Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants With EPP

Erythropoietic Protoporphyria Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05308472
• Other study ID #: DISC-1459-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 31, 2022
• Est. completion date: June 2024

Study information

• Verified date: April 2024
• Source: Disc Medicine, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: June 2024
• Est. primary completion date: February 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Erythropoietic Protoporphyria

Intervention

Drug:
• DISC-1459
Oral dose level 1, once a day for 120 days
• DISC-1459
Oral dose level 2, once a day for 120 days
• Placebo
Oral dose, once a day for 120 days
• DISC-1459
Oral dose level 1, once a day for up to 8 months

Locations

Country	Name	City	State
United States	University of Alabama Hospital	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Texas	Galveston	Texas
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Mount Sinai Hospital	New York	New York
United States	Einstein Medical Center	Philadelphia	Pennsylvania
United States	University of California San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Atrium Health Wake Forest Baptist	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Disc Medicine, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma maximum measured drug concentration (Cmax)		121 days
Other	Time of maximum concentration (Tmax)		121 days
Other	Area under the concentration-time curve (AUC)		121 days
Primary	Percent change from baseline in whole blood metal-free PPIX levels		121 days
Secondary	Total hours of sunlight exposure to skin on days with no pain from 1000 to 1800 hours (10:00am to 6:00pm)		121 days
Secondary	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		121 days
Secondary	Pain intensity of phototoxic reactions according to a Likert scale (0-10)		121 days
Secondary	Incidence of treatment-emergent adverse events		121 days
Secondary	Erythrocyte total PPIX concentrations		121 days
Secondary	Plasma total PPIX concentrations		121 days
Secondary	Whole blood total PPIX concentrations		121 days
Secondary	Plasma bitopertin concentrations		121 days