Luspatercept for Thalassemia

Recruiting at 41 trial locations

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

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Celgene

Must not be taking: Hydroxyurea, Immunomodulatory drugs, others

Disqualifiers: Hepatitis, HIV, Thrombosis, others

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

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: Unknown

Duration: 1 year

99 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications like hydroxyurea, erythropoiesis-stimulating agents, and some herbs or supplements must be stopped 12 to 24 weeks before joining, depending on your transfusion status.

What makes the drug Luspatercept unique for treating Thalassemia?

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

What is the purpose of this trial?

This trial is testing a drug called luspatercept in children with β-thalassemia to see if it is safe and how it works in their bodies. The study includes children who need regular blood transfusions and those who do not. Luspatercept helps the body make more red blood cells, which can lessen the need for transfusions. Luspatercept is a newly approved treatment for reducing the need for blood transfusions in adults.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for children and adolescents aged 6 to less than 18 with β-thalassemia who need regular blood transfusions. They should have a performance status score ≥50, be on transfusion treatment for at least 2 years, and agree to contraception if applicable. Excluded are those with recent major surgery, certain other health conditions or treatments, or prior exposure to similar drugs.

Inclusion Criteria

I am between 6 and 17 years old and can sign the consent form.

Willing and able to adhere to the study visit schedule and other protocol requirements

If you are a female who can have children or a male who has reached puberty, you must talk to a doctor about the effects of the study treatment on your ability to have children.

Exclusion Criteria

My kidneys do not work well.

My protein levels in urine are very high.

I received a live COVID-19 vaccine within the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive luspatercept with dose escalation and expansion cohorts for both transfusion-dependent and non-transfusion-dependent β-thalassemia participants

1 year

Long-term Treatment

Participants benefiting from the study treatment may continue luspatercept treatment for up to 5 years

Up to 5 years

Posttreatment Follow-up

Participants are monitored for safety and effectiveness after discontinuing treatment

At least 5 years from first dose or 3 years from last dose

Treatment Details

Interventions

• Luspatercept

Trial Overview The study tests the safety and how the body processes luspatercept (ACE-536) in young patients requiring regular red blood cell transfusions due to β-thalassemia. It has two parts: one for ages 12-<18 and another for ages 6-<12, each with dose escalation followed by expansion cohorts.

Participant Groups

Group I: Cohort 9: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.2 mg/kg Experimental Treatment 1 Intervention

Group II: Cohort 8: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kg Experimental Treatment 1 Intervention

Group III: Cohort 7: NTD Dose Expansion Cohort: NTD 12 to < 18 years Experimental Treatment 1 Intervention

Group IV: Cohort 6: NTD Dose Confirmation Cohort: 12 to < 18 years Luspatercept 1.0 mg/kg Experimental Treatment 1 Intervention

Group V: Cohort 5: TD Dose Escalation Cohort: 6 to <12 years Luspatercept 1.2 mg/kg Experimental Treatment 1 Intervention

Group VI: Cohort 4: TD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kg Experimental Treatment 1 Intervention

Group VII: Cohort 3: TD Dose Expansion Cohort: 12 to <18 years Luspatercept 1.0 mg/kg Experimental Treatment 1 Intervention

Group VIII: Cohort 2: TD Dose Escalation Cohort: 12 to < 18 years: Luspatercept 1.0 mg/kg Experimental Treatment 1 Intervention

Group IX: Cohort 1: TD Dose Escalation Cohort: 12 to < 18 years Luspatercept 0.75 mg/kg Experimental Treatment 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?

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

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Industry Sponsor

Trials

33

Recruited

4,300+

Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Industry Sponsor

Trials

33

Recruited

4,300+

Findings from Research

Enzyme replacement therapy with sebelipase alfa significantly improved survival rates in infants with lysosomal acid lipase deficiency (LAL-D), with 79% surviving to 12 months and 68% to 5 years, while also promoting normal growth and development.

The treatment was well tolerated, with no patients discontinuing due to adverse events, and most infusion-related reactions were mild to moderate, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies. Vijay, S., Brassier, A., Ghosh, A., et al.[2023]

A patient with mucopolysaccharidosis type VI experienced significant infusion-associated reactions after starting enzyme replacement therapy with galsulfase, which made it difficult to tolerate the recommended infusion rate.

By reducing the infusion rate and adding steroids to the premedication regimen, the patient was able to continue treatment successfully without further infusion-related reactions, demonstrating a safe and effective adjustment strategy for administering galsulfase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful management of difficult infusion-associated reactions in a young patient with mucopolysaccharidosis type VI receiving recombinant human arylsulfatase B (galsulfase [Naglazyme]). Kim, KH., Decker, C., Burton, BK.[2013]

Sebelipase alfa (Kanuma™) is an enzyme replacement therapy approved for treating lysosomal acid lipase (LAL) deficiency, which helps reduce lipid accumulation and improve related health issues like dyslipidaemia and liver abnormalities.

Administered via intravenous infusion once weekly or biweekly, sebelipase alfa received its first approval in the EU in August 2015, with additional regulatory submissions in the USA, Mexico, and Japan, indicating its global recognition as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sebelipase alfa: first global approval. Shirley, M.[2023]

A patient with mucopolysaccharidosis type VI developed nephrotic syndrome after starting enzyme replacement therapy (ERT) with recombinant human aryl sulfatase B (rhASB), indicating a potential immune response to the treatment.

Inducing immune tolerance through a combination of immunosuppressive therapies allowed for the safe resumption of ERT without worsening kidney issues, suggesting a viable strategy for managing ERT-induced renal complications in sensitized patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allo-immune membranous nephropathy and recombinant aryl sulfatase replacement therapy: a need for tolerance induction therapy. Debiec, H., Valayannopoulos, V., Boyer, O., et al.[2022]

Enzyme replacement therapy (ERT) for adults with Fabry disease showed a statistically significant decrease in left ventricular mass index (LVMI) and a reduction in the risk of proteinuria, indicating potential benefits in heart health and kidney function over time.

In children with Fabry disease, the study found no significant evidence of effectiveness from ERT, suggesting that the treatment may not have the same benefits for younger patients as it does for adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS-LSD cohort study. Anderson, LJ., Wyatt, KM., Henley, W., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies. [2023]

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

Successful management of difficult infusion-associated reactions in a young patient with mucopolysaccharidosis type VI receiving recombinant human arylsulfatase B (galsulfase [Naglazyme]). [2013]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Sebelipase alfa: first global approval. [2023]

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

Allo-immune membranous nephropathy and recombinant aryl sulfatase replacement therapy: a need for tolerance induction therapy. [2022]

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

Long-term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS-LSD cohort study. [2022]