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Trial details
A Phase 3B, open-label, single-arm, rollover study to evaluate long-term safety in subjects who have participated in other luspatercept (ACE-536) clinical trials
Current status:
Approved
|
Date registered:
22/05/2024
Trial version(s)
History: 02/04/2019
History: 02/04/2019
Current: 02/04/2019
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Main Information
Primary registry identifying number
LBCTR2019100218
Protocol number
ACE-536-LTFU-001
MOH registration number
43106/2019
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
01/11/2019
Primary sponsor
Celgene Corporation
Primary sponsor: Country of origin
USA
Public title
A Phase 3B, open-label, single-arm, rollover study to evaluate long-term safety in subjects who have participated in other luspatercept (ACE-536) clinical trials
Acronym
Scientific title
A Phase 3B, open-label, single-arm, rollover study to evaluate long-term safety in subjects who have participated in other luspatercept (ACE-536) clinical trials
Acronym
Brief summary of the study: English
This is a Phase 3b, open-label, single-arm, rollover study for subjects who have participated in other luspatercept (ACE-536) clinical trials. The primary objective is to evaluate the long-term safety (including progression to acute myeloid leukemia (AML) and/or other malignancies/pre-malignancies) of luspatercept in subjects who have participated in other luspatercept clinical trials. Another objective is to follow subjects for overall survival.
Brief summary of the study: Arabic
.(ACE-536) دراسة مرحلة 3 ب ، الدراسة المفتوحة ذات الذراع الواحد ، والانتقال إلى الأشخاص الذين شاركوا في تجارب سريرية أخرى الهدف الأساسي هو تقييم السلامة طويلة الأجل (بما في ذلك التقدم إلى سرطان الدم النخاعي الحاد(AML) (و / أو الأورام الخبيثة الأخرى / ما قبل الأورام الخبيثة) من luspatercept في الموضوعات الذين شاركوا في التجارب السريرية luspatercept الأخرى. هدف آخر هو متابعة الموضوعات للبقاء على قيد الحياة بشكل عام
Health conditions/problem studied: Specify
Prior participation on a clinical trial of luspatercept (ACE-536) in protocols eligible for participation in this study ACE-536-LTFU-001 with the following medical conditions: - Myelodysplastic Syndrome (MDS) - Beta (β)-thalassemia (THAL) - Myelofibrosis (MF) In Lebanon, only patients with beta (β)-thalassemia (THAL) have participated in previuos clinical trial of luspatercept (ACE-536).
Interventions: Specify
Starting as soon as Day 1 of Dose 1 of the rollover protocol, and assessed by the investigator prior to every subsequent treatment dose, subjects may have the dose level increased in a stepwise manner: beyond the starting dose from last dose of luspatercept from the parent protocol up to the defined maximum treatment dose. beyond the starting dose of 1.0 mg/kg in case of subjects crossing over to luspatercept from placebo arm of the parent protocol up to the defined maximum treatment dose.
Key inclusion and exclusion criteria: Inclusion criteria
Subjects must meet ALL the following criteria to be enrolled in this study: 1. Subject is ≥ 18 years at the time of signing the informed consent form (ICF). 2. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. 3. Subject has been participating in a luspatercept trial and continues to fulfill all the requirements of the parent protocol and the subject has been either: a. Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR b. Assigned to placebo arm in the parent protocol (at the time of unblinding or in follow-up) and should cross over to luspatercept treatment, OR c. Assigned to the Follow-up Phase of the parent protocol, previously treated with luspatercept or placebo in the parent protocol who shall continue into Long-term Post-treatment Follow-up Phase in the rollover study until the follow-up commitments are met (unless requirements are met as per parent protocol to crossover to luspatercept treatment). 4. Subject understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted. 5. Subject demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements. 6. Applies to on treatment subjects only- females of childbearing potential (FCBP) defined as a sexually mature woman who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must: a. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact. b. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with highly effective, contraception without interruption, 35 days prior to starting investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy. 7. Applies to on treatment subjects only- Male subjects must: a. Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 84 days following investigational product discontinuation even if he has undergone a successful vasectomy.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
65
Key inclusion and exclusion criteria: Exclusion criteria
The presence of any of the following will exclude a subject from enrollment: 1. Applies to on treatment subjects only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol. 2. Subject has met one or more criteria for study treatment discontinuation as stipulated in the parent luspatercept protocol. 3. First luspatercept transition visit into rollover study > 21 days after end of study (EOS) visit (last dose/visit in case of no EOS visit) of the parent luspatercept study with the exception of those subjects already in the Post-treatment Follow up Phase from the parent study. Note-Subject with current dose delays from the parent protocol during the Transition Phase, will continue in the rollover protocol regardless of the delay. 4. Applies to on treatment subjects only- Pregnant or breastfeeding females. 5. Subject has any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that would prevent the subject from participating in the study. 6. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 7. Subject has any condition that confounds the ability to interpret data from the study.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Safety
Trial scope: Specify scope
Study design: Allocation
N/A: Single arm study
Study design: Masking
Open (masking not used)
Study design: Control
N/A
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Single
IMP has market authorization
No
Name of IMP
Luspatercept (ACE-536)
Type of IMP
Others
Type of IMP: Specify
Recombinant Fusion Protein
Pharmaceutical class
Luspatercept is a recombinant fusion protein consisting of a modified form of the extracellular domain (ECD) of the human activin receptor IIB (ActRIIB) linked to the human immunoglobulin G1 fragment crystallizable (IgG1 Fc) domain. Luspatercept is a homodimeric protein comprised of 2 disulfide-linked polypeptide chains, each with 335 amino acids. Each polypeptide chain contains 3 sites for N-linked glycosylation (total of 6N- linked glycosylation sites per molecule). Peptide mapping and oligosaccharide analysis of luspatercept confirms the presence of highly branched N-linked glycans, typical of a recombinant protein produced in Chinese hamster ovary cells.
