Clinical trial NCT04402489: Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Erythropoietic Protoporphyria or X-Linked Protoporphyria
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Adults and Adolescents With Erythropoietic Protoporphyria or X-Linked Protoporphyria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: EPP
XLP
Lead sponsor: Mitsubishi Tanabe Pharma America Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-26
Enrollment: 184
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Additional screening criteria check may apply for qualification.

Inclusion Criteria:

1. Subjects provided written informed consent to participate. For minor subjects, both minor assent and parental consent will be provided.
2. 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.
3. Subjects have a body weight of ≥30 kg.
4. Subjects are willing and able to travel to the study sites for all scheduled visits.
5. 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).
6. 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.
7. 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:

1. History or presence of photodermatoses other than EPP or XLP.
2. 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.
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 of melanoma.
7. Presence of melanoma and/or lesions suspicious for melanoma at Screening.
8. History of familial melanoma (defined as having 2 or more first-degree relatives, such as parents, sibling and/or child).
9. 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.
10. 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.
11. 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.
12. 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.
13. Female subjects who are pregnant, lactating, or intending to become pregnant during the study.
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 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).
18. 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.
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 (this does not include placebo treated subjects).
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 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)
timeFrame: From 1 hour post-sunrise to 1 hour pre-sunset at Week 26 (Visit 7)
Secondary outcomes:
measure: Patient Global Impression of Change (PGIC) at Week 26
timeFrame: Week 26
measure: 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.
timeFrame: During the 26-week double-blind treatment period
measure: Change From Baseline for Total Score in the Domain of Pain Intensity in the PROMIS-57 at Week 26
timeFrame: Baseline (Week 0) and Week 26
measure: The Percentage of Subjects Who Are Responders
timeFrame: Week 26
measure: Change From Baseline for Total Score in the Domain of Physical Function in the PROMIS-57 at Week 26
timeFrame: Baseline (Week 0) and Week 26
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Marvel Clinical Research, LLC
state: California
city: Miami
country: United States
facility: University Of Miami School Of Medicine, Center For Liver Diseases
state: Florida
city: Brighton
country: United States
facility: MetroBoston Clinical Partners, LLC
state: Massachusetts
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 (ISMMS) - The Mount Sinai Hospital (MSH)
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Health
state: North Carolina
city: Columbus
country: United States
facility: Remington-Davis Clinical Research
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
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: Brisbane
country: Australia
facility: The Wesley Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital (RMH)
state: Victoria
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Muenster
country: Germany
facility: Westfaelische Wilhelms-Universitaet Muenster
state: Northrhein Westalien
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
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: I.F.O Hospital Centro Porfirie e Malattie Rare
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: Sophia Dermatology Clinic
state: Ishikawa
city: Osakasayama
country: Japan
facility: Investigator site
state: Osaka
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: Bergen
country: Norway
facility: Haukeland University Hospital
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Salford
country: United Kingdom
facility: University of Manchester
state: Manchester
city: London
country: United Kingdom
facility: Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust
Study officials:
affiliation: Mitsubishi Tanabe Pharma America Inc.
name: Head of Medical Science
role: STUDY_DIRECTOR
References: