Study of Bitopertin in Participants With EPP or XLP (APOLLO) (APOLLO)

APOLLO: A Randomized, Double-Blind, Placebo-Controlled Study of Bitopertin to Evaluate the Efficacy, Safety, and Tolerability in Participants With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)

The goal of this clinical trial is to learn if bitopertin works and is safe to treat EPP or XLP in participants 12 years or older. The main questions it aims to answer are:

• Whether bitopertin increases pain-free sunlight exposure after 6 months of treatment in participants with EPP or XLP.
• How PPIX concentration levels change from before bitopertin treatment to after 6 months of treatment.

Researchers will compare bitopertin to a placebo look-alike substance that contains no drug.

Participants will complete daily questionnaires and attend study visits for assessments.

Study Overview

• Status: Active, not recruiting
• Conditions: Erythropoietic Protoporphyria (EPP); X-Linked Protoporphyria (XLP)
• Intervention / Treatment: Drug: Placebo; Drug: DISC-1459

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: 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
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R3
      • University of Alberta
• 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
  • Saxony
    • Chemnitz, Saxony, Germany, 09116
      • Klinikum Chemnitz Ggmbh
• Ireland
  • Dublin, Ireland, D12N512
    • Children's Health Ireland (CHI)
• Italy
  • Roma, Italy, 53-00144
    • Instituto Dermatologico San Gallicano Istituti Fisioterapici Ospitalieri IRCCS
• Netherlands
  • The Netherlands
    • Rotterdam, The Netherlands, Netherlands, 3015 GD
      • Erasmus MC
• Spain
  • Spain
    • Barcelona, Spain, Spain, 08036
      • Hospital Clinic De Barcelona
• Sweden
  • Sweden
    • Stockholm, Sweden, Sweden, 141 86
      • Karolinska University Hospital
• United Kingdom
  • Salford, United Kingdom, M6 8HD
    • Photobiology Unit, Salford Royal Hospital
  • England
    • London, England, United Kingdom, SE1 9RT
      • Guy's and St Thomas' NHS Foundation Trust
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Clinical Research Centre, Ninewells Hospital & Medical School , NHS Tayside
• United States
  • California
    • Huntington Beach, California, United States, 92647
      • Marvel Clinical Research
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Florida
    • Miami, Florida, United States, 33146
      • University of Miami Miller School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02135
      • MetroBoston Clinical Partners
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington-Davis Clinical Research
  • Texas
    • Galveston, Texas, United States, 77550
      • University of Texas Medical Branch
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged 12 years or older at the time of study consent.
2. Diagnosis of EPP or XLP, based on medical history by ferrochelatase (FECH) or aminolevulinic acid synthase 2 (ALAS2) genotyping or by biochemical porphyrin analysis.
3. Minimum daily Sun Exposure Diary compliance ≥85% on Days -14 through Day -1, inclusive, during screening, and at least 1 successfully completed Sun Exposure Challenge (adults only, as this assessment is optional for adolescents) or historical recall of time to prodrome
4. Body weight ≥32 kg (ages 12 to <18 years), body mass index ≥18.5 kg/m2 (ages ≥18 years) at screening.
5. Washout of at least 2 months prior to screening of afamelanotide and dersimelagon, if applicable.
6. Aspartate aminotransferase and alanine transaminase <3× upper limit of normal (ULN)and total bilirubin <2× ULN (unless documented Gilbert syndrome) at screening. Albumin >lower limit of normal (LLN).
7. Willing to practice highly effective methods of birth control (both males who have partners of childbearing potential and females of childbearing potential during screening, while taking study drug, and for at least 30 days after the last dose of study drug).

Exclusion Criteria:

1. Major surgery within 8 weeks before screening or incomplete recovery from any previous surgery.
2. Other than EPP or XLP, an inherited intrinsic or extrinsic red cell disease associated with anemia.
3. Known hypersensitivity to any component of the study drug.
4. History of liver transplantation or anticipated need for liver transplantation.
5. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
6. Active human immunodeficiency virus (HIV), active hepatitis B or C.
7. 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.

8. 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:

9. Prior exposure to bitopertin.
10. Concurrent or planned treatment with afamelanotide or dersimelagon during the study period.
11. 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.
12. New treatment for anemia, including initiation of iron supplementation, within 1 month of screening.
13. Current or planned use of any drugs or herbal remedies known to be strong or moderate inhibitors or inducers of cytochrome P450 (CYP)3A4 enzymes for 28 days prior to the first dose and throughout the study.

14. Current or planned treatment with antipsychotic medication.

    Laboratory Exclusions:

15. Hemoglobin <10 g/dL at screening.

    Miscellaneous:

16. Participation in other interventional clinical studies within 30 days prior to screening.
17. If female, pregnant or breastfeeding.

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; Oral dose, once a day for 24 weeks
Experimental: DISC-1459 oral dose	Drug: DISC-1459; Oral dose, once a day for 24 weeks; Other Names: Bitopertin; RO4917838

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Average monthly total time in sunlight on days without pain from a phototoxic reaction between 10:00 to 18:00 (10:00 AM to 6:00 PM) after 6 months (24 weeks) of treatment	24 weeks
Percent change from baseline in whole-blood metal-free PPIX levels at 6 months	24 weeks
Safety and tolerability, as assessed by adverse events (AEs) and laboratory results, over the 6-month treatment period	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Occurrence of phototoxic reactions over the 6-month treatment period	24 weeks
Cumulative total time in sunlight on days without pain from a phototoxic reaction between 10:00 to 18:00 (10:00 AM to 6:00 PM) over the 6-month (24-week) treatment period	24 weeks
Change from baseline in 2-week average daily sunlight exposure time (minutes) to first prodromal symptom (eg, burning, tingling, itching, or stinging) associated with sunlight exposure between 1 hour post-sunrise and 1 hour pre-sunset at 6 months	24 weeks

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): April 4, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: EPP; XLP; 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; Protoporphyria, Erythropoietic, X-Linked Dominant; Substandard Drugs; Pharmaceutical Preparations; (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-1459-301; 2024-520407-27-00 (Ctis)

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