INcreased Sun Exposure Without Pain In Research Participants With EPP or XLP (INSPIRE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Erythropoietic Protoporphyria (EPP); X-Linked Protoporphyria (XLP)
• Intervention / Treatment: Drug: Placebo; Drug: Dersimelagon

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Desk, To prevent mis-communication,; Phone Number: please email:; Email: information@mt-pharma-us.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 02050
      • Not yet recruiting
      • Royal Prince Alfred Hospital
  • Victoria
    • Parkville, Victoria, Australia, 03050
      • Not yet recruiting
      • Royal Melbourne Hospital (RMH)
• Bulgaria
  • Sofia, Bulgaria, 01000
    • Not yet recruiting
    • University Multi-Profile Hospital for Active Treatment (UMHAT) St. Ivan Rilski - Porphyria Center
• Czechia
  • Prague, Czechia, 01958
    • Not yet recruiting
    • Institute for Clinical and Experimental Medicine - IKEM
• France
  • Bordeaux, France, 33000
    • Not yet recruiting
    • Centre Hospitalier Universitaire de Bordeaux - Hopital Saint - Andre
  • Nantes, France, 44000
    • Not yet recruiting
    • CHU Nantes
  • Paris, France, 75018
    • Not yet recruiting
    • Hôpital Bichat - Hospital Bichat-Hopitaux Universitaires Paris Nord Val de Seine
  • Paris, France, 92701
    • Not yet recruiting
    • Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Louis-Mourier
• Italy
  • Brescia, Italy, 25123
    • Not yet recruiting
    • Azienda Ospedaliera Spedali Civili Di Brescia-Universita Degli Studi Di Brescia
  • Cuneo, Italy, 12100
    • Not yet recruiting
    • Azienda Sanitaria Ospedaliera Santa Croce E Carle - Cuneo
  • Genova, Italy, 16128
    • Not yet recruiting
    • Ospedalle Galliera
  • Milan, Italy, 20122
    • Not yet recruiting
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
  • Modena, Italy, 41124
    • Not yet recruiting
    • U.O.C. Medicina Interna Azienda ospedaliero Universitaria Policlinico di Modena
  • Rome, Italy, 00144
    • Not yet recruiting
    • IFO-San Gallicano IRCCS
  • Trieste, Italy, 34137
    • Not yet recruiting
    • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Materno-Infantile - Burlo Garofolo - Clinica Pediatrica
• Japan
  • Tokyo, Japan, 108-0073
    • Not yet recruiting
    • Tokyo Saiseikai Central Hospital
  • Hiroshima-ken
    • Aki-gun, Hiroshima-ken, Japan, 735-8585
      • Not yet recruiting
      • Mazda Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3194
      • Not yet recruiting
      • Hamamatsu University Hospital
• Netherlands
  • Rotterdam, Netherlands, 03015
    • Not yet recruiting
    • Universitair Medisch Centrum Rotterdam
• Poland
  • Warsaw, Poland, 02-776
    • Not yet recruiting
    • Instytut Hematologii i Transfuzjologii
• Spain
  • Madrid, Spain, 28041
    • Not yet recruiting
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46014
    • Not yet recruiting
    • Hospital General Universitario de Valencia
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Not yet recruiting
    • Guy's Hospital
  • Southamption, United Kingdom, SO16 6YD
    • Not yet recruiting
    • Southampton General Hospital - University Hospital Southampton NHS Foundation Trust
• United States
  • California
    • Huntington Beach, California, United States, 92647
      • Recruiting
      • Marvel Clinical Research, LLC
    • San Francisco, California, United States, 94143
      • Not yet recruiting
      • University of California at San Francisco
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University Of Miami School Of Medicine, Center For Liver Diseases
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Not yet recruiting
      • MGH
    • Brighton, Massachusetts, United States, 02135-3511
      • Recruiting
      • MetroBoston Clinical Partners, LLC
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Not yet recruiting
      • Henry Ford Health System
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Recruiting
      • Kansas City Research Institute
  • New York
    • New York, New York, United States, 10029-0311
      • Not yet recruiting
      • Icahn School of Medicine at Mount Sinai (ISMMS) - The Mount Sinai Hospital (MSH)
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Not yet recruiting
      • Wake Forest University Baptist Health
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Recruiting
      • Remington-Davis Clinical Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Not yet recruiting
      • Einstein Medical Center (EMC)
  • Texas
    • Galveston, Texas, United States, 77555-0342
      • Not yet recruiting
      • The University of Texas Medical Branch (UTMB)
  • Washington
    • Seattle, Washington, United States, 98195
      • Not yet recruiting
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Additional screening criteria check may apply for qualification.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: MT-7117	Drug: Dersimelagon; MT-7117

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The comparison between MT-7117 treatment group and placebo group will be performed.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Change (PGIC) at Week 16.	The comparison between MT-7117 treatment group and placebo group will be performed.	Week 16
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.	The comparison between MT-7117 treatment group and placebo group will be performed.	Week 16
Total number of sunlight-induced non-prodrome, phototoxic reactions during the 16-week double-blind treatment period.	The comparison between MT-7117 treatment group and placebo group will be performed.	Week 16

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma America Inc.
• Investigators: Study Director: Head of Medical Science, Mitsubishi Tanabe Pharma America Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2023
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 17, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Skin Diseases; Liver Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Porphyrias, Hepatic; Porphyrias; Genetic Diseases, X-Linked; Protoporphyria, Erythropoietic
• Other Study ID Numbers: MT-7117-A-302; jRCT2031230656 (Registry Identifier: Japan Registry of Clinical Trials (jRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No