Clinical Trials Register

Summary
EudraCT Number:	2025-000481-28
Sponsor's Protocol Code Number:	DISC-1459-202
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2026-03-26
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2025-000481-28

A.3

Full title of the trial

A Phase 2, Randomized, Open Label Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and Protoporphyrin IX (PPIX) Concentrations in Participants with Erythropoietic Protoporphyria (EPP)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to evaluate if Bitopertin is safe, well tolerated, and effective in patients with Erythropoietic Protoporphyria (EPP) including analyzing its effect on Protoporphyrin IX (PPIX) concentrations

A.3.2

Name or abbreviated title of the trial where available

BEACON

A.4.1

Sponsor's protocol code number

DISC-1459-202

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/352/2024

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Disc Medicine, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Disc Medicine, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Disc Medicine, Inc.
B.5.2	Functional name of contact point	Disc Medicine Clinical Trials
B.5.3	Address:
B.5.3.1	Street Address	321 Arsenal Street, Suite 101
B.5.3.2	Town/ city	Watertown, MA
B.5.3.3	Post code	02472
B.5.3.4	Country	United States
B.5.4	Telephone number	+1617-674-9274
B.5.6	E-mail	clinicaltrials@discmedicine.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/23/2761
D.3 Description of the IMP
D.3.1	Product name	Bitopertin 10 mg
D.3.2	Product code	DISC-1459
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Bitopertin
D.3.9.1	CAS number	845614-11-1
D.3.9.2	Current sponsor code	DISC-1459
D.3.9.4	EV Substance Code	SUB189342
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/23/2761
D.3 Description of the IMP
D.3.1	Product name	Bitopertin 30 mg
D.3.2	Product code	DISC-1459
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Bitopertin
D.3.9.1	CAS number	845614-11-1
D.3.9.2	Current sponsor code	DISC-1459
D.3.9.4	EV Substance Code	SUB189342
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Erythropoietic protoporphyria (EPP), and specifically the Protoporphyrin IX (PPIX) concentration in patients with EPP

E.1.1.1

Medical condition in easily understood language

A systemic disease called Erythropoietic protoporphyria (EPP), and specifically the concentration of an organic compound called Protoporphyrin IX (PPIX) in patients with this disease

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	24.0
E.1.2	Level	LLT
E.1.2	Classification code	10015289
E.1.2	Term	Erythropoietic protoporphyria
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To assess changes in protoporphyrin IX (PPIX) concentration in response to bitopertin treatment

E.2.2

Secondary objectives of the trial

• 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)

E.2.3

Trial contains a sub-study

E.3

Principal 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 <18 years of age and BMI ≥18.5 kg/m2 for adult participants.
4. Washout of at least 2 months prior to Screening of afamelanotide or dersimelagon, if applicable.
5. Aspartate aminotransferase (AST) and alanine transaminase (ALT) <2x upper limit of normal (ULN) and total bilirubin <ULN (unless documented Gilbert syndrome) at Screening. Albumin >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.

E.4

Principal 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.

E.5 End points

E.5.1

Primary end point(s)

• Percent change from baseline in whole blood metal-free PPIX levels

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 169

E.5.2

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)

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary endpoints: Day 169
Pharmacokinetic endpoints: Day 1, Day 2, and Day 29

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability of medicinal product

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Two different doses of the medicinal product are compared

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Australia

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Possible continuation of treatment for participants after End of Study visit for an additional 6 months; after the extension part within DISC-1459-202 study, participants can consent to roll into the separate DISC-1459-501 extension study.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Dermatology Research, The Royal Melbourne Hospital
G.4.3.4	Network Country	Australia
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	Royal Prince Alfred Hospital, Sydney
G.4.3.4	Network Country	Australia

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Australia

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