Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Erythropoietic Protoporphyria or X-Linked Protoporphyria

EPP Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04402489
• Other study ID #: MT-7117-G01
• Status: Completed
• Phase: Phase 3
• Start date: June 1, 2020
• Est. completion date: July 26, 2022

Study information

• Verified date: May 2023
• Source: Mitsubishi Tanabe Pharma America Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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, or stinging) associated with sunlight exposure in subjects with EPP or XLP aged 12-75.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: July 26, 2022
• Est. primary completion date: December 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

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; and a serum creatinine level of greater than 1.2 mg/dL or an estimated glomerular filtration rate (eGFR) <60 ml/min.

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).

Related Conditions & MeSH terms

• EPP
• XLP

Intervention

Drug:
• Placebo
Placebo
• MT-7117 Low Dose
MT-7117 Low Dose
• MT-7117 High Dose
MT-7117 High Dose

Locations

Country	Name	City	State
Australia	The Wesley Hospital	Brisbane	Queensland
Australia	Royal Melbourne Hospital (RMH)	Melbourne	Victoria
Canada	University of Alberta	Edmonton	Alberta
Germany	Charite - Universitaetsmedizin Berlin	Berlin
Germany	Westfaelische Wilhelms-Universitaet Muenster	Muenster	Northrhein Westalien
Italy	Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia	Brescia
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	I.F.O Hospital Centro Porfirie e Malattie Rare	Rome
Japan	Sophia Dermatology Clinic	Kanazawa	Ishikawa
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	Tokyo Saiseikai Central Hospital	Minato-ku	Tokyo
Japan	Investigator site	Osakasayama	Osaka
Japan	Toyama University Hospital	Sugitani	Toyama
Japan	Osaka Medical College Hospital	Takatsuki	Osaka
Norway	Haukeland University Hospital	Bergen
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Sweden	Karolinska University Hospital	Stockholm
United Kingdom	Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust	London
United Kingdom	University of Manchester	Salford	Manchester
United States	MetroBoston Clinical Partners, LLC	Brighton	Massachusetts
United States	Remington-Davis Clinical Research	Columbus	Ohio
United States	The University of Texas Medical Branch (UTMB)	Galveston	Texas
United States	Marvel Clinical Research, LLC	Huntington Beach	California
United States	Kansas City Research Institute	Kansas City	Missouri
United States	University Of Miami School Of Medicine, Center For Liver Diseases	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai (ISMMS) - The Mount Sinai Hospital (MSH)	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Washington-Seattle Cancer Care Alliance	Seattle	Washington
United States	Wake Forest University Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma America Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Italy,  Japan,  Norway,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline for total score in the domain of pain intensity in the PROMIS-57.	Pain intensity: 0 to 10, where 10 is worst pain imaginable.	Baseline (Week 0) and Week 26
Other	The percentage of subjects who are responders based on average daily sunlight exposure time to first prodromal symptom associated with sunlight exposure between 1 hour post sunrise and 1 hour pre-sunset defined by within-subject meaningful change.		Week 26
Other	Change from baseline for total score in the domain of physical function in the PROMIS-57.	Physical function: 1-5, where 5 is without any difficulty.	Baseline (Week 0) and Week 26
Primary	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.		Baseline (Week 0) and 26 weeks
Secondary	Patient Global Impression of Change (PGIC).	PGIC: Scale from 1 to 7, where 7 is worse.	Week 26
Secondary	Total number of sunlight-induced pain events with pain rating of 1-10 on the Likert scale during the 26-week double-blind treatment period.		Baseline (Week 0) and Week 26