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: Completed
• Conditions: Erythropoietic Protoporphyria
• Intervention / Treatment: Drug: Placebo; Drug: DISC-1459; Drug: DISC-1459

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

Contacts and Locations

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

3

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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Whole Blood Metal-free PPIX Levels	Percent change from baseline in PPIX concentration was analyzed using a mixed model repeated measures analysis in the ITT population.	121 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Hours of Sunlight Exposure to Skin on Days With no Pain From 1000 to 1800 Hours (10:00am to 6:00pm)	Cumulative total hours of sunlight exposure on days with no pain from 1000 to 1800 hours from baseline to Day 121 (EOS) was analyzed using analysis of variance in the ITT population.	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	Participants exposed their skin to sunlight once a week and measured the time it takes to experience a prodrome. The time (minutes) to first prodromal symptom (e.g., burning, tingling, itching, or stinging) associated with sunlight exposure was recorded in a diary. This sun exposure challenge was performed weekly. The average time (minutes) to first prodromal symptom (e.g., burning, tingling, itching, or stinging) associated with sunlight exposure was averaged over two-week intervals through Study Day 121.	121 days
Total Pain Intensity	The maximum total daily pain intensity scores of phototoxic reactions over the entire treatment period (D1-D121). The maximum pain score of a phototoxic reaction was measured on a Likert Scale (0-10). Total scores range from 0-1210. A score of "0" is the best outcome; and higher scores are a worse outcome. The maximum pain values on a scale of 0-10 in a day were summed across 121 days.	Sum of Day 1 to Day 121
Incidence of Treatment-emergent Adverse Events	Incidence of treatment-emergent adverse events	121 days
Erythrocyte Total PPIX Concentrations	Percent change from baseline in erythrocyte total PPIX concentration was summarized by analysis visit in the ITT population.	121 days
Plasma Total PPIX Concentrations	Percent change from baseline in plasma total PPIX concentration was summarized by analysis visit in the ITT population.	121 days
Whole Blood Total PPIX Concentrations	Percent change from baseline in whole blood total PPIX concentration was summarized by analysis visit in the ITT population.	121 days
Plasma Bitopertin Concentrations	Day 29 plasma bitopertin concentrations, 4 hours post-dose	Day 29

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 (Actual): August 23, 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): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: EPP; porphyria; DISC-1459; RO4917838
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Skin Diseases; Skin Diseases, Genetic; Porphyrias, Hepatic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Protoporphyria, Erythropoietic; Porphyrias; (4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone
• 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
• product manufactured in and exported from the U.S.: No