Erythropoietic ProtoporphyriaPhase 2NCT05308472
Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants With EPP
A Phase 2 study testing DISC-1459 in people with Erythropoietic Protoporphyria, run by Disc Medicine, Inc at 9 sites in United States.
Trial summary
This is a Phase 2, multi-center, double-blind, placebo-controlled, parallel group study of bitopertin to evaluate the safety, tolerability, efficacy, and PPIX concentration change in participants with EPP. Participants may roll over to an open label extension portion after completing the double-blind treatment period. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Erythropoietic Protoporphyria
- 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
- 75 participants
- Where
- 9 sitesUnited States
- Study dates
- 31 Oct 2022to 23 Aug 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 years or older at the time of signing the informed consent form (ICF).
- Diagnosis of EPP, based on medical history by ferrochelatase ( FECH) genotyping or by biochemical porphyrin analysis.
- Body weight ≥50 kg.
- Washout of at least 2 months prior to Screening of afamelanotide and dersimelagon, if applicable.
- Aspartate aminotransferase (AST) and alanine transaminase (ALT) <2× upper limit of normal (ULN) and total bilirubin <ULN (unless documented Gilbert syndrome) at Screening. Albumin >lower limit of normal (LLN).
Who cannot join
- Medical History:
- Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
- Other than EPP, an inherited or acquired red cell disease associated with anemia.
- A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug.
- History of liver transplantation.
- History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
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- 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:
- 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, in the 2 months prior to Screening.
- Current or planned use of any drugs or herbal remedies known to be strong inhibitors or inducers of CYP3A4 enzymes for 28 days prior to the first dose and throughout the study.
- Laboratory Exclusions:
- Hemoglobin <10 g/dL at Screening.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Alabama Hospital
Birmingham, Alabama, 35233
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Texas
Galveston, Texas, 77550
University of Miami Miller School of Medicine
Miami, Florida, 33136
Mount Sinai Hospital
New York, New York, 10029
Einstein Medical Center
Philadelphia, Pennsylvania, 19141
University of California San Francisco
San Francisco, California, 94117
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157
About this study
Official title: (AURORA) A Randomized, Double-blind, Placebo-Controlled Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and Protoporphyrin IX (PPIX) Concentrations in Participants With Erythropoietic Protoporphyria (EPP)
This is a Phase 2, multi-center, double-blind, placebo-controlled, parallel group study of bitopertin to evaluate the safety, tolerability, efficacy, and PPIX concentration change in participants with EPP. Participants may roll over to an open label extension portion after completing the double-blind treatment period.
- Conditions
- Erythropoietic Protoporphyria
- Being tested
- DISC-1459, Placebo
- Keywords
- EPP, DISC-1459, RO4917838, porphyria
- Medical subject headings
- Protoporphyria, Erythropoietic, Porphyrias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DISC-1459Drug
Also called Bitopertin, RO4917838
Oral dose level 1, once a day for 120 days
DISC-1459Drug
Also called Bitopertin, RO4917838
Oral dose level 2, once a day for 120 days
PlaceboDrug
Oral dose, once a day for 120 days
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| DISC-1459 oral dose level 1 | Experimental | Not described Receives: Drug: DISC-1459 |
| DISC-1459 oral dose level 2 | Experimental | Not described Receives: Drug: DISC-1459 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Whole Blood Metal-free PPIX Levels
Percent change from baseline in PPIX concentration was analyzed using a mixed model repeated measures analysis in the ITT population.
Measured: 121 days
Secondary outcomes (8)
Total Hours of Sunlight Exposure to Skin on Days With no Pain From 1000 to 1800 Hours (10:00am to 6:00pm)
Cumulative total hours of sunlight exposure on days with no pain from 1000 to 1800 hours from baseline to Day 121 (EOS) was analyzed using analysis of variance in the ITT population.
Measured: 121 days
Daily Sunlight Exposure Time (Minutes) to First Prodromal Symptom (Burning, Tingling, Itching, or Stinging) Associated With Sunlight Exposure Between 1 Hour Post-sunrise and 1 Hour Pre-sunset
Participants exposed their skin to sunlight once a week and measured the time it takes to experience a prodrome. The time (minutes) to first prodromal symptom (e.g., burning, tingling, itching, or stinging) associated with sunlight exposure was recorded in a diary. This sun exposure challenge was performed weekly. The average time (minutes) to first prodromal symptom (e.g., burning, tingling, itching, or stinging) associated with sunlight exposure was averaged over two-week intervals through Study Day 121.
Measured: 121 days
Total Pain Intensity
The maximum total daily pain intensity scores of phototoxic reactions over the entire treatment period (D1-D121). The maximum pain score of a phototoxic reaction was measured on a Likert Scale (0-10). Total scores range from 0-1210. A score of "0" is the best outcome; and higher scores are a worse outcome. The maximum pain values on a scale of 0-10 in a day were summed across 121 days.
Measured: Sum of Day 1 to Day 121
Incidence of Treatment-emergent Adverse Events
Incidence of treatment-emergent adverse events
Measured: 121 days
Erythrocyte Total PPIX Concentrations
Percent change from baseline in erythrocyte total PPIX concentration was summarized by analysis visit in the ITT population.
