Clinical trial NCT05308472: Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants with EPP
Official title: (AURORA) a Randomized, Double-blind, Placebo-Controlled Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and Protoporphyrin IX (PPIX) Concentrations in Participants with Erythropoietic Protoporphyria (EPP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Erythropoietic Protoporphyria
Keywords: EPP
DISC-1459
RO4917838
porphyria
Lead sponsor: Disc Medicine, Inc
Sponsor class: INDUSTRY
First posted: 2022-04-04
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, multi-center, double-blind, placebo-controlled, parallel group study of bitopertin to evaluate the safety, tolerability, efficacy, and PPIX concentration change in participants with EPP. Participants may roll over to an open label extension portion after completing the double-blind treatment period.


Eligibility criteria: Inclusion Criteria:

1. Aged 18 years or older at the time of signing the informed consent form (ICF).
2. Diagnosis of EPP, based on medical history by ferrochelatase ( FECH) genotyping or by biochemical porphyrin analysis.
3. Body weight ≥50 kg.
4. Washout of at least 2 months prior to Screening of afamelanotide and dersimelagon, if applicable.
5. Aspartate aminotransferase (AST) and alanine transaminase (ALT) \<2× upper limit of normal (ULN) and total bilirubin \<ULN (unless documented Gilbert syndrome) at Screening. Albumin \>lower limit of normal (LLN).

Exclusion Criteria:

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), 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. 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.

Primary outcomes:
measure: Percent change from baseline in whole blood metal-free PPIX levels
timeFrame: 121 days
Secondary outcomes:
measure: Total hours of sunlight exposure to skin on days with no pain from 1000 to 1800 hours (10:00am to 6:00pm)
timeFrame: 121 days
measure: Daily sunlight exposure time (minutes) to first prodromal symptom (burning, tingling, itching, or stinging) associated with sunlight exposure between 1 hour post-sunrise and 1 hour pre-sunset
timeFrame: 121 days
measure: Pain intensity of phototoxic reactions according to a Likert scale (0-10)
timeFrame: 121 days
measure: Incidence of treatment-emergent adverse events
timeFrame: 121 days
measure: Erythrocyte total PPIX concentrations
timeFrame: 121 days
measure: Plasma total PPIX concentrations
timeFrame: 121 days
measure: Whole blood total PPIX concentrations
timeFrame: 121 days
measure: Plasma bitopertin concentrations
timeFrame: 121 days
Other outcomes:
measure: Plasma maximum measured drug concentration (Cmax)
timeFrame: 121 days
measure: Time of maximum concentration (Tmax)
timeFrame: 121 days
measure: Area under the concentration-time curve (AUC)
timeFrame: 121 days
Locations:
city: Birmingham
country: United States
facility: University of Alabama Hospital
state: Alabama
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
city: Philadelphia
country: United States
facility: Einstein Medical Center
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Disc Medicine
name: Will Savage, MD PhD
role: STUDY_DIRECTOR
References: