What side effects are associated with this type of intervention?

Common treatments for Beta Thalassemia include erythroid maturation agents like Luspatercept, blood transfusions, and iron chelation therapy. Luspatercept may cause side effects such as fatigue, headache, bone pain, and increased liver enzymes. Blood transfusions can lead to complications like iron overload, which necessitates iron chelation therapy. Iron chelation therapy itself can cause side effects such as gastrointestinal disturbances, liver and kidney dysfunction, and auditory and visual impairments. It is important to monitor patients closely to manage these potential side effects effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Beta Thalassemia, including blood transfusions and iron chelation therapy to manage iron overload. More recently, Luspatercept, an erythroid maturation agent, has been approved to treat anemia in adult patients with Beta Thalassemia who require regular red blood cell transfusions. This approval marks a significant advancement as it directly targets ineffective erythropoiesis, a hallmark of Beta Thalassemia, thereby reducing the need for transfusions.

What other types of research exist?

Promising novel alternatives to Luspatercept for Beta Thalassemia patients may include gene therapies, such as CRISPR-Cas9 based treatments, and other erythropoiesis-stimulating agents. Additionally, novel pharmacological agents targeting different pathways involved in erythropoiesis and iron metabolism are under investigation. Consulting recent clinical trial databases and literature will provide the most current options.

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Protein Therapeutics

Luspatercept for Thalassemia

Q: What is the mechanism of action of this treatment?

Beta Thalassemia treatments primarily aim to address ineffective erythropoiesis and anemia. Luspatercept, an erythroid maturation agent, works by promoting the maturation of red blood cells, thereby increasing hemoglobin levels and reducing the need for blood transfusions. This is crucial for Beta Thalassemia patients as it helps manage chronic anemia and reduces complications associated with frequent transfusions, such as iron overload. Other common treatments include regular blood transfusions to maintain adequate hemoglobin levels and iron chelation therapy to manage iron overload. These treatments collectively improve the quality of life and overall prognosis for Beta Thalassemia patients.

Phase 2

Recruiting

Research Sponsored by Celgene

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant must be 6 years to < 18 years of age at the time of signing the informed consent form (ICF)/informed assent form (IAF).

History of regular transfusions for at least 2 years

Must not have

Proteinuria ≥ Grade 3 or urine albumin/creatinine ratio > 129 mg/mmol of creatinine

Use of hydroxyurea treatment ≤ 24 weeks prior to enrollment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 weeks prior to enrollment; treatment period and up to end of treatment including long-term treatment period - up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects of luspatercept in this pediatric population aren't listed here, common ones may include reactions at injection site, headache, muscle pains or cramps; more serious risks could involve blood pressure changes or abnormal liver function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I have been receiving regular blood transfusions for at least 2 years.

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I am between 6 and 17 years old.

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I have been diagnosed with β-thalassemia.

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I have been diagnosed with β-thalassemia or Hemoglobin E/β-thalassemia.

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I have received 4 or more blood transfusions in the last 6 months without a break of 42 days or more.

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I can do most activities but may need help.

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I can do most activities myself, but may need help.

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I have had at least 4 blood transfusions in the last 6 months without a break of more than 6 weeks.

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I agree to use a condom or practice true abstinence.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My protein levels in urine are very high.

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I have used hydroxyurea within the last 24 weeks.

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My high blood pressure is not under control.

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I haven't used any experimental drugs or devices in the last 28 days.

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I have an active hepatitis C or B infection, or I am HIV positive.

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I have previously been treated with sotatercept or luspatercept.

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My diabetes has been poorly controlled in the last 6 months.

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I need treatment to manage growths related to my bone marrow condition.

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I have been diagnosed with Hemoglobin S/β-thalassemia or α-thalassemia.

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I have significant damage to a major organ.

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I have had or am scheduled for a stem cell transplant or gene therapy.

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I have not had major surgery in the last 3 months.

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I have been on blood thinner medication for less than 28 days before joining.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 weeks prior to enrollment; treatment period and up to end of treatment including long-term treatment period - up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 weeks prior to enrollment; treatment period and up to end of treatment including long-term treatment period - up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 weeks prior to enrollment; treatment period and up to end of treatment including long-term treatment period - up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Determination of the Recommended Dose (RD

Pharmacokinetics (PK) - CL/F

Pharmacokinetics (PK) - Vd/F

+3 more

Secondary study objectives

Immunogenicity

Mean change from baseline in mean daily dose of iron chelation therapy (ICT)

Mean change from baseline in serum ferritin

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: Cohort 9: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.2 mg/kgExperimental Treatment1 Intervention

Group II: Cohort 8: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kgExperimental Treatment1 Intervention

Group III: Cohort 7: NTD Dose Expansion Cohort: NTD 12 to < 18 yearsExperimental Treatment1 Intervention

Group IV: Cohort 6: NTD Dose Confirmation Cohort: 12 to < 18 years Luspatercept 1.0 mg/kgExperimental Treatment1 Intervention

Group V: Cohort 5: TD Dose Escalation Cohort: 6 to <12 years Luspatercept 1.2 mg/kgExperimental Treatment1 Intervention

Group VI: Cohort 4: TD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kgExperimental Treatment1 Intervention

Group VII: Cohort 3: TD Dose Expansion Cohort: 12 to <18 years Luspatercept 1.0 mg/kgExperimental Treatment1 Intervention

Group VIII: Cohort 2: TD Dose Escalation Cohort: 12 to < 18 years: Luspatercept 1.0 mg/kgExperimental Treatment1 Intervention

Group IX: Cohort 1: TD Dose Escalation Cohort: 12 to < 18 years Luspatercept 0.75 mg/kgExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ACE-536

2011

Completed Phase 1

~40

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Beta Thalassemia treatments primarily aim to address ineffective erythropoiesis and anemia. Luspatercept, an erythroid maturation agent, works by promoting the maturation of red blood cells, thereby increasing hemoglobin levels and reducing the need for blood transfusions. This is crucial for Beta Thalassemia patients as it helps manage chronic anemia and reduces complications associated with frequent transfusions, such as iron overload. Other common treatments include regular blood transfusions to maintain adequate hemoglobin levels and iron chelation therapy to manage iron overload. These treatments collectively improve the quality of life and overall prognosis for Beta Thalassemia patients.

Colla corii asini might upregulate ZNF471 and THOC5 by KRAB domain-containing zinc-finger protein pathway and THO complex subunit 5 pathway to improve anemia of pregnant women with β-thalassemia.