Clinical trial NCT05005975: Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: EPP
XLP
Lead sponsor: Mitsubishi Tanabe Pharma America Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-16
Enrollment: 301
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.
* 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)

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.
* 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):

  1. 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.
  2. 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.

Primary outcomes:
measure: Number of patients with Treatment emergent adverse events (TEAEs) (including serious adverse events [SAEs] and adverse events of special interest [AESIs]).
timeFrame: up to 66 further months
measure: Number of patients with abnormal Physical examination data
timeFrame: up to 66 further months
measure: Number of patients with Nevi appearance
timeFrame: up to 66 further months
Secondary outcomes:
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Marvel Clinical Research, LLC
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco - CSF Porphyria Center
state: California
city: Miami
country: United States
facility: University Of Miami School Of Medicine, Center For Liver Diseases
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Brighton
country: United States
facility: MetroBoston Clinical Partners, LLC
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai (ISSMS)-The Mount Sinai Hospital (MSH)
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Remington-Davis Clinical Research
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Medical Center, Philadelphia
state: Pennsylvania
city: Galveston
country: United States
facility: The University of Texas Medical Branch (UTMB)
state: Texas
city: Seattle
country: United States
facility: University of Washington-Seattle Cancer Care Alliance
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Wesley Medical Research
state: Queensland
city: Parkville
country: Australia
facility: Royal Melbourne Hospital (RMH)
state: Victoria
city: Sophia
country: Belgium
facility: University Multi-Profile Hospital for Active Treatment (UMHAT) St. Ivan Rilski
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Praha
country: Czechia
facility: Institute for Clinical and Experimental Medicine - IKEM
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hopital Saint - Andre
city: Colombes
country: France
facility: Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Louis-Mourier
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: Hospital Bichat-Hopitaux Universitaires Paris Nord Val de Seine
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin
city: Brescia BS
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
city: Cuneo CN
country: Italy
facility: Azienda Sanitaria Ospedaliera Santa Croce E Carle - Cuneo
city: Genova GE
country: Italy
facility: Ospedalle Galliera
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
city: Modena
country: Italy
facility: U.O.C. Medicina Interna Azienda ospedaliero Universitaria Policlinico di Modena
city: Rome
country: Italy
facility: IFO-San Gallicano IRCCS
city: Trieste TS
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Materno-Infantile - Burlo Garofolo - Clinica Pediatrica
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: Sophia Dermatology Clinic
state: Ishikawa
city: Takatsuki
country: Japan
facility: Osaka Medical College Hospital
state: Osaka
city: Minato-ku
country: Japan
facility: Tokyo Saiseikai Central Hospital
state: Tokyo
city: Sugitani
country: Japan
facility: Toyama University Hospital
state: Toyama
city: Hiroshima
country: Japan
facility: Mazda Hospital of Mazda Motor Corporation
city: Shizuoka
country: Japan
facility: Hamamatsu University Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC, Universitair Medisch Centrum Rotterdam
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Warszawa
country: Poland
facility: Instytut hematologii i Transfuzjologii
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario
city: Valencia
country: Spain
facility: Hospital General Universitario De Valencia
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Manchester
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
state: MN
city: London
country: United Kingdom
facility: St. John's Institute of Dermatology-Guy's & St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital - University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: Mitsubishi Tanabe Pharma America Inc.
name: Head of Medical Science
role: STUDY_DIRECTOR
References: