Long-Term Safety of Luspatercept for Blood Disorders

Recruiting in Palo Alto (17 mi)

+188 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Celgene

Must be taking: Luspatercept

Disqualifiers: Pregnancy, Breastfeeding, Significant medical condition, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following participants: * Participants receiving luspatercept on a parent protocol at the time of their transition to the rollover study, who tolerate the protocol-prescribed regimen in the parent trial and, in the opinion of the investigator, may derive clinical benefit from continuing treatment with luspatercept * Participants in the follow-up phase previously treated with luspatercept or placebo in the parent protocol will continue into long-term post-treatment follow-up in the rollover study until the follow-up commitments are met * The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Participants will enter transition phase and depending on their background will enter either the treatment phase or the Long-term Post-treatment Follow-up (LTPTFU) phase * Transition Phase is defined as one Enrollment visit * Treatment Phase: For participants in luspatercept treatment the dose and schedule of luspatercept in this study will be the same as the last dose and schedule in the parent luspatercept study. This does not apply to participants that are in long-term follow-up from the parent protocol * Follow-up Phase includes: - 42 Day Safety Follow-up Visit * During the Safety Follow up, the participants will be followed for 42 days after the last dose of luspatercept, for the assessment of safety-related parameters and adverse event (AE) reporting - Long-term Post-treatment Follow-up (LTPTFU) Phase * Participants will be followed for overall survival every 6 months for at least 5 years from first dose of luspatercept in the parent protocol, or 3 years of post-treatment from last dose, whichever occurs later, or until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Participants will also be monitored for progression to AML or any malignancies/pre-malignancies. New anticancer or disease related therapies should be collected at the same time schedule Participants transitioning from a parent luspatercept study in post-treatment follow-up (safety or LTPTFU) will continue from the same equivalent point in this rollover study. The ACE-536-LTFU-001 rollover study will be terminated, and relevant participants will discontinue from the study when all participants fulfill 5 years on the study, including treatment and follow-up.

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.

How is the drug Luspatercept unique for treating blood disorders?

Luspatercept is unique because it works by enhancing the maturation of red blood cells, which is different from other treatments that may focus on suppressing the immune system or targeting specific proteins involved in blood disorders. This mechanism can help improve anemia in patients with certain blood disorders. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Luspatercept (Protein Therapy)

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).

Participant Groups

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.

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

Findings from Research

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 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 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]

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 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]

References

1. England 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. [2018]

2. Canada 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). [2021]

3. United States 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. [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial. [2015]

5. Italy pubmed.ncbi.nlm.nih.gov

Tacrolimus is effective for lupus nephritis patients with persistent proteinuria. [2022]