Long-Term Safety of Luspatercept for Blood Disorders

Recruiting at 183 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celgene

Must be taking: Luspatercept

Disqualifiers: Pregnancy, Breastfeeding, Significant medical condition, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

665 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term safety of luspatercept (also known as Reblozyl) for individuals with certain blood disorders. It aims to assess the effectiveness of luspatercept over time and identify any safety concerns during extended use. Participants who were part of a previous luspatercept study and continue to benefit from the treatment or were in the follow-up phase are suitable for this trial. Eligible participants have experience with the treatment and still meet the initial study requirements. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that any medications or procedures prohibited in the parent luspatercept protocol cannot be used. It's best to discuss your current medications with the study team to ensure they are allowed.

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

In previous studies, luspatercept has consistently proven safe. Research indicates that most patients tolerate it well. For example, one study found no new safety concerns over a period of up to five years. Another study showed that in adults with beta thalassemia (a blood disorder), about 3.6% of patients experienced blood clots, such as deep vein thrombosis, though this rate is relatively low.

Overall, luspatercept increases hemoglobin levels and reduces the need for blood transfusions. These benefits have been observed without significant, unexpected side effects. Prospective trial participants might find this information reassuring regarding luspatercept's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for blood disorders that often rely on regular blood transfusions or medications to boost red blood cell production, Luspatercept offers a novel approach. It works by targeting and inhibiting specific proteins involved in red blood cell maturation, potentially leading to more effective and sustained production of healthy red blood cells. This unique mechanism of action sets it apart from traditional therapies, and researchers are excited about its potential to reduce the need for frequent transfusions and improve quality of life for patients. Additionally, Luspatercept is administered via a convenient subcutaneous injection, making it a more straightforward option for patients compared to some of the existing treatments.

What is the effectiveness track record for luspatercept in treating blood disorders?

Research has shown that luspatercept, the investigational treatment in this trial, effectively treats anemia, particularly in patients with certain blood disorders. Studies have found that it reduces the need for red blood cell transfusions in many patients. Specifically, many patients who relied on transfusions managed to go without them for at least 8 weeks. Luspatercept also improved anemia symptoms and reduced the need for transfusions in patients with conditions like myelofibrosis, a type of bone marrow disorder. Overall, the safety profile of luspatercept aligns with previous studies, highlighting its potential benefits for patients with anemia-related conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

Adults over 18 who have been part of previous luspatercept trials and may benefit from continued treatment. They must understand and consent to study requirements, adhere to visit schedules, and if applicable, use contraception. Excluded are those with conditions that could skew data or at high risk from participation, pregnant/breastfeeding women, or those not compliant with the parent trial.

Inclusion Criteria

Participant demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.

Participant has been participating in a luspatercept trial and continues to fulfill all the requirements of the parent protocol and the participant has been either: Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR Assigned to placebo arm in the parent protocol (at the time of unblinding or in follow-up) and should cross over to luspatercept treatment, OR Assigned to the Follow-up Phase of the parent protocol, previously treated with luspatercept or placebo in the parent protocol who shall continue into Long-term Post-treatment Follow-up Phase in the rollover study until the follow-up commitments are met (unless requirements are met as per parent protocol to crossover to luspatercept treatment).

I can have children, will test for pregnancy, and follow the study's birth control rules.

Exclusion Criteria

Participant has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

I do not have any health, mental, or legal issues preventing me from joining the study.

I am currently pregnant or breastfeeding.

Timeline for a Trial Participant

Transition

Participants transition from the parent protocol to the rollover study

1 visit

1 visit (in-person)

Treatment

Participants receive luspatercept treatment with the same dose and schedule as in the parent study

42 Day Safety Follow-up

Participants are monitored for safety-related parameters and adverse event reporting for 42 days after the last dose of luspatercept

6 weeks

Long-term Post-treatment Follow-up (LTPTFU)

Participants are followed for overall survival and monitored for progression to AML or other malignancies every 6 months for at least 5 years

At least 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Luspatercept

Trial Overview The long-term safety of luspatercept is being tested in patients transitioning from earlier trials. The study has three phases: Transition (enrollment), Treatment (same dose as before), and Follow-up (42-day safety check and up to 5 years of survival tracking).

How Is the Trial Designed?

Group I: ACE-536 Experimental Treatment 1 Intervention

Luspatercept will be administered as a subcutaneous (SC) injection to participants by the study staff at the clinical site and administration will be documented in the subject's source record.

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?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

In a long-term study of subcutaneous abatacept (ABA) involving 1372 patients with rheumatoid arthritis who had inadequate responses to methotrexate, the treatment was found to be well-tolerated with a low incidence of serious adverse events, including serious infections and malignancies.

