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

January 26, 2026 updated by: Wake Forest University Health Sciences
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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;
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: bitopertin
bitopertin 60 mg per day
Drug: bitopertin
bitopertin 60 mg will be taken once daily by mouth
Other Names:
  • DISC-1459

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Week 104

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent Change in Protoporphyrin IX (PP) Serum Levels
Time Frame: baseline to month 12, month 12 to month 24
To assess effects of bitopertin on levels of protoporphyrin IX (PP) and other porphyrins in the whole blood, plasma, and red blood cells
baseline to month 12, month 12 to month 24
Number of Participants with Change in Histopathology
Time Frame: baseline to month 24
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.
baseline to month 24
Percent Change in Protoporphyrin IX (PP) Bile Levels
Time Frame: baseline to month 24
the percent change of Protoporphyrin IX (PP) in bile will be used to assess effects of bitopertin on PP levels
baseline to month 24
Percent Change in Protoporphyrin IX (PP) Liver Levels
Time Frame: baseline to month 12, baseline to month 24
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)
baseline to month 12, baseline to month 24
Percent Change in Protoporphyrin IX (PP) Stool Levels
Time Frame: baseline to month 24
the percent change in Protoporphyrin IX (PP) in stool will be used to assess effects of bitopertin on PP levels
baseline to month 24

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Patient Global Impression of Severity
Time Frame: baseline, week 26, week 52, week 78, week 104
Three items with total score range 3-15. Higher score indicates higher level of erythropoietic protoporphyria severity
baseline, week 26, week 52, week 78, week 104
Patient Global Impression of Change
Time Frame: baseline, week 26, week 52, week 78, week 104
Five items with total score range 5-25. Higher score indicates erythropoietic protoporphyria have gotten worse since start of the study.
baseline, week 26, week 52, week 78, week 104
Patient-Reported Outcomes Measurement Information System - Social Isolation
Time Frame: baseline, week 26, week 52, week 78, week 104
Seven items with total score range 3-15. Higher score indicates poor quality of life.
baseline, week 26, week 52, week 78, week 104
Serum of Level of Bitopertin
Time Frame: baseline, week 26, week 52, week 78, week 104
Trough concentrations of bitopertin will measured by using HPLC-mass spectroscopic procedures
baseline, week 26, week 52, week 78, week 104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wake Forest University Health Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Herbert Bonkovsky, MD, Atrium Health Wake Forest Baptist

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2035

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2035

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 7, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 14, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00118441

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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