Measured: 121 days
Plasma Total PPIX Concentrations
Percent change from baseline in plasma total PPIX concentration was summarized by analysis visit in the ITT population.
Measured: 121 days
Whole Blood Total PPIX Concentrations
Percent change from baseline in whole blood total PPIX concentration was summarized by analysis visit in the ITT population.
Measured: 121 days
Plasma Bitopertin Concentrations
Day 29 plasma bitopertin concentrations, 4 hours post-dose
Measured: Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2022
- Study start31 Oct 2022
- Primary completion20 Feb 2024
- Study completion23 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Erythropoietic ProtoporphyriaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 75 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
- NCT05308472
- Sponsor's protocol ID
- DISC-1459-201
- Status last verified
- Dec 2025
- First submitted
- 21 Mar 2022
- Last updated
- 8 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (AURORA) A Randomized, Double-blind, Placebo-Controlled Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and Protoporphyrin IX (PPIX) Concentrations in Participants With Erythropoietic Protoporphyria (EPP)
- ClinicalTrials.gov ID
- NCT05308472
- Acronym / sponsor ID
- DISC-1459-201
- Conditions
- Erythropoietic Protoporphyria
- Keywords
- EPP, DISC-1459, RO4917838, porphyria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Disc Medicine, IncIndustry (pharma, biotech, devices)
- Study start
- 31 Oct 2022 (actual)
- Primary completion
- 20 Feb 2024 (actual)
- Study completion
- 23 Aug 2024 (actual)
- First posted
- 4 Apr 2022 (actual)
- Results
- Posted 8 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, multi-center, double-blind, placebo-controlled, parallel group study of bitopertin to evaluate the safety, tolerability, efficacy, and PPIX concentration change in participants with EPP. Participants may roll over to an open label extension portion after completing the double-blind treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| DISC-1459 oral dose level 1 | Experimental | Drug: DISC-1459 |
| DISC-1459 oral dose level 2 | Experimental | Drug: DISC-1459 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged 18 years or older at the time of signing the informed consent form (ICF).
- Diagnosis of EPP, based on medical history by ferrochelatase ( FECH) genotyping or by biochemical porphyrin analysis.
- Body weight ≥50 kg.
- Washout of at least 2 months prior to Screening of afamelanotide and dersimelagon, if applicable.
- Aspartate aminotransferase (AST) and alanine transaminase (ALT) <2× upper limit of normal (ULN) and total bilirubin <ULN (unless documented Gilbert syndrome) at Screening. Albumin >lower limit of normal (LLN).
Key exclusion criteria (16 listed)
- Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
- Other than EPP, an inherited or acquired red cell disease associated with anemia.
- A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug.
- History of 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 |
|---|---|---|
| DISC-1459Also: Bitopertin, RO4917838Oral dose level 1, once a day for 120 days | Drug | DISC-1459 oral dose level 1 |
| DISC-1459Also: Bitopertin, RO4917838Oral dose level 2, once a day for 120 days | Drug | DISC-1459 oral dose level 2 |
| PlaceboOral dose, once a day for 120 days | Drug | Placebo |
Primary outcome
Percent Change From Baseline in Whole Blood Metal-free PPIX Levels
Time frame: 121 days
Percent change from baseline in PPIX concentration was analyzed using a mixed model repeated measures analysis in the ITT population.
8 secondary outcomes
Total Hours of Sunlight Exposure to Skin on Days With no Pain From 1000 to 1800 Hours (10:00am to 6:00pm)
Time frame: 121 days
Daily Sunlight Exposure Time (Minutes) to First Prodromal Symptom (Burning, Tingling, Itching, or Stinging) Associated With Sunlight Exposure Between 1 Hour Post-sunrise and 1 Hour Pre-sunset
Time frame: 121 days
Total Pain Intensity
Time frame: Sum of Day 1 to Day 121
Incidence of Treatment-emergent Adverse Events
Time frame: 121 days
Erythrocyte Total PPIX Concentrations
Time frame: 121 days
Plasma Total PPIX Concentrations
Time frame: 121 days
Whole Blood Total PPIX Concentrations
Time frame: 121 days
Plasma Bitopertin Concentrations
Time frame: Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Erythropoietic Protoporphyria
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HELIOS: Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP or XLP
Erythropoietic Protoporphyria
RecruitingPhase 2/3
A Study to Investigate PORT-77 Oral Dosing Compared With Placebo in Participants With Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP)
Erythropoietic Protoporphyria (EPP), X-Linked Protoporphyria (XLP)
Active, not recruitingPhase 3
Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)
EPP, XLP
RecruitingObservational study
Longitudinal Study of the Porphyrias
Acute Porphyrias, Cutaneous Porphyrias
RecruitingObservational study
Observational Study of Adults and Adolescents With Erythropoietic Protoporphyria (EPP) and X-linked Porphyria (XLP)
Erythropoietic Protoporphyria (EPP), X-Linked Porphyria (XLP)
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
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DISC-1459 in people with Erythropoietic Protoporphyria, run by Disc Medicine, Inc at 9 sites in United States.
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 5 inclusion and 16 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 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent Change From Baseline in Whole Blood Metal-free PPIX Levels (time frame: 121 days). 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 8 Jan 2026.