Erythropoietic protoporphyria (EPP), and specifically the Protoporphyrin IX (PPIX) concentration in patients with EPP MedDRA version: 24.0 Level: LLT Classification code 10015289 Term: Erythropoietic protoporphyria System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Bitopertin 10 mg
Product Code: DISC-1459
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Bitopertin
CAS Number: 845614-11-1
Current Sponsor code: DISC-1459
Concentration uni
Sponsors
Disc Medicine, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants must meet all the following criteria to be eligible for enrollment in the study: 1. Aged 12 years and older upon study consent. 2. Diagnosis of EPP or X-linked protoporphyria (XLP), based on medical history of ferrochelatase (FECH) or ALAS2 genotyping or by biochemical porphyrin analysis. 3. Body weight =32 kg for participants lower limit of normal (LLN). 6. If male with female sexual partner(s) of childbearing potential, agrees he and partner will use one of the following acceptable methods of birth control during the study and for 30 days after the last study drug dose: a. abstinence b. stable hormonal contraceptive with a barrier method (e.g., condom [male or female] or diaphragm) c. intrauterine device, in place for at least 3 months d. surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation 7. If female of childbearing potential, defined as prior menarche, no hysterectomy, no bilateral oophorectomy, not postmenopausal (at least 12 months natural, spontaneous amenorrhea), must commit to one of the following methods of acceptable birth control during the study and for 30 days after the last study drug dose: a. abstinence b. stable hormonal contraceptive in conjunction with a barrier method (e.g., condom [male or female] or diaphragm) c. intrauterine device, in place for at least 3 months 8. Negative urine or serum pregnancy test (females of childbearing potential) at Screening (Days -28 to -1) AND Baseline (Day 1), prior to dosing. 9. Able to understand the study aims, procedures, and requirements, and provide written informed consent (and assent form if necessary). 10. Able to comply with all study procedures. Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 22 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participants meeting any of the following criteria are not eligible for study enrollment: Medical History: 1. Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery. 2. Other than EPP, an inherited or acquired red cell disease associated with anemia. 3. A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug. 4. History of liver transplantation. 5. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator. 6. Human immunodeficiency virus (HIV) with detectable viral load, or active hepatitis B or C. A positive hepatitis result, indicating active disease status, should be discussed between the Investigator and Sponsor prior to enrollment. 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. Concurrent or planned treatment with afamelanotide or dersimelagon during the study period. 10. 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. 11. New treatment for anemia, including initiation of iron supplementation, in the 2 months prior to Screening. 12. Current or planned use of any drugs or herbal remedies known to be strong inhibitors or inducers of CYP3A4 enzymes for 28 days prior to the first dose and throughout the study. Laboratory Exclusions: 13. Hemoglobin <10 g/dL at Screening. Miscellaneous: 14. If female, pregnant or breastfeeding. 15. Participation in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices within 30 days of Screening. 16. Grapefruit/Seville orange and food products containing these for 14 days prior to first dose and throughout the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess changes in protoporphyrin IX (PPIX) concentration in response to bitopertin treatment;Primary end point(s): • Percent change from baseline in whole blood metal-free PPIX levels;Timepoint(s) of evaluation of this end point: Day 169;Secondary Objective: • To characterize the effect of bitopertin on daily daylight tolerance • To assess the safety and tolerability of bitopertin at two dose levels • To characterize the relationship between bitopertin dose level and key biological indicators of mechanism engagement • To evaluate bitopertin pharmacokinetics (PK) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoint • Total hours of direct sunlight exposure to skin on days with no pain from 1000 to 1800 hours (10:00 AM to 6:00 PM) Secondary Endpoints • A two-week average daily sunlight exposure time (minutes) to first prodromal symptom (e.g., burning, tingling, itching, or stinging) associated with sunlight exposure between 1 hour post-sunrise and 1 hour pre-sunset. • Pain intensity of phototoxic reactions according to a Likert scale (0-10) • Safety and tolerability of bitopertin, as assessed by the incidence of treatment-emergent adverse events (TEAEs) • Erythrocyte metal-free PPIX concentrations • Plasma and whole blood total PPIX concentrations • Plasma bitopertin concentrations Pharmacokinetic Endpoints • Cmax • Observed time of the maximum drug concentration (Tmax) • AUC from time 0 to 24 hours post-dose on Day 1 (AUC0-24);Timepoint(s) of evaluation of this end point: Secondary endpoints: Day 169 Pharmacokinetic endpoints: Day 1, Day 2, and Day 29 | — |
Countries
Australia
Contacts
Public ContactDisc Medicine Clinical Trials
Disc Medicine, Inc.
Outcome results
None listed