ProtoporphyriaPhase 1NCT07123363
Effect of Bitopertin on the Liver and on Levels of Protoporphyrin IX in Bile, Blood, Liver, and Stool in Patients With Erythropoietic Protoporphyria/X-linked Protoporphyria and Increased Liver Stiffness and/or Liver Enzymes at Baseline
A Phase 1 study testing bitopertin in people with Protoporphyria, run by Wake Forest University Health Sciences.
Trial summary
The primary goal of this study is to assess safety and tolerability of bitopertin in subjects with Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP) and evidence of compensated liver disease. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Protoporphyria
- What is being tested?
- bitopertin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2026to Dec 2035
- Phase
- Phase 1
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of EEP or XLP that has been biochemically and genetically verified prior diagnosis of EPP or XLP
- Age 18-75 years
- Increased liver stiffness at baseline, defined as stiffness measurement [E value] by: Fibroscan >7 kPa; MRE that is >3.0 kPa; Velacur/Sonicincyte that is >6.0 kPa; and/or elevated liver enzymes: serum ALT > 2 X upper limit of normal (ULN), but not greater than 5 X ULN and/or serum AP > 2 X ULN, but not greater than 5 X ULN
- INR < 1.4
- Compensated liver disease at baseline, defined as lack of clinically evident ascites, encephalopathy, hepatocellular carcinoma, clinically evident icterus or jaundice, peripheral edema.
- Willingness and ability to volunteer and provide informed consent for a long-term study that will include liver biopsies and collection of bile from the second portion of the duodenum, at baseline and at the end of study. In addition, follow-up visits will be planned every 26 weeks throughout the study, with plans for repeat routine/safety labs at each visit and for measures of liver stiffness and markers of hepatic status and fibrosis (Fib-4, APRI, ELF, Fibrotest) performed once every 6 months.
Who cannot join
- Chronic hepatitis B, C, D, or E;
- Human immunodeficiency (HIV) infection;
- Alcohol use > 14 units/week for men or > 7 units/week for women;
- Pregnancy or breast feeding among women;
- Any known active malignancy other than small and localized squamous or basal cell carcinoma of the skin;
- Advanced or decompensated heart, lung, kidney, liver, or neuro-psychiatric disease;
Show all 9Show fewer
- History of diagnosed depression or suicidality;
- History of diagnosed substance abuse or poor impulse control;
- Any other conditions that, in the opinion of the Investigator, renders the individual unfit to participate
About this study
The primary goal of this study is to assess safety and tolerability of bitopertin in subjects with Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP) and evidence of compensated liver disease.
Read the detailed description
This in an open-label, investigator-initiated study of bitopertin (60 mg/day) in selected and carefully monitored participants with Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP) who have increased liver stiffness and/or elevated liver enzymes at baseline.This study is designed to evaluate whether bitopertin is effective in reducing hepatic and biliary levels of protoporphyrin IX (PP), which over time, with chronic and ongoing bitopertin treatment, will ameliorate and forestall progression of PP hepatopathy, providing an additional major benefit and reason for its chronic use in patients with EPP/XLP.
- Conditions
- Protoporphyria
- Being tested
- bitopertin
- Keywords
- Erythropoietic Protoporphyria, X-linked Protoporphyria, Bitopertin
- Medical subject headings
- Protoporphyria, Erythropoietic, Protoporphyria, Erythropoietic, X-Linked Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bitopertinDrug
Also called DISC-1459
bitopertin 60 mg will be taken once daily by mouth
| Study group | Role | What they receive |
|---|---|---|
| bitopertin | Experimental | bitopertin 60 mg per day Receives: Drug: bitopertin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of treatment emergent adverse events (TEAE)
Number of treatment emergent adverse events (TEAE). Adverse events that begin after the first administration of study drug, or existing adverse events that worsen after the first dose of study drug will be considered TEAEs.
Measured: Week 104
Secondary outcomes (5)
Percent Change in Protoporphyrin IX (PP) Serum Levels
To assess effects of bitopertin on levels of protoporphyrin IX (PP) and other porphyrins in the whole blood, plasma, and red blood cells
Measured: baseline to month 12, month 12 to month 24
Number of Participants with Change in Histopathology
To assess effects of bitopertin on hepatic histopathology the number of participants with change in histopathologic evidence will be tracked. Histopathology consists of histopathologic evidence of hepatic fibrosis, necroinflammation, fat, cholestasis, bile plugs, birefringent brown deposits in the liver, or other histopathology, as estimated by an experienced hepato-pathologist.
Measured: baseline to month 24
Percent Change in Protoporphyrin IX (PP) Bile Levels
the percent change of Protoporphyrin IX (PP) in bile will be used to assess effects of bitopertin on PP levels
Measured: baseline to month 24
Percent Change in Protoporphyrin IX (PP) Liver Levels
the percent change in Protoporphyrin IX (PP) in the liver will be measured by change in liver stiffness measured by vibration controlled elastography with use of dedicated instruments designed for this purpose (Fibroscan, Velocur)
Measured: baseline to month 12, baseline to month 24
Percent Change in Protoporphyrin IX (PP) Stool Levels
the percent change in Protoporphyrin IX (PP) in stool will be used to assess effects of bitopertin on PP levels
Measured: baseline to month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2025
- Study startJan 2026 (estimated)
- Primary completionDec 2035 (estimated)
- Study completionDec 2035 (estimated)
Why it stopped: department leadership decided not to proceed with study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ProtoporphyriaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Herbert Bonkovsky, MD, Principal investigator, Atrium Health Wake Forest Baptist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07123363
- Sponsor's protocol ID
- IRB00118441
- Status last verified
- Aug 2025
- First submitted
- 7 Aug 2025
- Last updated
- 29 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Bitopertin on the Liver and on Levels of Protoporphyrin IX in Bile, Blood, Liver, and Stool in Patients With Erythropoietic Protoporphyria/X-linked Protoporphyria and Increased Liver Stiffness and/or Liver Enzymes at Baseline
- ClinicalTrials.gov ID
- NCT07123363
- Acronym / sponsor ID
- IRB00118441
- Conditions
- Protoporphyria
- Keywords
- Erythropoietic Protoporphyria, X-linked Protoporphyria, Bitopertin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: department leadership decided not to proceed with study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Jan 2026 (estimated)
- Primary completion
- Dec 2035 (estimated)
- Study completion
- Dec 2035 (estimated)
- First posted
- 14 Aug 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 primary goal of this study is to assess safety and tolerability of bitopertin in subjects with Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP) and evidence of compensated liver disease.
Detailed description
This in an open-label, investigator-initiated study of bitopertin (60 mg/day) in selected and carefully monitored participants with Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP) who have increased liver stiffness and/or elevated liver enzymes at baseline.This study is designed to evaluate whether bitopertin is effective in reducing hepatic and biliary levels of protoporphyrin IX (PP), which over time, with chronic and ongoing bitopertin treatment, will ameliorate and forestall progression of PP hepatopathy, providing an additional major benefit and reason for its chronic use in patients with EPP/XLP.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bitopertin | Experimental | Drug: bitopertinbitopertin 60 mg per day |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of EEP or XLP that has been biochemically and genetically verified prior diagnosis of EPP or XLP
- Age 18-75 years
- Increased liver stiffness at baseline, defined as stiffness measurement [E value] by: Fibroscan >7 kPa; MRE that is >3.0 kPa; Velacur/Sonicincyte that is >6.0 kPa; and/or elevated liver enzymes: serum ALT > 2 X upper limit of normal (ULN), but not greater than 5 X ULN and/or serum AP > 2 X ULN, but not greater than 5 X ULN
- INR < 1.4
- Compensated liver disease at baseline, defined as lack of clinically evident ascites, encephalopathy, hepatocellular carcinoma, clinically evident icterus or jaundice, peripheral edema.
Key exclusion criteria (9 listed)
- Chronic hepatitis B, C, D, or E;
- Human immunodeficiency (HIV) infection;
- Alcohol use > 14 units/week for men or > 7 units/week for women;
- Pregnancy or breast feeding among women;
- Any known active malignancy other than small and localized squamous or basal cell carcinoma of the skin;
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 |
|---|---|---|
| bitopertinAlso: DISC-1459bitopertin 60 mg will be taken once daily by mouth | Drug | bitopertin |
Primary outcome
Number of treatment emergent adverse events (TEAE)
Time frame: Week 104
Number of treatment emergent adverse events (TEAE). Adverse events that begin after the first administration of study drug, or existing adverse events that worsen after the first dose of study drug will be considered TEAEs.
5 secondary outcomes
Percent Change in Protoporphyrin IX (PP) Serum Levels
Time frame: baseline to month 12, month 12 to month 24
Number of Participants with Change in Histopathology
Time frame: baseline to month 24
Percent Change in Protoporphyrin IX (PP) Bile Levels
Time frame: baseline to month 24
Percent Change in Protoporphyrin IX (PP) Liver Levels
Time frame: baseline to month 12, baseline to month 24
Percent Change in Protoporphyrin IX (PP) Stool Levels
Time frame: baseline to month 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Individual participant dataSharing planned: No
Related trials for Protoporphyria
Enrolling by invitationPhase 2/3
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.
Herbert Bonkovsky, MD principal investigator
Atrium Health Wake Forest Baptist
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bitopertin in people with Protoporphyria, run by Wake Forest University Health Sciences.
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 6 inclusion and 9 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: withdrawn, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was withdrawn before enrolling participants, so there are no results.
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?
Number of treatment emergent adverse events (TEAE) (time frame: Week 104). 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 29 Jan 2026.