An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Bitopertin in Participants with Erythropoietic Protoporphyria or X-Linked Protoporphyria

Trial ID: 2025-523275-27-00
Protocol: DISC-1459-501
Sponsor: Disc Medicine Inc.

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Diseases & Conditions

Porphyria non-acute

Objectives

The primary objective of this study is to evaluate the long-term safety and tolerability of bitopertin in individuals diagnosed with erythropoietic protoporphyria or X-linked protoporphyria. The secondary objectives include:

Assessment of long-term efficacy.
Evaluation of changes in protoporphyrin IX concentrations.
Determination of trough plasma concentrations.

Participants

This clinical trial involves a total of 216 participants diagnosed with Erythropoietic Protoporphyria or X-linked protoporphyria. The study population includes both male and female subjects, including vulnerable groups, with an age range starting from 12 years. Selection is limited to individuals who have previously participated in a prior bitopertin study and have completed the randomized treatment phase and the end-of-study visit. Key inclusion requirements include a body weight of at least 32 kg for participants under 18 years of age or a body mass index of at least 18.5 kg/m² for adults. Additionally, participants must utilize highly effective contraception and, for females of childbearing potential, must provide a negative pregnancy test.

Plans and Procedures

This phase 5, open-label, long-term study is designed to evaluate the safety, tolerability, and efficacy of bitopertin in individuals diagnosed with erythropoietic protoporphyria or X-linked protoporphyria. The research methodology focuses on assessing treatment-emergent adverse events, vital signs, physical examinations, and clinical laboratory parameters as primary endpoints. Secondary objectives include measuring changes in daylight tolerance, whole blood metal-free protoporphyrin IX concentrations, and plasma bitopertin levels. Eligible participants must have previously completed a randomized treatment phase and the end-of-study visit of a prior study. The study sequence involves participants who meet specific age, weight, and body mass index requirements. The anticipated duration of the study period extends through late 2028. Early termination from the study may occur based on clinical assessment or non-compliance with study procedures.

Treatment

The experimental treatment consists of bitopertin, administered in the form of a film-coated tablet. The oral dose is 60 mg per administration. This substance is classified as an orphan drug for the management of erythropoietic protoporphyria or X-linked protoporphyria.

Efficacy

The assessment of efficacy in this study involves several secondary endpoints for participants with erythropoietic protoporphyria or X-linked protoporphyria. Evaluation includes the change from baseline in daylight tolerance, measured by the total hours spent in sunlight without pain and the average time to the first prodromal syndrome in sunlight. Additionally, the percent change from baseline in whole blood metal-free protoporphyrin IX concentrations will be determined. Plasma bitopertin concentrations will also be monitored.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Participants with diagnosis of EPP or XLP who are participating (or who have participated) in a prior Disc 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.

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Exclusion Criteria

Participants who have an ongoing serious adverse event (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 or moderate inhibitors or inducers of cytochrome P450 (CYP)3A4 enzymes throughout the study.
Current or planned treatment with antipsychotic medication.
If female, pregnant, planning to become pregnant, or breastfeeding.
Participation in any other clinical protocol or investigational study, other than Disc bitopertin studies, 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.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Recruiting	16 Mar 2026	5
France	Recruiting	16 Mar 2026	12
Germany	Recruiting	16 Mar 2026	10
Ireland	Not Yet Recruiting	16 Mar 2026	1
Italy	Not Yet Recruiting	16 Mar 2026	2
The Netherlands	Recruiting	16 Mar 2026	—
Norway	Not Recruiting	16 Mar 2026	1
Spain	Recruiting	16 Mar 2026	3
Sweden	Not Yet Recruiting	16 Mar 2026	2
Netherlands	—	—	13