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

(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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Erythropoietic Protoporphyria
• Intervention / Treatment: Drug: Placebo; Drug: DISC-1459; Drug: DISC-1459; Drug: DISC-1459

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Disc Medicine Clinical Trials; Phone Number: (617) 674 9274; Email: clinicaltrials@discmedicine.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Hospital
  • California
    • San Francisco, California, United States, 94117
      • University of California San Francisco
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Atrium Health Wake Forest Baptist
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center
  • Texas
    • Galveston, Texas, United States, 77550
      • University of Texas
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral dose, once a day for 120 days
Experimental: DISC-1459 oral dose level 1	Drug: DISC-1459; Oral dose level 1, once a day for 120 days; Other Names: Bitopertin; RO4917838; Drug: DISC-1459; Oral dose level 2, once a day for 120 days; Other Names: Bitopertin; RO4917838; Drug: DISC-1459; Oral dose level 1, once a day for up to 8 months; Other Names: Bitopertin; RO4917838
Experimental: DISC-1459 oral dose level 2	Drug: DISC-1459; Oral dose level 1, once a day for 120 days; Other Names: Bitopertin; RO4917838; Drug: DISC-1459; Oral dose level 2, once a day for 120 days; Other Names: Bitopertin; RO4917838; Drug: DISC-1459; Oral dose level 1, once a day for up to 8 months; Other Names: Bitopertin; RO4917838
Experimental: Open-Label Extension (optional)	Drug: DISC-1459; Oral dose level 1, once a day for 120 days; Other Names: Bitopertin; RO4917838; Drug: DISC-1459; Oral dose level 2, once a day for 120 days; Other Names: Bitopertin; RO4917838; Drug: DISC-1459; Oral dose level 1, once a day for up to 8 months; Other Names: Bitopertin; RO4917838

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in whole blood metal-free PPIX levels	121 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Total hours of sunlight exposure to skin on days with no pain from 1000 to 1800 hours (10:00am to 6:00pm)	121 days
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
Pain intensity of phototoxic reactions according to a Likert scale (0-10)	121 days
Incidence of treatment-emergent adverse events	121 days
Erythrocyte total PPIX concentrations	121 days
Plasma total PPIX concentrations	121 days
Whole blood total PPIX concentrations	121 days
Plasma bitopertin concentrations	121 days

Other Outcome Measures

Outcome Measure	Time Frame
Plasma maximum measured drug concentration (Cmax)	121 days
Time of maximum concentration (Tmax)	121 days
Area under the concentration-time curve (AUC)	121 days

Collaborators and Investigators

• Sponsor: Disc Medicine, Inc
• Investigators: Study Director: Will Savage, MD PhD, Disc Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2022
• Primary Completion (Actual): February 20, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: EPP; porphyria; DISC-1459; RO4917838
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Skin Diseases; Liver Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Porphyrias, Hepatic; Porphyrias; Protoporphyria, Erythropoietic
• Other Study ID Numbers: DISC-1459-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No