Bitopertin for Diamond-Blackfan Anemia

Overseen By David J Young, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

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, which can help manage the disease. Participants will take the drug for several months, with periodic check-ups to monitor their response. Bitopertin has shown promise in improving anemia in a mouse model.

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.

How is the drug Bitopertin different from other treatments for Diamond-Blackfan Anemia?

Bitopertin is unique because it is a heme synthesis modulator, which means it works by affecting the production of heme, a component of hemoglobin, unlike other treatments that primarily focus on managing symptoms with steroids or immunosuppressants. This approach could offer a new way to address the underlying cause of anemia in Diamond-Blackfan Anemia. ^{1 2 3 4 5}

Research Team

David J Young, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

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

Hypersensitivity to bitopertin or its components

I do not have any severe illnesses that would prevent me from following the treatment plan.

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

Trial Timeline

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

Treatment Details

Interventions

• Bitopertin (GlyT1 Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Failure of immunosuppressive therapy and high-dose intravenous immunoglobulins in four transfusion-dependent, steroid-unresponsive Blackfan-Diamond anemia patients. [2021]

2. Spain pubmed.ncbi.nlm.nih.gov

[Long term evolution in Blackfan-Diamond hypoplastic anemia (author's transl)]. [2006]

3. United States pubmed.ncbi.nlm.nih.gov

Study of 22 Egyptian patients with Diamond-Blackfan anemia, corticosteroids, and cyclosporin therapy results. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Diamond-Blackfan anemia: clinical features and treatment results in 4 cases. [2013]

5. Japan pubmed.ncbi.nlm.nih.gov

Successful long-term management with low-dose prednisolone in an adult patient with Diamond-Blackfan anemia. [2017]