Erythropoietic Protoporphyria (EPP)Phase 3APOLLONCT06910358
Study of Bitopertin in Participants With EPP or XLP (APOLLO)
A Phase 3 study testing DISC-1459 in people with Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP), run by Disc Medicine, Inc at 27 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Erythropoietic Protoporphyria (EPP), X-Linked Protoporphyria (XLP)
- What is being tested?
- DISC-1459
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 183 participants
- Where
- 27 sitesin 12 countries
- Study dates
- 4 Apr 2025to 8 Sep 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
- Laboratory Exclusions:
- Hemoglobin <10 g/dL at screening.
- Miscellaneous:
- Participation in other interventional clinical studies within 30 days prior to screening.
- If female, pregnant or breastfeeding.
Trial locations and contacts
27 sites in 12 countries.
27 sites in 12 countries
United States11 sites
Massachusetts General Hospital
Boston, Massachusetts, 02115
MetroBoston Clinical Partners
Boston, Massachusetts, 02135
Remington-Davis Clinical Research
Columbus, Ohio, 43215
Henry Ford Health System
Detroit, Michigan, 48202
University of Texas Medical Branch
Galveston, Texas, 77550
Marvel Clinical Research
Huntington Beach, California, 92647
University of Miami Miller School of Medicine
Miami, Florida, 33146
Mount Sinai Hospital
New York, New York, 10029
University of California San Francisco
San Francisco, California, 94143
University of Washington
Seattle, Washington, 98195
Wake Forest University
Winston-Salem, North Carolina, 27157
United Kingdom3 sites
Clinical Research Centre, Ninewells Hospital & Medical School , NHS Tayside
Dundee, Scotland, DD1 9SY
Guy's and St Thomas' NHS Foundation Trust
London, England, SE1 9RT
Photobiology Unit, Salford Royal Hospital
Salford, M6 8HD
Australia2 sites
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
The Royal Melbourne Hospital
Parkville, Victoria, 3050
France2 sites
CHU de Nantes - Hôtel Dieu, Service de dermatologie
Nantes, France, 44093
Centre d'Investigation Clinique (CIC) Hôpital Bichat - Claude-Bernard
Paris, France, 75018
Germany2 sites
Charité - Universitätsmedizin Berlin, Institute of Allergology
Berlin, Germany, 12203
Klinikum Chemnitz gGmbH
Chemnitz, Saxony, 09116
Italy1 site
Instituto Dermatologico San Gallicano Istituti Fisioterapici Ospitalieri IRCCS
Roma, 53-00144
About this study
Official title: 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.
- Being tested
- Placebo, DISC-1459
- Keywords
- EPP, XLP, DISC-1459, RO4917838, porphyria
- Medical subject headings
- Protoporphyria, Erythropoietic, Protoporphyria, Erythropoietic, X-Linked Dominant, Porphyrias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Oral dose, once a day for 24 weeks
DISC-1459Drug
Also called Bitopertin, RO4917838
Oral dose, once a day for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| DISC-1459 oral dose | Experimental | Not described Receives: Drug: DISC-1459 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 weeks
Percent change from baseline in whole-blood metal-free PPIX levels at 6 months
Measured: 24 weeks
Safety and tolerability, as assessed by adverse events (AEs) and laboratory results, over the 6-month treatment period
Measured: 24 weeks
Secondary outcomes (3)
Occurrence of phototoxic reactions over the 6-month treatment period
Measured: 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
Measured: 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
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2025
- Study start4 Apr 2025
- Primary completion8 Sep 2026
- Study completion8 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Erythropoietic Protoporphyria (EPP)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- Disc Medicine, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Will Savage, MD, PhD, Study director, Disc Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06910358
- Sponsor's protocol ID
- DISC-1459-301
- Other IDs
- 2024-520407-27-00
- Acronym
- APOLLO
- Status last verified
- Oct 2026
- First submitted
- 17 Mar 2025
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06910358
- Acronym / sponsor ID
- APOLLO / DISC-1459-301
- Keywords
- EPP, XLP, DISC-1459, RO4917838, porphyria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- Disc Medicine, IncIndustry (pharma, biotech, devices)
- Study start
- 4 Apr 2025 (actual)
- Primary completion
- 8 Sep 2026 (actual)
- Study completion
- 8 Sep 2026 (actual)
- First posted
- 4 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| DISC-1459 oral dose | Experimental | Drug: DISC-1459 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboOral dose, once a day for 24 weeks | Drug | Placebo |
| DISC-1459Also: Bitopertin, RO4917838Oral dose, once a day for 24 weeks | Drug | DISC-1459 oral dose |
Primary outcome
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
Time frame: 24 weeks
Percent change from baseline in whole-blood metal-free PPIX levels at 6 months
Time frame: 24 weeks
Safety and tolerability, as assessed by adverse events (AEs) and laboratory results, over the 6-month treatment period
Time frame: 24 weeks
3 secondary outcomes
Occurrence of phototoxic reactions over the 6-month treatment period
Time frame: 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
Time frame: 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
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Erythropoietic Protoporphyria (EPP)
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RecruitingObservational study
Longitudinal Study of the Porphyrias
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Will Savage, MD, PhD study director
Disc Medicine
27 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing DISC-1459 in people with Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP), run by Disc Medicine, Inc at 27 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, United Kingdom, Australia, France, Germany and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 24 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.