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

NCT ID: NCT07123363

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2035-12-31

Brief 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

bitopertin

bitopertin 60 mg per day

Group Type: EXPERIMENTAL

bitopertin

Intervention Type: DRUG

bitopertin 60 mg will be taken once daily by mouth

Interventions

bitopertin

bitopertin 60 mg will be taken once daily by mouth

Intervention Type: DRUG

Other Intervention Names

DISC-1459

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Herbert Bonkovsky, MD

Role: PRINCIPAL_INVESTIGATOR

Atrium Health Wake Forest Baptist

Central Contacts

Herbert Bonkovsky, MD

Role: CONTACT

Herbert.bonkovsky@advocatehealth.org

336-713-7341

Dee Faust

Role: CONTACT

denise.faust@advocatehealth.org

336-713-1442

Other Identifiers

IRB00118441

Identifier Type: -

Identifier Source: org_study_id