Study of the Selective GlyT1 Inhibitor Bitopertin for Steroid-Refractory Diamond-Blackfan Anemia

NCT05828108 | Completed Phase 1 FDA Drug

• 2 other identifiers: 10001528001528-H
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Diamond-Blackfan anemia (DBA) is an inherited disease that affects the bone marrow. People with DBA have chronic anemia that can be severe. Many must have frequent transfusions of red blood cells. Current treatments for DBA all have risks of serious side effects. Better treatments are needed. Objective: To test a new drug (bitopertin) in people with DBA. Eligibility: People aged 18 or older with DBA. Design: Participants will be screened. They will have a physical exam; they will have blood tests and a test of their heart function. They will have a bone marrow biopsy: An area of their hip will be numbed, and a needle will be inserted to remove a sample of tissue from inside the bone. Bitopertin is a pill taken by mouth. Participants will take the drug once a day every day for 8 months. They will start with a low dose of the drug; the dosage may increase gradually over time. They will keep a diary to record each dose. Participants will have blood tests every 4 weeks. This may be done in the clinic. Participants may also have telehealth visits; they can have blood drawn at a local lab and sent to the researchers. The bone marrow biopsy and other tests will be repeated after 8 months. Participants who have a positive response to bitopertin will be invited to enter an extended phase of the trial. They may continue to take the drug for 3 more years. Those who choose not to continue in the extended phase may have a follow-up visit 6 months after they stop taking the drug.

Conditions

Steroid-refractory Diamond-Blackfan Anemia (DBA)

Keywords

Inherited Bone Marrow Failure Syndrome; Erythroid Aplasia; Iron Homeostasis; Ribosomopathy; Heme Synthesis; Hemoglobin Synthesis

Outcome Measures

Primary Outcomes (1)

• Rate of response

  Response as demonstrated by either an increase in hemoglobin or decrease in transfusion rate, and robust response as demonstrated by transfusion independence.

  On a rolling basis (sliding window) from drug initiation until 8 months (32 weeks)

Secondary Outcomes (7)

• Rate of relapse

  Ongoing for up to 3 years, beginning 8 months (32 weeks) from drug initiation

• Long-term safety of drug

  Ongoing for up to 3 years, beginning 8 months (32 weeks) from drug initiation.

• Tolerability of drug

  8 months (32 weeks) from drug initiation

• Safety of drug

  8 months (32 weeks) from drug initiation

• Clonal evolution on bitopertin

  Annually for up to 3 years, beginning 8 months (32 weeks) from drug initiation

Study Arms (1)

Experimental -Bitopertin

EXPERIMENTAL

Bitopertin, up to a maximum dose of 60 mg (5 mg, 10mg, 20mg, 40mg, 60mg)

Drug: Bitopertin

Interventions

Bitopertin DRUG

Dose Escalation: Monthly (every 4 weeks) up to a maximum dose of 60 mg bitopertin (5 mg, 10mg, 20mg, 40mg, 60mg). At each monthly (4 week) interval, a complete blood count (CBC) with differential and a reticulocyte analysis (including reticulocyte hemoglobin) will be collected prior to taking the higher dose. If the absolute reticulocyte count (ARC) is 60,000 /microL or higher, the subject will hold at the current dose level (or return to that level if escalation has already occurred) for an additional 4 weeks. If, after 8 weeks at that dose, response criteria are met this will be considered the minimum effective dose (MED) and shall be the treatment dose throughout the remainder of the study unless modifications are indicated.

Experimental -Bitopertin

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all of the following criteria:
• Diamond-Blackfan anemia defined as chronic anemia presenting on or before the third year of life, associated with reticulocytopenia and greatly reduced or absent bone marrow erythroid precursors, supported by, but not requiring either:
• familial history
• gene mutation testing demonstrating a known disease-causing mutation or a mutation of disease-associated gene in combination with clinical characteristics of DBA
• Patients with late-onset DBA (diagnosed after the third year of life) may also be included if (but only if) gene mutation testing confirms a disease-causing mutation, as above.
• Clinically-significant anemia as defined as either:
• hemoglobin less than 9.0 g/dL
• red cell transfusion of at least 2 units PRBC for adults in the eight weeks prior to study enrollment
• Relapsed and/or steroid-refractory disease or patient intolerance of systemic corticosteroids
• Age \>= 18 years at the time of consent
• Although all patients without a molecular diagnosis (i.e., genetic testing positive for a disease- causing lesion) will undergo targeted gene panel testing for mutations in all known genes associated with DBA , the diagnosis of DBA is a clinical one, and as such, consent and enrollment does not require results from these genetic tests in the absence of any features that would suggest an alternative diagnosis (e.g., Fanconi Anemia, Dyskeratosis Congenita, etc.).

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Treatment with androgens (danazol or oxymetholone) or corticosteroids less than 4 weeks prior to initiating bitopertin.
• Hypersensitivity to bitopertin or its components
• Patient Health Questionnaire-8 (PHQ-8) score greater than or equal to 10 or imminent suicidal risk identified by the Columbia-Suicide Severity Rating Scale (C-SSRS) as defined as suicidal ideation with intent (grade 4 or 5) within the last year or any suicidal behavior within the last five years
• Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy
• Life expectancy of less than 3 months from any cause
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:
• Recent myocardial infarction (within last 6 months),
• Uncontrolled congestive heart failure,
• Unstable angina (within last 6 months),
• Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third-degree AV block without a pacemaker.)
• Long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome or additional risk factors for cardiac repolarization abnormality, as determined by the investigator
• Impaired cardiac function such as corrected QTc\>450msec using Fridericia correction on the screening ECG, other clinically significant cardio-vascular disease (e.g., uncontrolled hypertension, history of labile hypertension), history of known structural abnormalities (e.g. cardiomyopathy).
• Known active or uncontrolled infections not adequately responding to appropriate therapy.
• Note, HIV infection is not exclusive of trial participation if the infection is effectively controlled with medications not known to interfere with bitopertin metabolism or be metabolized by pathways known to be altered by bitopertin. HIV RNA viral load must be undetectable at the time of enrollment, and CD4 cell count must be \>= 200/microL. Patients must remain on antiretroviral therapy throughout study participation and must be periodically monitored for suppression of viral load and CD4 cell count.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Congenital Bone Marrow Failure Syndromes; Anemia, Aplastic

Interventions

(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone

Condition Hierarchy (Ancestors)

Bone Marrow Failure Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia

Study Officials

• David J Young, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2023
• First Posted: April 25, 2023
• Study Start: July 25, 2023
• Primary Completion: August 28, 2025
• Study Completion: August 28, 2025
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be made available by the end of the protocol or at the time of associated publication, whichever comes first.
• Access Criteria: BioData Catalyst is supported by NHLBI and access to data is controlled by the NHLBI Data Access Committee (DAC) utilizing the database of Genotypes and Phenotypes (dbGaP) permissions infrastructure. In order to access controlled-access data in BioData Catalyst, an investigator must have an approved Data Access Request (DAR) in dbGaP.

Locations

US (1)