Efficacy was maintained over approximately 3.5 years, with high response rates (80.2% for ACR20) indicating that ABA continues to effectively manage symptoms of rheumatoid arthritis in patients who previously did not respond well to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial. Genovese, MC., Tena, CP., Covarrubias, A., et al.[2015]

In a study of 1355 patients with lupus nephritis treated with tacrolimus for 5 years, the treatment was found to be well tolerated, with serious adverse drug reactions occurring mainly in the first 28 weeks and no significant increase in risk over time.

Tacrolimus significantly improved key health markers related to lupus nephritis, such as urine protein levels and anti-dsDNA antibody levels, while maintaining a low cumulative rate of progression to renal failure (6.6% at Year 5) and manageable relapse rates (30.6% at Year 5).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Safety and Effectiveness of Tacrolimus in Patients With Lupus Nephritis: 5-year Interim Postmarketing Surveillance Study in Japan (TRUST). Takeuchi, T., Wakasugi, N., Uno, S., et al.[2021]

In a study of 23 Japanese patients with lupus nephritis, tacrolimus was found to be safe and well tolerated, with no adverse reactions leading to discontinuation of treatment over a 6-month period.

Tacrolimus significantly improved proteinuria and serum albumin levels, as well as other markers of inflammation, indicating its potential efficacy as a maintenance therapy for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus is effective for lupus nephritis patients with persistent proteinuria. Uchino, A., Tsukamoto, H., Nakashima, H., et al.[2022]

Belimumab, a monoclonal antibody targeting B cell activating factor (BAFF), has been shown to be effective in treating Systemic Lupus Erythematosus (SLE), with significant results from trials like BLISS-52 and BLISS-76 involving patients with active disease.

Both intravenous (10 mg/kg) and subcutaneous (200 mg weekly) formulations of belimumab demonstrated similar efficacy and safety profiles, leading to its approval for use in SLE patients, although those with severe lupus nephritis and central nervous system involvement were not included in the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous and intravenous belimumab in the treatment of systemic lupus erythematosus: a review of data on subcutaneous and intravenous administration. Poh, YJ., Baptista, B., D'Cruz, DP.[2018]

In a long-term extension phase of up to 7 years involving 153 patients with juvenile idiopathic arthritis (JIA), abatacept treatment demonstrated sustained efficacy, with significant improvements in disease response measures maintained over time.

The safety profile of abatacept improved during the long-term treatment phase, with a notable decrease in the incidence of adverse events, serious infections, and autoimmune events compared to the initial treatment phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years. Lovell, DJ., Ruperto, N., Mouy, R., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/8/17/4511/516341/Safety-and-efficacy-of-luspatercept-for-the

Safety and efficacy of luspatercept for the treatment of anemia ... Median time to anemia response was 63.0 days (range, 41-68) and 63.5 days (range, 42-85) in cohort 1 and cohort 3A, respectively.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38820422/

Safety and efficacy of luspatercept for the treatment ... In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0145212624001905

Real-world impact of luspatercept on red blood cell ... Luspatercept reduced transfusion dependency and limited use of other medications. Most transfusion-dependent patients achieved 8-week transfusion-independence.

4. reblozyl.com reblozyl.com/mds/how-reblozyl-works/first-line-results

First Line Results - REBLOZYL® (luspatercept-aamt) Learn about the first-line treatment results and side effects of REBLOZYL® (luspatercept-aamt) for patients with anemia in myelodysplastic syndromes (MDS).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03682536

NCT03682536 | A Study to Compare the Efficacy and ... The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36505885/

Long-term safety and erythroid response with luspatercept ... Luspatercept was associated with sustained increases in hemoglobin levels in NTD patients and sustained transfusion burden reductions in TD patients.

7. reblozylpro.com reblozylpro.com/mds-first-line/safety

REBLOZYL® (luspatercept-aamt) First Line Safety | For HCPs In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) of REBLOZYL-treated patients. TEEs included deep vein ...

8. ashpublications.org ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025016554/546988/Efficacy-and-safety-of-luspatercept-in-non

Efficacy and safety of luspatercept in non-transfusion ... Luspatercept was well tolerated in the study population and had a long-term safety profile that was consistent with previous studies.

9. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-INDEPENDENCE-Trial-for-Reblozyl-luspatercept-aamt-in-Adult-Patients-with-Myelofibrosis-Associated-Anemia/default.aspx

Corporate news details In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) of REBLOZYL-treated patients. TEEs included ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9671752/

Long-Term Efficacy and Safety of Luspatercept for Anemia ... Median duration of luspatercept exposure was 315 days (range, 21-1,934 days). No new safety signals emerged. HI-E was observed in 53.7% of ...