Clinical trial NCT06144840: INcreased Sun Exposure Without Pain In Research Participants With EPP or XLP
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: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Erythropoietic Protoporphyria (EPP)
X-Linked Protoporphyria (XLP)
Lead sponsor: Mitsubishi Tanabe Pharma America Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-22
Enrollment: 165
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: 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.


Eligibility criteria: Inclusion Criteria:

1. Subjects provided written informed consent to participate. For minor subjects, both minor's assent and parental consent will be required.
2. Male and female subjects with a confirmed diagnosis of EPP or XLP based on medical history.
3. Subjects aged 12 years to 75 years, inclusive, at Screening.
4. Subjects are willing and able to travel to the study sites for all scheduled visits.
5. In the Investigator's opinion, subject can 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 and receiving direct sunlight exposure as much as possible).
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.

Additional screening criteria check may apply for qualification.

Exclusion Criteria:

1. History or presence of photodermatoses other than EPP or XLP.
2. Subjects who are unwilling or unable to go outside in sunlight during daylight hours most days (e.g., between 1-hour post-sunrise and 1 hour pre-sunset) during the study.
3. Presence or history of any hepatobiliary disease, including druginduced liver injury at screening, determined as clinically significant by the Investigator after the discussion with the Sponsor Medical Monitor.
4. Subjects with aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≥ 2.0 × upper limit of normal (ULN) or total bilirubin \>1.5 × ULN at Screening.
5. History (in the last 2 years) or presence of alcohol abuse, or abuse of illicit drugs in the opinion of the Investigator.
6. History of melanoma.
7. 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.
8. 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.
9. Presence of clinically significant acute or chronic renal disease or subjects with an estimated glomerular filtration rate (eGFR) \<60 mL/min as calculated by the Chronic Kidney DiseaseEpidemiology Collaboration (CKD-EPI) creatinine equation (2021) for adults and by the Schwartz creatinine equation for adolescents (2009). Modification of Diet in Renal Disease can be used for adults per local recommendations.
10. 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.
11. Female subjects who are pregnant, lactating, or intending to become pregnant during the study.
12. Treatment with any of the following medications or therapy within each period before Randomization (Visit 2);

    * Afamelanotide within 3 months
    * Phototherapy within 3 months
    * Cimetidine within 4 weeks
    * Antioxidant agents within 4 weeks, 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.

    Note: Acute use of scheduled narcotics more than 3 months prior to randomization are allowed. Non-steroidal anti-inflammatory drug, aspirin for analgesia, or prior temporary use of scheduled agents within 3 months of screening is allowed.
13. Dermatological treatments 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 at screening, such as, for example, tanning agents.
14. Subjects who participated in any previous MT-7117 clinical studies.
15. Previous treatment with any investigational agent such as bitopertin, within 12 weeks before Screening or 5 half-lives of the investigational product (whichever is longer).
16. Use of sunscreens with zinc oxide. Note: Sunscreens without zinc oxide are allowed, however their use, in frequency, quantity and body surface area should be maintained relatively stable throughout the duration of the study.
17. History of any hypersensitivity to the active ingredient and/or excipients (lactose monohydrate, hydroxypropylcellulose, carmellose calcium, magnesium stearate, hypromellose, titanium dioxide, talc, polyethylene glycol, iron oxide yellow, iron oxide red, and iron oxide black). (EU ONLY)
18. 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.(EU ONLY)
19. History of any hypersensitivity to the active ingredient and/or excipients contained in MT-7117 IMP (lactose monohydrate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, hypromellose, titanium dioxide, talc, polyethylene glycol, iron oxide yellow, iron oxide red, and iron oxide black). (UK ONLY)

Additional screening criteria check may apply for qualification.

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 16
timeFrame: Week 16
Secondary outcomes:
measure: Patient Global Impression of Change (PGIC) at Week 16.
timeFrame: Week 16
measure: Total number of sunlight-induced pain events defined as prodromal symptoms (burning, tingling, itching, or stinging) with pain rating of 1-10 on the Likert scale during the 16-week double-blind treatment period.
timeFrame: Week 16
measure: Total number of sunlight-induced non-prodrome, phototoxic reactions during the 16-week double-blind treatment period.
timeFrame: Week 16
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
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: MGH
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 (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: Einstein Medical Center (EMC)
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
state: Washington
city: Parkville
country: Australia
facility: Royal Melbourne Hospital (RMH)
state: Victoria
city: Sofia
country: Bulgaria
facility: University Multi-Profile Hospital for Active Treatment (UMHAT) St. Ivan Rilski - Porphyria Center
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine - IKEM
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hopital Saint - Andre
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: Hôpital Bichat - Hospital Bichat-Hopitaux Universitaires Paris Nord Val de Seine
city: Paris
country: France
facility: Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Louis-Mourier
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
city: Cuneo
country: Italy
facility: Azienda Sanitaria Ospedaliera Santa Croce E Carle - Cuneo
city: Genova
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
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Materno-Infantile - Burlo Garofolo - Clinica Pediatrica
city: Aki-gun
country: Japan
facility: Mazda Hospital
state: Hiroshima-ken
city: Hamamatsu
country: Japan
facility: Hamamatsu University Hospital
state: Shizuoka
city: Tokyo
country: Japan
facility: Tokyo Saiseikai Central Hospital
city: Rotterdam
country: Netherlands
facility: Universitair Medisch Centrum Rotterdam
city: Warsaw
country: Poland
facility: Instytut Hematologii I Transfuzjologii
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital General Universitario De Valencia
city: London
country: United Kingdom
facility: Guy's Hospital
city: Southamption
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: