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

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

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

Study Overview

• Status: Enrolling by invitation
• Conditions: Erythropoietic Protoporphyria
• Intervention / Treatment: Drug: DISC-1459; Drug: DISC-1459

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• France
  • France
    • Nantes, France, France, 44093
      • CHU de Nantes - Hôtel Dieu, Service de dermatologie
    • Paris, France, France, 75018
      • Centre d'Investigation Clinique (CIC) Hôpital Bichat - Claude-Bernard
• Germany
  • Germany
    • Berlin, Germany, Germany, 12203
      • Charité - Universitätsmedizin Berlin, Institute of Allergology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Hospital
  • California
    • San Francisco, California, United States, 94117
      • University of California San Francisco
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02135
      • MetroBoston Clinical Partners
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Atrium Health Wake Forest Baptist
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington-Davis Clinical Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center
  • Texas
    • Galveston, Texas, United States, 77550
      • University of Texas
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DISC-1459 Oral Dose Level 1; Oral dose, once a day	Drug: DISC-1459; DISC-1459 dose level 1; Other Names: Bitopertin; RO4917838; Drug: DISC-1459; DISC-1459 dose level 2; Other Names: Bitopertin; RO4917838
Experimental: DISC-1459 Oral Dose Level 2; Oral dose, once a day	Drug: DISC-1459; DISC-1459 dose level 1; Other Names: Bitopertin; RO4917838; Drug: DISC-1459; DISC-1459 dose level 2; Other Names: Bitopertin; RO4917838

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Disc Medicine, Inc
• Investigators: Study Director: Will Savage, MD PhD, Disc Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: EPP; porphyria; DISC-1459; RO4917838
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Skin Diseases; Skin Diseases, Genetic; Porphyrias, Hepatic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Protoporphyria, Erythropoietic; Porphyrias; (4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone
• Other Study ID Numbers: DISC-1459-501

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
• product manufactured in and exported from the U.S.: No