The goal of this clinical trial is to learn if bitopertin works and is safe to treat EPP or XLP in participants 12 years or older. The main questions it aims to answer are:
* Whether bitopertin increases pain-free sunlight exposure after 6 months of treatment in participants with EPP or XLP.
* How PPIX concentration levels change from before bitopertin treatment to after 6 months of treatment.
Researchers will compare bitopertin to a placebo look-alike substance that contains no drug.
Participants will complete daily questionnaires and attend study visits for assessments.
Eligibility
Sex
ALL
Min age
12 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Aged 12 years or older at the time of study consent.
2. Diagnosis of EPP or XLP, based on medical history by ferrochelatase (FECH) or aminolevulinic acid synthase 2 (ALAS2) genotyping or by biochemical porphyrin analysis.
3. Minimum daily Sun Exposure Diary compliance ≥85% on Days -14 through Day -1, inclusive, during screening, and at least 1 successfully completed Sun Exposure Challenge (adults only, as this assessment is optional for adolescents) or historical recall of time to prodrome
4. Body weight ≥32 kg (ages 12 to \<18 years), body mass index ≥18.5 kg/m2 (ages ≥18 years) at screening.
5. Washout of at least 2 months prior to screening of afamelanotide and dersimelagon, if applicable.
6. Aspartate aminotransferase and alanine transaminase \<3× upper limit of normal (ULN)and total bilirubin \<2× ULN (unless documented Gilbert syndrome) at screening. Albumin \>lower limit of normal (LLN).
7. Willing to practice highly effective methods of birth control (both males who have partners of childbearing potential and females of childbearing potential during screening, while taking study drug, and for at least 30 days after the last dose of study drug).
Exclusion Criteria:
1. Major surgery within 8 weeks before screening or incomplete recovery from any previous surgery.
2. Other than EPP or XLP, an inherited intrinsic or extrinsic red cell disease associated with anemia.
3. Known hypersensitivity to any component of the study drug.
4. History of liver transplantation or anticipated need for liver transplantation.
5. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
6. Active human immunodeficiency virus (HIV), active hepatitis B or C.
7. 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.
8. 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:
9. Prior exposure to bitopertin.
10. Concurrent or planned treatment with afamelanotide or dersimelagon during the study period.
11. 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.
12. New treatment for anemia, including initiation of iron supplementation, within 1 month of screening.
13. Current or planned use of any drugs or herbal remedies known to be strong or moderate inhibitors or inducers of cytochrome P450 (CYP)3A4 enzymes for 28 days prior to the first dose and throughout the study.
14. Current or planned treatment with antipsychotic medication.
Laboratory Exclusions:
15. Hemoglobin \<10 g/dL at screening.
Miscellaneous:
16. Participation in other interventional clinical studies within 30 days prior to screening.
17. If female, pregnant or breastfeeding.
Primary outcome measure(s)
Average monthly total time in sunlight on days without pain from a phototoxic reaction between 10:00 to 18:00 (10:00 AM to 6:00 PM) after 6 months (24 weeks) of treatment — 24 weeks
Percent change from baseline in whole-blood metal-free PPIX levels at 6 months — 24 weeks
Safety and tolerability, as assessed by adverse events (AEs) and laboratory results, over the 6-month treatment period — 24 weeks
Trial sites (27)
Facility
City
Region
Status
Marvel Clinical Research
Huntington Beach
California
University of California San Francisco
San Francisco
California
University of Miami Miller School of Medicine
Miami
Florida
Massachusetts General Hospital
Boston
Massachusetts
MetroBoston Clinical Partners
Boston
Massachusetts
Henry Ford Health System
Detroit
Michigan
Mount Sinai Hospital
New York
New York
Wake Forest University
Winston-Salem
North Carolina
Remington-Davis Clinical Research
Columbus
Ohio
University of Texas Medical Branch
Galveston
Texas
University of Washington
Seattle
Washington
Royal Prince Alfred Hospital
Camperdown
New South Wales
The Royal Melbourne Hospital
Parkville
Victoria
UZ Leuven
Leuven
Belgium
University of Alberta
Edmonton
Alberta
CHU de Nantes - Hôtel Dieu, Service de dermatologie
Nantes
France
Centre d'Investigation Clinique (CIC) Hôpital Bichat - Claude-Bernard
Paris
France
Charité - Universitätsmedizin Berlin, Institute of Allergology
Berlin
Germany
Klinikum Chemnitz gGmbH
Chemnitz
Saxony
Children's Health Ireland (CHI)
Dublin
Ireland
Instituto Dermatologico San Gallicano Istituti Fisioterapici Ospitalieri IRCCS
Roma
Italy
Erasmus MC
Rotterdam
The Netherlands
Hospital Clinic de Barcelona
Barcelona
Spain
Karolinska University Hospital
Stockholm
Sweden
Guy's and St Thomas' NHS Foundation Trust
London
England
Clinical Research Centre, Ninewells Hospital & Medical School , NHS Tayside
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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