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

Completed · Phase 1/Phase 2

Conditions studied: Steroid-refractory Diamond-Blackfan Anemia (DBA)

In brief

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.

Key facts

Study ID: NCT05828108
Run by: National Heart, Lung, and Blood Institute (NHLBI)
People needed: 15
Starts: 2023-07-25
Expected to finish: 2025-08-28
Last updated by the study team: 2026-06-30

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

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.
Stable physiologic dose steroid replacement for adrenal insufficiency or other similar conditions is not an exclusion criterium.
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.
If drug-drug interactions between antiretroviral (e.g. HIV), antiviral (e.g., hepatitis), or antifungal medications and bitopertin are suspected (such as lopinavir, ritonavir or other strong CYP3A4 inhibitors), these must be addressed by a qualified clinical pharmacist or pharmacologist, and any changes to antiretroviral therapy need to be approved in consultation with an Infectious Disease and/or HIV specialist prior to enrollment.
Evidence for MDS or AML as defined by WHO criteria, or any active malignancy or likelihood of recurrence of malignancies within 12 months
Patients who have received chemotherapeutic treatment or other specific antineoplastic drugs or radiation therapy within 6 months of study entry
Female subjects who are nursing or pregnant (positive serum or urine beta-human chorionic gonadotrophin (beta-hCG) pregnancy test) at screening/baseline visit
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, not using highly effective methods of contraception during dosing and for 30 days after the last dose of bitopertin. Highly effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female patients on the study the vasectomized male partner should be the sole partner for that patient.
Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate

Where it is running

National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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