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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Disc Medicine Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

23 Oct 2025 → ongoing

Decision date (initial)

2025-10-01

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Disc Medicine, Inc.

External identifiers

EU CT number

2024-520407-27-00

WHO UTN

U1111-1319-3826

ClinicalTrials.gov

NCT06910358

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacodynamic, Safety, Others, Pharmacokinetic

• To assess average pain-free sunlight exposure tolerance after 6 months of treatment
• To assess changes in whole-blood metal-free protoporphyrin IX (PPIX) levels after 6 months of treatment
• To assess safety and tolerability

Secondary objectives 4

1. To assess the occurrence of phototoxic reactions
2. To assess cumulative total pain-free sunlight exposure over 6 months of treatment
3. To assess changes in time to prodromal symptoms
4. Further Objectives (exploratory) are visible in the study protocol

Conditions and MedDRA coding

X-Linked Protoporphyria (XLP)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, U.S. Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-000439-PIP03-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Aged 12 years or older at the time of study consent.
2. 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. 3. Minimum daily Sun Exposure Diary compliance ≥85% on Days [CCI] through Day [CCI], 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. 4. Body weight ≥32 kg (ages 12 to <18 years), body mass index ≥18.5 kg/m2 (ages ≥18 years) at screening.
5. 5. Washout of at least 2 months prior to screening of afamelanotide and dersimelagon, if applicable.
6. 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. 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.
8. 8. Negative pregnancy test (females of childbearing potential) at screening (Days [CCI] to [CCI]) AND baseline (Day 1), prior to dosing.
9. 9. Able to understand the study aims, procedures, and requirements, and provide written informed consent (and assent if necessary).
10. 10. Able to comply with all study procedures.

Exclusion criteria 18

1. 1. Major surgery within 8 weeks before screening or incomplete recovery from any previous surgery.
2. 2. Other than EPP or XLP, an inherited intrinsic or extrinsic red cell disease associated with anemia, eg, G6PD, hemoglobinopathy, membranopathy, or immune or nonimmune hemolytic anemia. Any comorbid hematologic disease must be deemed acceptable by the Sponsor.
3. 3. Known hypersensitivity to any component of the study drug.
4. 4. History of liver transplantation or anticipated need for liver transplantation.
5. 5. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
6. 6. Active human immunodeficiency virus (HIV), active hepatitis B or C. A positive HIV or viral hepatitis test result should be discussed between the Investigator and Sponsor prior to enrollment.
7. 7. [CCI]
8. 8. 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.
9. 9. 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.
10. 10. Prior exposure to bitopertin.
11. 11. Concurrent or planned treatment with afamelanotide or dersimelagon during the study period.
12. 12. 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.
13. 13. New treatment for anemia, including initiation of iron supplementation, within 1 month of screening.
14. 14. 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 [CCI} days prior to the first dose and throughout the study.
15. 15. Current or planned treatment with antipsychotic medication.
16. 16. Hemoglobin <10 g/dL at screening.
17. 17. Participation in other interventional clinical studies within 30 days prior to screening.
18. 18. If female, pregnant, planning to become pregnant, or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 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
2. Percent change from baseline in whole-blood metal-free PPIX levels at 6 months
3. Safety and tolerability, as assessed by adverse events (AEs) and laboratory results, over the 6-month treatment period

Secondary endpoints 3

1. Occurrence of phototoxic reactions over the 6-month treatment period
2. 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
3. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Disc Medicine Inc.

Sponsor organisation

Disc Medicine Inc.

Address

321 Arsenal Street Suite 101

City

Watertown

Postcode

02472-5710

Country

United States

Scientific contact point

Organisation

Disc Medicine Inc.

Contact name

Disc Medicine Clinical Trials

Public contact point

Organisation

Disc Medicine Inc.

Contact name

Disc Medicine Clinical Trials

Third parties 13

Locations

9 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 107 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications