HELIOS: Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP or XLP

NCT05883748 | Enrolling By Invitation Phase 2 FDA Drug

• 1 other identifier: DISC-1459-501
• Study Type: interventional
• Target: 230
• Locations: 2 countries
• Sites: 13

Brief Summary

This is an open-label, long-term extension study to investigate the safety, tolerability and efficacy of DISC-1459 in participants with EPP.

Conditions

Erythropoietic Protoporphyria

Keywords

EPP; DISC-1459; porphyria; RO4917838

Outcome Measures

Primary Outcomes (6)

• Incidence of treatment-emergent adverse events

  up to 5 Years

• Incidence of clinically abnormal vital signs

  up to 5 Years

• Incidence of clinically abnormal physical exam

  up to 5 Years

• Incidence of abnormal laboratory test results

  up to 5 Years

• Assessment of Patient Health Questionnaire (PHQ-8)

  The Patient Health Questionnaire (PHQ-8), an 8-item participant-report measure for screening for depression and for establishing depression severity. The total score ranges from 0-24, with a higher score indicating greater depression symptom severity.

  up to 5 Years

• Assessment of C-SSRS

  The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies.

  up to 5 Years

Secondary Outcomes (3)

• Change from baseline in daily daylight tolerance, as assessed by total hours spent in the sunlight without pain and average time to first prodromal syndrome in sunlight

  up to 5 Years

• Change from baseline in whole blood metal-free PPIX levels

  up to 5 Years

• Plasma Bitopertin Concentrations

  up to 5 Years

Study Arms (2)

DISC-1459 Oral Dose Level 1

EXPERIMENTAL

Oral dose, once a day

Drug: DISC-1459

DISC-1459 Oral Dose Level 2

EXPERIMENTAL

Oral dose, once a day

Drug: DISC-1459

Interventions

DISC-1459 DRUG

DISC-1459 dose level 1

Also known as: Bitopertin, RO4917838

DISC-1459 Oral Dose Level 1

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with diagnosis of EPP who are participating (or who have participated) in a prior Disc Medicine bitopertin study and who have completed the randomized treatment phase and End-of-Study visit
• Aged ≥12 years upon study consent
• Body weight ≥32 kg for participants \<18 years of age and BMI ≥18.5 kg/m2 for adult participants
• Willing to practice highly effective methods of birth control (both males who have partners of childbearing potential and females of childbearing potential during the study, while taking study drug, and for at least 30 days after the last dose of study drug.
• Negative urine or serum pregnancy test (females of childbearing potential).
• Able to understand the study aims, procedures, and requirements, and provide written informed consent (and assent if necessary).
• Able to comply with all study procedures.

You may not qualify if:

• Participants who have an ongoing SAE from a clinical study that is assessed by the investigator as related to bitopertin
• Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgement of the Investigator or Sponsor, would put the participant at unacceptable risk or otherwise preclude participation 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
• Planned treatment with afamelanotide or dersimelagon during the study
• Planned use of any drugs or herbal remedies known to be strong inhibitors or inducers of cytochrome p450 (CYP)3A4 enzymes throughout the study
• If female, pregnant, or breastfeeding
• Participation in any other clinical protocol or investigational trial, other than Disc Medicine bitopertin trials, that involves administration of experimental therapy and/or therapeutic devices within 30 days of Day 1
• Score of PHQ-8 ≥10 at screening or imminent suicidal risk identified by the C-SSRS as defined as suicidal ideation with intent (Grade 4 or 5) within the last year or any suicidal behavior within the last 5 years.
• Consumption of grapefruit/Seville orange and products containing these for 14 days prior to first dose of study drug and throughout the study

Sponsors & Collaborators

• Disc Medicine, Inc: lead

Study Sites (13)

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

MetroBoston Clinical Partners

Boston, Massachusetts, 02135, 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

Remington-Davis Clinical Research

Columbus, Ohio, 43215, 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

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

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

Study Officials

• Will Savage, MD PhD

  Disc Medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: June 1, 2023
• Study Start: August 31, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); US (11)