Bitopertin for Diamond-Blackfan Anemia

Overseen By David J Young, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: Androgens, Corticosteroids, Antivirals, others

Disqualifiers: Cardiac disease, Active infections, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 32 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called bitopertin for individuals with Diamond-Blackfan anemia (DBA), a condition where the bone marrow fails to produce enough red blood cells, causing severe chronic anemia. The aim is to determine if bitopertin, taken as a daily pill for eight months, can enhance red blood cell production and reduce the need for frequent blood transfusions. Individuals diagnosed with DBA, experiencing significant anemia, and finding current treatments ineffective or intolerable might be suitable candidates for this study. Participants will undergo regular blood tests and health check-ups to monitor their response to the treatment. As a Phase 1, Phase 2 trial, this research focuses on understanding how bitopertin works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that participants stop taking androgens or corticosteroids at least 4 weeks before starting the new drug. If you are on other medications, especially for HIV or other conditions, you may need to consult with a specialist to ensure there are no interactions with the trial drug.

Is there any evidence suggesting that bitopertin is likely to be safe for humans?

Research shows that bitopertin, a drug being tested for Diamond-Blackfan anemia (DBA), is generally well-tolerated. In earlier studies, researchers tested bitopertin for different conditions and found it safe for humans. Although it wasn't effective for treating schizophrenia, no major safety issues emerged.

Bitopertin blocks a specific protein that affects blood production, which might help manage DBA. While the drug is still under study, its previous testing in humans provides some understanding of its safety, potentially leading to fewer unexpected side effects for participants. However, as with any new treatment, some risk remains, so careful monitoring during the trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Diamond-Blackfan Anemia, which often involve blood transfusions and corticosteroids, Bitopertin offers a novel approach by targeting the glycine uptake pathway. Researchers are excited about Bitopertin because it works by inhibiting the glycine transporter, potentially increasing heme production and improving red blood cell formation. This new mechanism of action could provide an alternative option for patients who do not respond well to existing therapies, offering hope for more effective management of the condition.

What evidence suggests that bitopertin might be an effective treatment for Diamond-Blackfan anemia?

Research has shown that bitopertin, which participants in this trial will receive, may help treat Diamond-Blackfan anemia (DBA) by improving red blood cell production. In lab studies, bitopertin increased red blood cell growth in DBA samples and reduced anemia symptoms in mice with the disease. The drug blocks glycine absorption, which helps lower harmful heme levels in the blood. These early results suggest that bitopertin could be a promising treatment for DBA. ^{1 6 7 8 9}

Who Is on the Research Team?

David J Young, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

Adults aged 18+ with Diamond-Blackfan anemia (DBA), particularly those who have chronic severe anemia or are dependent on red blood cell transfusions. It's for patients whose DBA is steroid-refractory, meaning steroids don't work well anymore, or they can't tolerate them. Participants must not be at risk of suicide, have certain heart conditions, active infections poorly controlled by therapy, or a history of specific malignancies.

Inclusion Criteria

I was diagnosed with Diamond-Blackfan anemia before age 3, have low red blood cell counts, and either a family history or a confirmed gene mutation.

I was diagnosed with DBA after age 3 and have a confirmed gene mutation.

I have severe anemia or needed a blood transfusion recently.

Exclusion Criteria

Life expectancy of less than 3 months from any cause

Hypersensitivity to bitopertin or its components

PHQ-8 score greater than or equal to 10 or imminent suicidal risk

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants take bitopertin daily for 8 months with dose escalation based on tolerance

32 weeks

Blood tests every 4 weeks, in-person or telehealth visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

1 follow-up visit (in-person)

Extension

Participants with a positive response may continue bitopertin for up to 3 more years

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bitopertin

Trial Overview The trial tests Bitopertin, a pill taken daily for 8 months to treat DBA. Dosage may increase over time based on response. The study includes initial screening with physical exams and blood tests followed by regular check-ups every four weeks through clinic visits or telehealth options. Successful participants may continue in an extended phase for up to three additional years.

How Is the Trial Designed?

Group I: Experimental -Bitopertin Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving four transfusion-dependent patients with Blackfan-Diamond anemia who did not respond to steroids, treatment with antithymocyte globulin (ATG) and methylprednisolone resulted in only one transient response.

None of the patients showed improvement with high-dose intravenous immunoglobulins (HDIg) or cyclosporin A (CSA), indicating that these treatments may not be effective for steroid-unresponsive BDA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of immunosuppressive therapy and high-dose intravenous immunoglobulins in four transfusion-dependent, steroid-unresponsive Blackfan-Diamond anemia patients. Bejaoui, M., Fitouri, Z., Sfar, MT., et al.[2021]

In a report of six cases of Blackfan-Diamond hypoplastic anemia, all patients exhibited severe anemia and reticulopenia, with treatment initiated primarily in infancy.

High-dose Dexamethasone treatment led to a partial response in all cases, while deferroxamine was used to manage hemosiderosis, indicating a potential therapeutic approach for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long term evolution in Blackfan-Diamond hypoplastic anemia (author's transl)]. García-Miguel, P., Muñoz Villa, A., Hurtado Ruano, T., et al.[2006]

A 43-year-old man with Diamond-Blackfan anemia (DBA) maintained a stable hemoglobin level of 9 g/dl using low-dose prednisolone (6 mg/day) and cyclosporine, which helped improve his quality of life without severe side effects.

While hematopoietic stem cell transplantation is the only curative option for DBA, it carries significant risks; thus, low-dose prednisolone may be a safer alternative for managing symptoms and enhancing patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful long-term management with low-dose prednisolone in an adult patient with Diamond-Blackfan anemia. Ogasawara, T., Kawauchi, K., Mori, N., et al.[2017]

In a study of 22 patients with Diamond-Blackfan anemia, only 22.7% responded to corticosteroid treatment, highlighting the limited efficacy of prednisolone in this condition.

Among steroid-resistant patients, 50% responded positively to cyclosporin-A (CSA) therapy, suggesting that CSA could be an effective alternative treatment before considering blood transfusions or further complications from corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of 22 Egyptian patients with Diamond-Blackfan anemia, corticosteroids, and cyclosporin therapy results. El-Beshlawy, A., Ibrahim, IY., Rizk, S., et al.[2019]

In a study of four children with Diamond-Blackfan anemia, all patients achieved complete hematological remission after treatment, with a median follow-up of 59 months, indicating the long-term efficacy of the interventions used.

Initial treatment with prednisolone was effective in one child, while others required dexamethasone or cyclosporin, highlighting the need for tailored treatment approaches in managing this rare condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diamond-Blackfan anemia: clinical features and treatment results in 4 cases. Naithani, R., Chandra, J., Narayan, S., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05828108

Study of the Selective GlyT1 Inhibitor Bitopertin for Steroid- ... Background: Diamond-Blackfan anemia (DBA) is an inherited disease that affects the bone marrow. People with DBA have chronic anemia that can be severe.

2. ashpublications.org ashpublications.org/bloodrci/article/doi/10.1016/j.brci.2025.100010/537331/Restricting-glycine-uptake-with-bitopertin

Restricting glycine uptake with bitopertin improves ... Bitopertin reduces heme synthesis, increases the erythroid differentiation of DBA cells in vitro, and improves anemia in a murine DBA model.

3. ir.discmedicine.com ir.discmedicine.com/static-files/66785cb5-73ff-475b-ba76-70770a815057

Clinical Data Updates: Bitopertin and DISC-0974 Diamond-Blackfan Anemia – Initiated July '23. Anemia of Myelofibrosis (MF) – Initiated June '22. Anemia of Non-Dialysis Dependent Chronic ...

4. withpower.com withpower.com/trial/phase-2-steroid-refractory-diamond-blackfan-anemia-dba-4-2023-d1ded

Bitopertin for Diamond-Blackfan Anemia · Info for Participants This trial tests bitopertin, a daily pill, in adults with Diamond-Blackfan anemia. The drug aims to reduce harmful levels of heme in the blood, ...

5. ir.discmedicine.com ir.discmedicine.com/news-releases/news-release-details/disc-medicine-announces-first-patient-enrolled-phase-12-clinical

News Release Details The first patient has been enrolled in the National Institutes of Health-sponsored Phase 1/2 clinical trial of bitopertin in Diamond-Blackfan anemia (DBA).

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1355/499264/Preclinical-Studies-of-the-GlyT1-Inhibitor

Preclinical Studies of the GlyT1 Inhibitor Bitopertin in Diamond ... In ~60% of patients, the anemia responds to corticosteroid therapy, leaving an unmet need for safe and effective treatment. In DBA, the ...

7. discmedicine.com discmedicine.com/our-pipeline/bitopertin/

Bitopertin (GlyT1 Inhibitor) for Erythropoietic Porphyrias Bitopertin is a clinical-stage, first-in-class, oral small molecule inhibitor of glycine transporter 1 (GlyT1), a key target to modulate heme biosynthesis.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123079582

Preclinical Studies of the GlyT1 Inhibitor Bitopertin in ... Bitopertin is an investigational oral small-molecule inhibitor of GlyT1. In Phase 3 clinical studies of schizophrenia, it was found to be ineffective but ...

9. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=001528-H&&query=Bone%20Marrow%20Failure%20Syndrome

Protocol Details Background: Diamond-Blackfan anemia (DBA) is an inherited disease that affects the bone marrow. People with DBA have chronic anemia that can be severe.