Improvement of MRI assessed cerebral Perfusion and oxygenation by luspatercept-induced Anemia Correction in non-transfusion dependent Thalassemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

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

14 Jul 2024 → ongoing

Decision date (initial)

2023-11-17

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Amsterdam UMC, Medical centers

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess whether luspatercept can improve the cerebral oxygen metabolism (CMRO2) in patients with non-transfusion-dependent thalassemia (NTDT) with Hb increase of ≥ 1 g/dL

Secondary objectives 4

1. To assess the effect of luspatercept treatment on CMRO2 in NTDT patients
2. To assess the effect of luspatercept treatment on cerebral blood flow (CBF) in patients with NTDT
3. To assess the effect of luspatercept treatment on processing speed as measure of neurocognitive impairment
4. To assess the effect of luspatercept treatment on cardiac parameters of pulmonary hypertension (NTproBNP and TRV)

Conditions and MedDRA coding

Non-transfusion dependent beta-thalassmia

Study design 1 period

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. NTDT beta-thalassemia
2. Baseline Hb level of ≤ 10.0 based on the mean Hb level 24 weeks before initiation of luspatercept g/dL
3. ≥ 18 years of age
4. ≤ 5 RBC units transfused in the 24 weeks prior to inclusion in the study
5. Participants, who if female and of childbearing potential, are using highly effective methods of contraception from study start to 30 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 30 days after the last dose of study drug.
6. Participant has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each participant; the participant’s legal representative or legal guardian, and the participant’s assent must be obtained).

Exclusion criteria 9

1. No informed consent has been given.
2. Contra-indication for MRI or acetazolamide
3. Female who is breast feeding or pregnant.
4. Hepatic dysfunction characterized by alanine aminotransferase (ALT) > 4 × ULN.
5. Severe renal dysfunction (estimated glomerular filtration rate <30mL/min).
6. History of malignancy within the past 2 years prior to participation requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy).
7. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent, including but not limited to the following: 1. Unstable angina pectoris or myocardial infarction or elective coronary intervention. 2. Congestive heart failure requiring hospitalization. 3. Uncontrolled clinically significant arrhythmias.
8. Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).
9. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cerebral metabolic rate of oxygen (CMRO2) is measured by MRI technique by T2 relaxation under spin tagging (TRUST).

Secondary endpoints 3

1. CBF will be measured by time-encoded CASL.
2. Transthoracic echocardiography will be performed in order to assess the TRV. These assessments will be performed at baseline, and 27 weeks later. If transthoracic echocardiography to assess the TRV has been performed within one year before the first study visit (prior to inclusion of the patient in the study), that previously performed transthoracic echocardiography will be used as baseline transthoracic echocardiography for this study.
3. General laboratory analysis will be performed on venous blood samples at baseline, every three weeks after start of treatment until week 27. Analysis consists of hemoglobin, leukocyte and platelet count, renal and liver assessments and NT-proBNP.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

Meibergdreef 9

City

Amsterdam

Postcode

1105 AZ

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

Prof. dr. B.J. Biemond

Public contact point

Organisation

Amsterdam UMC

Contact name

Prof. dr. B.J. Biemond

Locations

1 EU/EEA country · 2 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 7 files

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

Application history

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