Luspatercept for Thalassemia

Recruiting at 53 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Hydroxyurea

Disqualifiers: Pregnancy, Uncontrolled hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

249 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that participants should not have used hydroxyurea treatment within 12 to 24 weeks before joining, depending on their transfusion status. It's best to discuss your specific medications with the trial team.

What makes the drug Luspatercept unique for treating Thalassemia?

Luspatercept is unique for treating Thalassemia because it works by enhancing red blood cell production, which is different from traditional treatments that often focus on managing symptoms or complications. This mechanism offers a novel approach to reducing the need for blood transfusions in patients with Thalassemia. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of the study is to evaluate the efficacy and safety of luspatercept plus best supportive care (BSC) vs placebo plus BSC on anemia in adult participants with α-thalassemia hemoglobin H (HbH) disease and determine the safety and drug levels in adolescent participants.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with α-thalassemia hemoglobin H (HbH) disease, which may include those dependent on blood transfusions. Participants should have a stable health status (ECOG score of 0 or 1), and not be at risk of pregnancy or causing one. Exclusions include other types of anemia, bleeding disorders, recent unrelated hemolysis episodes, significant medical conditions that could affect study participation, prior gene therapy for α-thalassemia, recent use of certain medications like ESAs, and history of DVT or stroke.

Inclusion Criteria

I am a teenager with α-thalassemia HbH disease, need few blood transfusions, and have low hemoglobin.

I am a teenager with α-thalassemia HbH disease and have needed regular blood transfusions for at least 2 years.

I am a teenager who can do most activities without help.

Exclusion Criteria

I do not have anemia caused by diet, chronic illness, or immune system issues.

I do not have a condition that causes frequent bleeding.

I have not had a bone marrow transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive luspatercept or placebo plus best supportive care for anemia management

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for long-term safety and efficacy outcomes

Up to 108 weeks

Treatment Details

Interventions

• Luspatercept
• Placebo

Trial Overview The trial is testing the effectiveness and safety of Luspatercept plus best supportive care versus a placebo plus best supportive care in managing anemia in individuals with α-thalassemia HbH disease. The goal is to see if Luspatercept can improve their condition compared to not receiving the drug.

Participant Groups

Group I: Transfusion Dependent (TD): Luspatercept + Best supportive care (BSC) Experimental Treatment 1 Intervention

Group II: Non-transfusion Dependent (NTD): Luspatercept + BSC Experimental Treatment 1 Intervention

Group III: Adult TD Cohort: Placebo + BSC Placebo Group 1 Intervention

Group IV: Adult NTD Cohort: Placebo + BSC Placebo Group 1 Intervention

Luspatercept is already approved in United States, European Union for the following indications:

Approved in United States as Reblozyl for:

• Anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions
• Anemia in adults with transfusion-dependent anemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts

Approved in European Union as Reblozyl for:

• Anemia in adults with transfusion-dependent beta thalassemia
• Anemia in adults with transfusion-dependent anemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Alemtuzumab has shown significant efficacy in treating fludarabine-refractory chronic lymphocytic leukemia, achieving remissions with undetectable residual disease in patients, including those with poor prognostic factors.

Current research is exploring new applications for alemtuzumab, such as combining it with other treatments, using it for maintenance therapy, and purging bone marrow before transplantation, with several clinical trials underway to assess these strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutic strategies with alemtuzumab for chronic lymphocytic leukemia. Rai, KR.[2017]

The novel TCR ligand RTL342M showed rapid and significant reversal of symptoms in a mouse model of multiple sclerosis (EAE), with effective doses as low as 2 micrograms, indicating its high potency compared to traditional treatments.

RTL342M not only prevented the onset of disease when administered before symptoms but also effectively treated relapses, suggesting its potential as a versatile therapy for managing multiple sclerosis in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monomeric DR2/MOG-35-55 recombinant TCR ligand treats relapses of experimental encephalomyelitis in DR2 transgenic mice. Link, JM., Rich, CM., Korat, M., et al.[2014]

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, shows promising efficacy in treating severe aplastic anemia (SAA), particularly in relapsed and refractory cases, with a response rate of 56% and a 3-year survival rate of 86%.

In comparison to rabbit antithymocyte globulin (ATG), alemtuzumab demonstrated similar response rates in refractory SAA (37% vs. 33%), but with a higher 3-year survival rate of 83% for alemtuzumab, suggesting it may be a viable alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia. Scheinberg, P., Nunez, O., Weinstein, B., et al.[2021]

In a small study of three patients with pure red cell aplasia, low-dose subcutaneous alemtuzumab (15 mg) was administered 2-3 times a week for 3 to 4 weeks, resulting in a significantly faster response time of 17 days compared to at least 61 days with standard first-line therapies.

The treatment was well-tolerated with no serious side effects, and patients experienced a mean remission duration of 13 months, suggesting that low-dose alemtuzumab is a safe and effective option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose subcutaneous alemtuzumab is a safe and effective treatment for chronic acquired pure red cell aplasia. Chow, JK., Chan, TK.[2018]

RTL1000, a human recombinant T cell receptor ligand, was found to be safe and well tolerated in a Phase 1 study involving 34 subjects with multiple sclerosis, even at doses up to 200 mg.

This treatment showed potential for reversing clinical and histological signs of experimental autoimmune encephalomyelitis (EAE), suggesting it could offer a new way to manage MS without causing global immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RTL therapy for multiple sclerosis: a Phase I clinical study. Offner, H., Sinha, S., Burrows, GG., et al.[2022]

References

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

Novel therapeutic strategies with alemtuzumab for chronic lymphocytic leukemia. [2017]

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

Monomeric DR2/MOG-35-55 recombinant TCR ligand treats relapses of experimental encephalomyelitis in DR2 transgenic mice. [2014]

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

Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia. [2021]

4. China pubmed.ncbi.nlm.nih.gov

Low-dose subcutaneous alemtuzumab is a safe and effective treatment for chronic acquired pure red cell aplasia. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

RTL therapy for multiple sclerosis: a Phase I clinical study. [2022]