Therapeutic indication
Myelodysplastic Syndrome (MDS); Beta (β)-thalassemia (THAL); Myelofibrosis (MF); Only patients with beta (β)-thalassemia (THAL) are applicable in Lebanon
Therapeutic benefit
Luspatercept acts as a ligand trap for Growth Differentiation Factor 11 (GDF11) and other TGF-β family ligands to suppress Smad2/3 signaling. In nonclinical experiments, luspatercept has been shown to bind with high affinity to some TGF-β ligands (eg, GDF11, GDF8, BMP6, and activin B) but substantially less, or not at all, to others (eg, BMP9 and activin A). The mechanism of action of luspatercept is independent from that of erythropoietin. While erythropoietin stimulates proliferation and differentiation of early erythroid progenitors, luspatercept promotes stimulation of the later, maturation phase of erythroblast differentiation and maturation in the bone marrow.
Biospecimen retention
None retained
Biospecimen description
Not applicable
Target sample size
742
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
19/02/2020
Date of study closure: Type
Anticipated
Date of study closure: Date
30/06/2027
Recruitment status
Recruiting
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement description
Patients' full identity will not be on any of the study documents or samples collected and kept by the sponsor for their studies. The partial date of birth will only be collected. Only a unique participant number for the study will link the data or samples to the patients. These data may contain your gender and race, as well as any medical and scientific data required by the study.
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Food and Drug Administration
IND 112562
Sources of Monetary or Material Support
Name
Celgene Corporation
Secondary Sponsors
Name
Not applicable
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Aziz
Zoghbi
MCT-CRO, Berytech Technology and Health, 5th Floor, Damascus Road, Beirut, Lebanon
Lebanon
009611612500
zog_az@mct-cro.com
Regional Manager
Scientific
Ali
Taher
Chronic Care Center, Hazmieh, Lebanon
Lebanon
009613755669
ataher@aub.edu.lb
PI
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Chronic Care Center
Dr. Ali Taher
Professor of Medicine, Hematology & Oncology
NA
American university of Beirut
Dr. Ali Taher
Professor of Medicine, Hematology & Oncology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Chronic Care Center
30/09/2019
Michele Abi saad
cccmas@chroniccare.org.lb
05 455 103
Countries of Recruitment
Name
Lebanon
Bulgaria
Greece
Italy
Thailand
United Kingdom
United States of America
Belgium
Malaysia
Turkey
Australia
France
Germany
Canada
Netherlands
Spain
Sweden
Tunisia
Taiwan
Health Conditions or Problems Studied
Condition
Code
Keyword
Thalassemia
Thalassaemia (D56)
Thalassemia
Interventions
Intervention
Description
Keyword
ACE-536
every 3 weeks (Q3W):1.0 mg/kg or same dose as last dose of parent protocol in case IP dose modifications occurred
Treatment Phase
Primary Outcomes
Name
Time points
Measure
Adverse events (AEs)
Enrollment to 42 days post last dose
Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept
Development of other malignancies/pre-malignancies
Enrollment to Long-term Post-treatment Follow-up
Number and percentage of subjects developing other malignancies/premalignancies
Progression to high/very high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only). Not applicable for Lebanon patient population consists of B-Thal patients only.
Number and percentage of subjects progressing to high/very high risk MDS or AML
Enrollment to LTPTFU
Key Secondary Outcomes
Name
Time points
Measure
Overall survival
Enrollment to Long-term Post-treatment Follow-up
Time from date of randomization until death from any cause
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial