux, France

Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Louis-Mourier

🇫🇷

Colombes, France

CHU Nantes

🇫🇷

Nantes, France

Hospital Bichat-Hopitaux Universitaires Paris Nord Val de Seine

🇫🇷

Paris, France

Azienda Sanitaria Ospedaliera Santa Croce E Carle - Cuneo

🇮🇹

Cuneo CN, Italy

Ospedalle Galliera

🇮🇹

Genova GE, Italy

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Materno-Infantile - Burlo Garofolo - Clinica Pediatrica

🇮🇹

Trieste TS, Italy

Mazda Hospital of Mazda Motor Corporation

🇯🇵

Hiroshima, Japan

Hamamatsu University Hospital

🇯🇵

Shizuoka, Japan

Erasmus MC, Universitair Medisch Centrum Rotterdam

🇳🇱

Rotterdam, Netherlands

Instytut hematologii i Transfuzjologii

🇵🇱

Warszawa, Poland

Hospital General Universitario De Valencia

🇪🇸

Valencia, Spain

St. John's Institute of Dermatology-Guy's & St Thomas' NHS Foundation Trust

🇬🇧

London, United Kingdom

Southampton General Hospital - University Hospital Southampton NHS Foundation Trust

🇬🇧

Southampton, United Kingdom

Marvel Clinical Research, LLC

🇺🇸

Huntington Beach, California, United States

MetroBoston Clinical Partners, LLC

🇺🇸

Brighton, Massachusetts, United States

Kansas City Research Institute

🇺🇸

Kansas City, Missouri, United States

Icahn School of Medicine at Mount Sinai (ISSMS)-The Mount Sinai Hospital (MSH)

🇺🇸

New York, New York, United States

Wake Forest University Baptist Health

🇺🇸

Winston-Salem, North Carolina, United States

Remington-Davis Clinical Research

🇺🇸

Columbus, Ohio, United States

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

The University of Texas Medical Branch (UTMB)

🇺🇸

Galveston, Texas, United States

University of Washington-Seattle Cancer Care Alliance

🇺🇸

Seattle, Washington, United States

Wesley Medical Research

🇦🇺

Brisbane, Queensland, Australia

Royal Melbourne Hospital (RMH)

🇦🇺

Parkville, Victoria, Australia

University of Alberta Hospital

🇨🇦

Edmonton, Alberta, Canada

Charite - Universitaetsmedizin Berlin

🇩🇪

Berlin, Germany

Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia

🇮🇹

Brescia BS, Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano

🇮🇹

Milan, Italy

U.O.C. Medicina Interna Azienda ospedaliero Universitaria Policlinico di Modena

🇮🇹

Modena, Italy

IFO-San Gallicano IRCCS

🇮🇹

Rome, Italy

Kobe University Hospital

🇯🇵

Kobe, Hyogo, Japan

Sophia Dermatology Clinic

🇯🇵

Kanazawa, Ishikawa, Japan

Osaka Medical College Hospital

🇯🇵

Takatsuki, Osaka, Japan

Tokyo Saiseikai Central Hospital

🇯🇵

Minato-ku, Tokyo, Japan

Toyama University Hospital

🇯🇵

Sugitani, Toyama, Japan

Haukeland University Hospital

🇳🇴

Bergen, Norway

Hospital Clínic de Barcelona

🇪🇸

Barcelona, Spain

Hospital Universitario

🇪🇸

Madrid, Spain

Karolinska University Hospital

🇸🇪

Stockholm, Sweden

Salford Royal NHS Foundation Trust

🇬🇧

Manchester, MN, United Kingdom

Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust

🇬🇧

London, United Kingdom

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