Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants With EPP

NCT05308472 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: DISC-1459-201
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 9

Brief Summary

This is a Phase 2, multi-center, double-blind, placebo-controlled, parallel group study of bitopertin to evaluate the safety, tolerability, efficacy, and PPIX concentration change in participants with EPP. Participants may roll over to an open label extension portion after completing the double-blind treatment period.

Conditions

Erythropoietic Protoporphyria

Keywords

EPP; DISC-1459; RO4917838; porphyria

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Whole Blood Metal-free PPIX Levels

  Percent change from baseline in PPIX concentration was analyzed using a mixed model repeated measures analysis in the ITT population.

  121 days

Secondary Outcomes (8)

• Total Hours of Sunlight Exposure to Skin on Days With no Pain From 1000 to 1800 Hours (10:00am to 6:00pm)

  121 days

• 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

  121 days

• Total Pain Intensity

  Sum of Day 1 to Day 121

• Incidence of Treatment-emergent Adverse Events

  121 days

• Erythrocyte Total PPIX Concentrations

  121 days

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

DISC-1459 oral dose level 1

EXPERIMENTAL

Drug: DISC-1459

DISC-1459 oral dose level 2

EXPERIMENTAL

Drug: DISC-1459

Interventions

DISC-1459 DRUG

Oral dose level 1, once a day for 120 days

Also known as: Bitopertin, RO4917838

DISC-1459 oral dose level 1

Placebo DRUG

Oral dose, once a day for 120 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older at the time of signing the informed consent form (ICF).
• Diagnosis of EPP, based on medical history by ferrochelatase ( FECH) genotyping or by biochemical porphyrin analysis.
• Body weight ≥50 kg.
• Washout of at least 2 months prior to Screening of afamelanotide and dersimelagon, if applicable.
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) \<2× upper limit of normal (ULN) and total bilirubin \<ULN (unless documented Gilbert syndrome) at Screening. Albumin \>lower limit of normal (LLN).

You may not qualify if:

• Medical History:
• Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
• Other than EPP, an inherited or acquired red cell disease associated with anemia.
• A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug.
• History of liver transplantation.
• History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
• Human immunodeficiency virus (HIV), active Hepatitis B, or C.
• Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgment of the Investigator or Sponsor, would put the participant at unacceptable risk or otherwise preclude the participant from participating in the study
• Condition or concomitant medication that would confound the ability to interpret clinical, clinical laboratory, or participant diary data, including a major psychiatric condition that has had an exacerbation or required hospitalization in the last 6 months.
• Treatment History:
• Concurrent or planned treatment with afamelanotide or dersimelagon during the study period.
• Treatment with opioids for any period \>7 days in the 2 months prior to screening or anticipated to require opioid use for \>7 days at any point during the study.
• New treatment for anemia, including initiation of iron supplementation, in the 2 months prior to Screening.
• Current or planned use of any drugs or herbal remedies known to be strong inhibitors or inducers of CYP3A4 enzymes for 28 days prior to the first dose and throughout the study.
• Hemoglobin \<10 g/dL at Screening.

Sponsors & Collaborators

• Disc Medicine, Inc: lead

Study Sites (9)

University of Alabama Hospital

Birmingham, Alabama, 35233, United States

Location

University of California San Francisco

San Francisco, California, 94117, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157, United States

Location

Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

University of Texas

Galveston, Texas, 77550, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Protoporphyria, Erythropoietic; Porphyrias

Interventions

(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: CMO
• Organization: Disc Medicine

clinicaltrials@discmedicine.com

(617) 674-9274

Study Officials

• Will Savage, MD PhD

  Disc Medicine

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: April 4, 2022
• Study Start: October 31, 2022
• Primary Completion: February 20, 2024
• Study Completion: August 23, 2024
• Last Updated: January 8, 2026
• Results First Posted: January 8, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)