LUSPARA - Luspatercept in patients affected with rare inherited anemias

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eurobloodnet Association

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

13 Feb 2026 → ongoing

Decision date (initial)

2025-10-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Bristol Myers Squibb (BMS)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To evaluate in patients with rare anemias, the effect of luspatercept on erythroid response at 12 weeks, ie reduction of transfusion burden which include either transfusion independence or significant reduction in the transfusion burden or increase in hemoglobin level as reported in thalassemia patients [4, 6]. The erythroid response at 12 weeks will be evaluated in each patient groups (CSA, CDA, NTD-DBA).

Secondary objectives 1

1. To assess the impact of luspatercept treatment on hemoglobin level and for transfusion dependent (TD) patients on transfusion burden

Conditions and MedDRA coding

Inherited anemias

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient affected with a rare constitutional anemia including. : ✔constitutional non syndromic sideroblastic anemia (CSA) including those due to germline mutation in ALAS2, SLC25A38, SLC19A2, GLRX5, HSPA9 and also more rare cases with other mutations. . Patients without genetic diagnosis (currently up to 30% of CSa patients may be included after approval of PI and geneticists ✔constitutional dyserythropïetic anemias CDA (type I and II) Diamond-Blackfan anemia not requiring regular transfusion support (NTD-DBA) (therapeutic independence or with continuous steroid therapy); 2 subgroups should be considered: RPS19 versus other genetic subgroups (mainly RPL5, RPL11 and RPS26 variants). Inclusions will be considered in order to have at least 3 patients in each subgroup before to expand inclusions
2. For diseases of the three subtypes (CSA, CDA, and DBA-NTD), diagnosis must be supported genetically by presence of ACMG class 4 or 5 variant(s).
3. Age ≥18 years at the first screening
4. For CSA and CDA, both Transfusion dependent (TD) patients and Non Transfusion dependent (TD) patients may be included: ✔TD patients: transfusion-dependency definition is: 6 to 20 units of packed red cells within previous 24 weeks with no transfusion-free period of > 56 days (except for DBA patients for whom transfusion dependency is a factor of exclusion) ✔NTD patients: patients must have significant anemia e.g. hemoglobin < 10.5 gr/dl (average of at least 2 Hb measurements separated by a minimum of 7 days during screening period) occasional transfusion aloowed if ≤ 5 red-cell units per 24 weeks and red blood cell transfusion free > 8 weeks before inclusion
5. Adequate renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance ≥ 30 mL/min (MDRD formula).
6. Adequate liver function, defined by transaminases and gamma-glutamyl transferase less than 1.5 times the upper limit of normal.
7. ECOG performance status 0-2 at the time of screening.
8. Be willing and able to give written informed consent and to comply to all study procedures for the duration of the study.
9. A FCBP (female of childbearing potential) for this study was defined as a sexually mature woman who: (1) had not undergone a hysterectomy or bilateral oophorectomy; or (2) had not been naturally postmenopausal (amenorrhea following cancer therapy did not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). A FCBP participating in the study must: oHave had 2 negative pregnancy tests as verified by the investigator prior to starting the Investigational Product (IP) (unless the screening pregnancy test was done within 72 hours of Cycle 1 Day 1). She must have had agreed to ongoing a monthly pregnancy testing during the course of the study and after EOT oIf sexually active, agreed to have used, and been able to comply with, highly effective contraception** without interruption, 5 weeks prior to starting IP, during treatment with IP (including dose interruptions), and for 12 weeks after discontinuation of IP. ** Highly effective contraception was defined in this protocol as the following (information also appeared in the ICF): Hormonal contraception (eg, birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation (tying your tubes), or a partner with a vasectomy
10. Male subjects must: Have agreed to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane), during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions, and for at least 12 weeks following IP discontinuation, even if he had undergone a successful vasectomy

Exclusion criteria 18

1. DBA patients with transfusion dependency or DBA patients with non RPS19, RPS26, RPL5 or RPL11 genotype or without gene identification
2. For patients with CSA and no established genetic diagnosis, acquired sideroblastic anemia and SF3B1 variant should be excluded with non RPS19, RPS26, RPL5 or RPL11 genotype or without gene identification
3. Severe infection or any other uncontrolled severe condition.
4. Uncontrolled hypertension
5. Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months.
6. Use of investigational agents within 30 days or any anticancer therapy (including IMiD) within 2 weeks before the study entry. The patient must have recovered at least a grade 1 from all acute toxicity from any previous therapy.
7. Use of EPO within 4 weeks of study entry
8. Active cancer or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast.
9. Patient already enrolled in another therapeutic trial of an investigational drug.
10. Known HIV infection or active hepatitis B or C.
11. Women who are or could become pregnant or who are currently breastfeeding.
12. Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form.
13. Patient eligible at short or medium term for allogeneic stem cell transplantation.
14. Known allergies to luspatercept or any of its excipients
15. No affiliation to a health insurance system
16. For men and women of reproductive potential: unwillingness to be abstinent or use double anticonception during the trial period.
17. Persons deprived of liberty by judicial or administrative decision
18. Persons subject to a legal protection measure (guardianship, curatorship, safeguard of justice)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. the proportion of patients who achieve an erythroid response, defined as a reduction in the transfusion burden of at least 33% from baseline (the 12-week period before the first dose of luspatercept) during 12 weeks plus a reduction of at least 2 red cell units over this 12-week interval.
2. The proportion of patients with a mean hemoglobin concentration increase of 1.0 g/dL or higher from baseline over a continuous 12-week interval in the absence of red blood cell transfusions

Secondary endpoints 5

1. Proportion of patients with a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval,
2. Proportion of patients with a reduction in the transfusion burden of at least 50% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval,
3. Proportion of patients with a reduction in the transfusion burden of at least 33% from baseline during weeks 37 through 48 plus a reduction of at least 2 red-cell units over this 12-week interval
4. Proportion of patients with a reduction in the transfusion burden of at least 50% from baseline during weeks 37 through 48 plus a reduction of at least 2 red-cell units over this 12-week interval
5. Mean change from baseline in the transfusion burden during weeks 13 through 24 and during weeks 37 through 48

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eurobloodnet Association

Sponsor organisation

Eurobloodnet Association

Address

1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Eurobloodnet Association

Contact name

Thierry LEBLANC

Public contact point

Organisation

Eurobloodnet Association

Contact name

Fatiha CHERMAT

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications