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

NCT07123363 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: IRB00118441
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Protoporphyria

Keywords

Erythropoietic Protoporphyria; X-linked Protoporphyria; Bitopertin

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 104

Secondary Outcomes (5)

• Percent Change in Protoporphyrin IX (PP) Serum Levels

  baseline to month 12, month 12 to month 24

• Number of Participants with Change in Histopathology

  baseline to month 24

• Percent Change in Protoporphyrin IX (PP) Bile Levels

  baseline to month 24

• Percent Change in Protoporphyrin IX (PP) Liver Levels

  baseline to month 12, baseline to month 24

• Percent Change in Protoporphyrin IX (PP) Stool Levels

  baseline to month 24

Other Outcomes (4)

• Patient Global Impression of Severity

  baseline, week 26, week 52, week 78, week 104

• Patient Global Impression of Change

  baseline, week 26, week 52, week 78, week 104

• Patient-Reported Outcomes Measurement Information System - Social Isolation

  baseline, week 26, week 52, week 78, week 104

Study Arms (1)

bitopertin

EXPERIMENTAL

bitopertin 60 mg per day

Drug: bitopertin

Interventions

bitopertin DRUG

bitopertin 60 mg will be taken once daily by mouth

Also known as: DISC-1459

bitopertin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

MeSH Terms

Conditions

Protoporphyria, Erythropoietic; Protoporphyria, Erythropoietic, X-Linked Dominant

Interventions

(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Porphyrias; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Herbert Bonkovsky, MD

  Atrium Health Wake Forest Baptist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2025
• First Posted: August 14, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2035
• Study Completion (Estimated): December 1, 2035
• Last Updated: January 29, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share