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

Официальное название

A Phase 3, Multicenter, Open-label, Long-term, Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)

Обзор

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

Вмешательства

• Препарат MT-7117
  MT-7117

Первичные конечные точки

• Number of patients with Treatment emergent adverse events (TEAEs) (including serious adverse events [SAEs] and adverse events of special interest [AESIs]). [Срок оценки: up to 66 further months]
• Number of patients with abnormal Physical examination data [Срок оценки: up to 66 further months]
• Number of patients with Nevi appearance [Срок оценки: up to 66 further months]

Критерии участия

Критерии включения

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.
• 2\. 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.
• 3\. Subjects are willing and able to travel to the study sites for all scheduled visits.
• 4\. 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).
• 5\. 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.
• 6\. 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)

Критерии исключения

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.
• 2\. Presence of clinically significant hepatobiliary disease at Screening, determined as clinically significant by the Investigator.
• 3\. 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.
• 4\. Subjects with or having a history (in the last 2 years) of excessive alcohol intake in the opinion of the Investigator.
• 5\. History of melanoma.
• 6\. 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.
• 7\. 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.
• 8\. 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.
• 9\. 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.
• 10\. Female subjects who are pregnant, lactating, or intending to become pregnant during the study.
• 11\. Treatment with phototherapy or afamelanotide within 3 months before baseline (Visit 2 or Re-entry Visit 2).
• 12\. 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).
• 13\. 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.
• 14\. 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.
• 15\. 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).
• 16\. 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).
• 17\. 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.
• 18\. Using the following drugs (including but not limited to) within 1 week of baseline (Visit 2 or Re-entry Visit 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 15 центров

• Marvel Clinical Research, LLC — Huntington Beach
• University of California at San Francisco - CSF Porphyria Center — San Francisco
• University Of Miami School Of Medicine, Center For Liver Diseases — Miami
• Massachusetts General Hospital — Boston
• MetroBoston Clinical Partners, LLC — Brighton
• Henry Ford Health System — Detroit
• Kansas City Research Institute — Kansas City
• Icahn School of Medicine at Mount Sinai (ISSMS)-The Mount Sinai Hospital (MSH) — New York
• … и ещё 7 центров

Италия · 7 центров

• Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia — Brescia BS
• Azienda Sanitaria Ospedaliera Santa Croce E Carle - Cuneo — Cuneo CN
• Ospedalle Galliera — Genova GE
• Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano — Milan
• U.O.C. Medicina Interna Azienda ospedaliero Universitaria Policlinico di Modena — Modena
• IFO-San Gallicano IRCCS — Rome
• Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Materno-Infantile - Burlo Garo — Trieste TS

Япония · 7 центров

• Kobe University Hospital — Kobe
• Sophia Dermatology Clinic — Kanazawa
• Osaka Medical College Hospital — Takatsuki
• Tokyo Saiseikai Central Hospital — Minato-ku
• Toyama University Hospital — Sugitani
• Mazda Hospital of Mazda Motor Corporation — Hiroshima
• Hamamatsu University Hospital — Shizuoka

Франция · 4 центра

• Centre Hospitalier Universitaire de Bordeaux - Hopital Saint - Andre — Bordeaux
• Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Louis-Mourier — Colombes
• CHU Nantes — Nantes
• Hospital Bichat-Hopitaux Universitaires Paris Nord Val de Seine — Paris

Великобритания · 4 центра

• Salford Royal NHS Foundation Trust — Manchester
• St. John's Institute of Dermatology-Guy's & St Thomas' NHS Foundation Trust — London
• Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust — London
• Southampton General Hospital - University Hospital Southampton NHS Foundation Trust — Southampton

Австралия · 3 центра

• Royal Prince Alfred Hospital — Camperdown
• Wesley Medical Research — Brisbane
• Royal Melbourne Hospital (RMH) — Parkville

Испания · 3 центра

• Hospital Clínic de Barcelona — Barcelona
• Hospital Universitario — Madrid
• Hospital General Universitario De Valencia — Valencia

Бельгия · 1 центр

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

Канада · 1 центр

• University of Alberta Hospital — Edmonton

Чехия · 1 центр

• Institute for Clinical and Experimental Medicine - IKEM — Prague

Германия · 1 центр

• Charite - Universitaetsmedizin Berlin — Berlin

Нидерланды · 1 центр

• Erasmus MC, Universitair Medisch Centrum Rotterdam — Rotterdam

Норвегия · 1 центр

• Haukeland University Hospital — Bergen

Польша · 1 центр

• Instytut hematologii i Transfuzjologii — Warsaw

Швеция · 1 центр

• Karolinska University Hospital — Stockholm

Идентификаторы

NCT: NCT05005975 · MT-7117-A-301 · jRCT2041210146 · 2021-001831-17

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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