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

NCT06910358 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DISC-1459-3012024-520407-27-00
• Study Type: interventional
• Target: 183
• Locations: 12 countries
• Sites: 27

Brief Summary

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.

Conditions

Erythropoietic Protoporphyria (EPP); X-Linked Protoporphyria (XLP)

Keywords

EPP; XLP; DISC-1459; RO4917838; porphyria

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

DISC-1459 oral dose

EXPERIMENTAL

Drug: DISC-1459

Interventions

DISC-1459 DRUG

Oral dose, once a day for 24 weeks

Also known as: Bitopertin, RO4917838

DISC-1459 oral dose

Placebo DRUG

Oral dose, once a day for 24 weeks

Placebo

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:

• Aged 12 years or older at the time of study consent.
• Diagnosis of EPP or XLP, based on medical history by ferrochelatase (FECH) or aminolevulinic acid synthase 2 (ALAS2) genotyping or by biochemical porphyrin analysis.
• 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
• Body weight ≥32 kg (ages 12 to \<18 years), body mass index ≥18.5 kg/m2 (ages ≥18 years) at screening.
• Washout of at least 2 months prior to screening of afamelanotide and dersimelagon, if applicable.
• 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).
• 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).

You may not qualify if:

• Major surgery within 8 weeks before screening or incomplete recovery from any previous surgery.
• Other than EPP or XLP, an inherited intrinsic or extrinsic red cell disease associated with anemia.
• Known hypersensitivity to any component of the study drug.
• History of liver transplantation or anticipated need for liver transplantation.
• History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
• Active 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:
• Prior exposure to bitopertin.
• 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, within 1 month of screening.
• 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.
• Current or planned treatment with antipsychotic medication.

Sponsors & Collaborators

• Disc Medicine, Inc: lead

Study Sites (27)

Marvel Clinical Research

Huntington Beach, California, 92647, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33146, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

MetroBoston Clinical Partners

Boston, Massachusetts, 02135, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Remington-Davis Clinical Research

Columbus, Ohio, 43215, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77550, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

UZ Leuven

Leuven, 3000, Belgium

Location

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

CHU de Nantes - Hôtel Dieu, Service de dermatologie

Nantes, France, 44093, France

Location

Centre d'Investigation Clinique (CIC) Hôpital Bichat - Claude-Bernard

Paris, France, 75018, France

Location

Charité - Universitätsmedizin Berlin, Institute of Allergology

Berlin, Germany, 12203, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, Saxony, 09116, Germany

Location

Children's Health Ireland (CHI)

Dublin, D12N512, Ireland

Location

Instituto Dermatologico San Gallicano Istituti Fisioterapici Ospitalieri IRCCS

Roma, 53-00144, Italy

Location

Erasmus MC

Rotterdam, The Netherlands, 3015 GD, Netherlands

Location

Hospital Clinic de Barcelona

Barcelona, Spain, 08036, Spain

Location

Karolinska University Hospital

Stockholm, Sweden, 141 86, Sweden

Location

Guy's and St Thomas' NHS Foundation Trust

London, England, SE1 9RT, United Kingdom

Location

Clinical Research Centre, Ninewells Hospital & Medical School , NHS Tayside

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Photobiology Unit, Salford Royal Hospital

Salford, M6 8HD, United Kingdom

Location

MeSH Terms

Conditions

Protoporphyria, Erythropoietic; Protoporphyria, Erythropoietic, X-Linked Dominant; 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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: April 4, 2025
• Study Start: April 4, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); US (11); FR (2); AU (2); IE (1); ES (1); BE (1); SE (1); GB (3); CA (1); DE (2); NL (1)