Study to Evaluate the Long- Term Safety and Efficacy of Luspatercept in Subjects Who Received at Least One Dose of Luspatercept in the Compassionate Use Phase (LUSPA001)

Observational Study to Evaluate the Long- Term Safety and Efficacy of Luspatercept in Subjects Who Received at Least One Dose of Luspatercept in the "Compassionate" Use Phase

Luspatercept represents the first and only erythroid maturation agent (EMA) approved by the European Commission (EC) and the Food and Drug Administration (FDA) capable of enhancing advanced erythrocyte maturation.

The efficacy of luspatercept was demonstrated in the phase III clinical trial called "BELIEVE." More than 200 Italian patients with transfusion- dependent beta thalassemia aged ≥18 years who had no approved therapeutic alternatives to improve their clinical course were considered eligible for the 'compassionate' use program related to luspatercept and most of them received at least one dose of the drug before it was dispensed by the National Health System (NHS), after approval by the pharmaceutical company and the Ethics Committee of the Clinical Center in which they were being followed.

Study Overview

• Status: Active, not recruiting
• Conditions: Thalassemia Major
• Intervention / Treatment: Drug: Luspatercept (ACE-536)

Detailed Description

One month after the publication in the Official Gazette of the Italian Republic of the AIFA determination of price and reimbursement for the treatment indication covered by the program, those who were still on treatment and were, in clinical judgment, eligible to continue it, continued to receive the drug through dispensation by the NHS.

Because access to the compassionate phase was less restrictive than access to that in formal clinical trials and the patients included particularly representative of real life, collecting data on clinical characteristics at baseline, safety, and efficacy is critical to enriching the information available on this new therapy. Continuing to collect efficacy, safety, and tolerability information beyond the compassionate phase is also essential for a more complete and accurate assessment, given the short duration of 'compassionate' treatment for a portion of the patients under study.

• Study Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

Study Locations

• Italy
  • CA
    • Cagliari, CA, Italy, 09121
      • University of Cagliari, Ospedale Pediatrico Microcitemico, via Jenner sn, 09121 Cagliari -

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult (male and female), living or deceased patients with transfusion-dependent beta thalassemia who received at least one dose of luspatercept during the compassionate use program.

Description

Inclusion criteria:

- Subjects who received at least one dose of luspatercept in the compassionate phase

Exclusion Criteria:

- Subjects who are not willing or able to sign the informed consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate safety of luspatercept, number of participants with treatment-related adverse events as assessed by CTCAE v4.0	To evaluate safety of luspatercept in subjects with transfusion-dependent beta thalassemia who received at least one dose of the drug in the compassionate use phase including the post- marketing authorisation phase in those who continued to receive it.	12-week interval period of luspatercept treatment.
To evaluate tolerability of luspatercept, number of participants with treatment-related adverse events as assessed by CTCAE v4.0"	To evaluate tolerability of luspatercept in subjects with transfusion-dependent beta thalassemia who received at least one dose of the drug in the compassionate use phase including the post- marketing authorisation phase in those who continued to receive it.	12-week interval period of luspatercept treatment.
To evaluate efficacy of luspatercept, Number of subjects who showed a ≥ 33% reduction from baseline in the number of transfused blood units during any 12-week interval period of luspatercept treatment	To evaluate efficacy of luspatercept in subjects with transfusion-dependent beta thalassemia who received at least one dose of the drug in the compassionate use phase including the post- marketing authorisation phase in those who continued to receive it.	12-week interval period of luspatercept treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
subjects with comorbidities, number of participants with treatment-related adverse events as assessed by CTCAE v4.0"	To evaluate safety of luspatercept in subjects with comorbidities that were exclusion criteria in formal clinical trials	12-week interval period of luspatercept treatment.
subjects with comorbidities, number of participants with treatment-related adverse events as assessed by CTCAE v4.0"	To evaluate tolerability of luspatercept in subjects with comorbidities that were exclusion criteria in formal clinical trials	12-week interval period of luspatercept treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
endocrinological changes	Number of subjects who developed endocrinologicalchanges (alterations in frequency and duration of menstrual cycle, alterations in sexual function in men, thyroid dysfunction etc )	52-week interval period of luspatercept treatment.
thromboembolic events	New cases of thromboembolic events	52-week interval period of luspatercept treatment.
factors positively affect drug response	This outcome will assess the clinical, haematological, and biochemical factors that are positively associated with a favourable drug response to luspatercept, defined as a ≥33% reduction in transfusion burden sustained for at least 12 consecutive weeks during the 52-week treatment period. Factors evaluated will include: Baseline haemoglobin level; Serum erythropoietin concentration; Reticulocyte count; Baseline transfusion burden	52-week interval period of luspatercept treatment.
factors negatively affect drug response	This outcome will evaluate clinical, haematological, biochemical, or genetic factors that are **associated with a poor or absent response** to luspatercept treatment. Non-response will be defined as failure to achieve a ≥33% reduction in transfusion burden for at least 12 consecutive weeks during the 52-week treatment period. The following factors will be assessed as potentially associated with a negative response to treatment: High baseline transfusion burden Elevated baseline serum erythropoietin levels Lack of reticulocyte increase during treatment Presence of chronic comorbidities (e.g., liver disease, endocrine disorders)	52-week interval period of luspatercept treatment.
become transfusion independent while taking the drug	Number of subjects who have not had red blood cell transfusions for at least eight consecutive weeks during treatment	52-week interval period of luspatercept treatment.

Collaborators and Investigators

• Sponsor: Fondazione per la Ricerca sulle Anemie ed Emoglobinopatie in Italia
• Investigators: Principal Investigator: RAFFAELLA ORIGA, UNIVERSITA' DI CAGLIARI

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Hematinics; Luspatercept
• Other Study ID Numbers: LUSPA001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No