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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04064060




Registration number
NCT04064060
Ethics application status
Date submitted
9/08/2019
Date registered
21/08/2019

Titles & IDs
Public title
A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
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
Secondary ID [1] 0 0
U1111-1235-8123
Secondary ID [2] 0 0
ACE-536-LTFU-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes (MDS) 0 0
Beta-thalassemia 0 0
Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Luspatercept

Experimental: ACE-536 - Luspatercept will be administered as a subcutaneous (SC) injection to participants by the study staff at the clinical site and administration will be documented in the subject's source record.


Treatment: Drugs: Luspatercept
Luspatercept (ACE-536), an erythroid maturation agent, is a recombinant fusion protein consisting of a modified form of the extracellular domain (ECD) of the human activin receptor type IIB (ActRIIB) linked to the human immunoglobin G 1 (IgG1) Fc domain. ActRIIB receptor and its ligands are members of the transforming growth factor-ß (TGF-ß) superfamily. Members of the TGF-ß superfamily ligands, through their binding to activin receptors, are involved in modulating the differentiation of late-stage erythrocyte precursors (normoblasts) in the bone marrow. Luspatercept for injection is formulated as a sterile, preservative-free, lyophilized cake/powder. Luspatercept for injection is available in 25 mg and 75 mg vials and when reconstituted with water for injection, each consists of 50 mg/mL luspatercept in a 10 mM citrate buffer-based solution

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events (AEs)
Timepoint [1] 0 0
From enrollment until at least 42 Day Safety Follow-up Phase or EOS (Approximately 5 years).
Primary outcome [2] 0 0
Number of participants progressing to high/very high risk MDS or AML.
Timepoint [2] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary outcome [3] 0 0
Percentage of participants progressing to high/very high risk MDS or AML
Timepoint [3] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary outcome [4] 0 0
Number of participants developing other malignancies/pre-malignancies
Timepoint [4] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary outcome [5] 0 0
Percentage of participants developing other malignancies/pre-malignancies
Timepoint [5] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary outcome [2] 0 0
Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses
Timepoint [2] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary outcome [3] 0 0
Percentage of participants developing treatment emergent EMH masses
Timepoint [3] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

Eligibility
Key inclusion criteria
Participants must meet all the following criteria to be enrolled in this study:

1. Participant is = 18 years at the time of signing the informed consent form (ICF).
2. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
3. Participant has been participating in a luspatercept trial and continues to fulfill all the requirements of the parent protocol and the participant has been either:

1. Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR
2. 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
3. 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. Participant understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
5. Participant demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
6. Applies to on treatment Participants 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 or amenorrhea due to other medical reasons 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:

1. 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 participant practices true abstinence* from heterosexual contact.
2. 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 participants only- Male participants 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The presence of any of the following will exclude a participant from enrollment:

1. Applies to on treatment participants only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.
2. Participant has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.
3. Applies to on treatment participants only- More than 26 days between last luspatercept dose in the parent protocol and first dose into ACE-536-LTFU-001 protocol unless dose delay or dose discontinuation criteria met.
4. Applies to on treatment participants only- Pregnant or breastfeeding females.
5. Participant 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. Participant 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. Participant has any condition that confounds the ability to interpret data from the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - 100 - South Brisbane
Recruitment hospital [2] 0 0
Local Institution - 103 - Adelaide
Recruitment hospital [3] 0 0
Local Institution - 102 - Clayton
Recruitment hospital [4] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Belgium
State/province [11] 0 0
Brasschaat
Country [12] 0 0
Belgium
State/province [12] 0 0
Brugge
Country [13] 0 0
Belgium
State/province [13] 0 0
Ghent
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Plovdiv
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
China
State/province [18] 0 0
Beijing
Country [19] 0 0
China
State/province [19] 0 0
Guangdong
Country [20] 0 0
China
State/province [20] 0 0
Shanghai
Country [21] 0 0
China
State/province [21] 0 0
Sichuan
Country [22] 0 0
China
State/province [22] 0 0
Tianjin
Country [23] 0 0
China
State/province [23] 0 0
Zhejiang
Country [24] 0 0
France
State/province [24] 0 0
Angers
Country [25] 0 0
France
State/province [25] 0 0
Creteil
Country [26] 0 0
France
State/province [26] 0 0
La Tronche
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
France
State/province [28] 0 0
Marseille Cedex 9
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Pessac Cedex
Country [31] 0 0
France
State/province [31] 0 0
Pierre Benite cedex
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg
Country [33] 0 0
France
State/province [33] 0 0
Toulouse Cedex 9
Country [34] 0 0
France
State/province [34] 0 0
Tours
Country [35] 0 0
Germany
State/province [35] 0 0
Berlin
Country [36] 0 0
Germany
State/province [36] 0 0
Dresden
Country [37] 0 0
Germany
State/province [37] 0 0
Duesseldorf
Country [38] 0 0
Germany
State/province [38] 0 0
Dusseldorf
Country [39] 0 0
Germany
State/province [39] 0 0
Halle
Country [40] 0 0
Germany
State/province [40] 0 0
Hamburg
Country [41] 0 0
Germany
State/province [41] 0 0
Hannover
Country [42] 0 0
Germany
State/province [42] 0 0
Leipzig
Country [43] 0 0
Germany
State/province [43] 0 0
Mainz
Country [44] 0 0
Germany
State/province [44] 0 0
München
Country [45] 0 0
Greece
State/province [45] 0 0
Athens
Country [46] 0 0
Greece
State/province [46] 0 0
Rio Patras
Country [47] 0 0
Greece
State/province [47] 0 0
Thessaloniki
Country [48] 0 0
Israel
State/province [48] 0 0
Afula
Country [49] 0 0
Israel
State/province [49] 0 0
Haifa
Country [50] 0 0
Israel
State/province [50] 0 0
Jerusalem
Country [51] 0 0
Israel
State/province [51] 0 0
Nahariya
Country [52] 0 0
Israel
State/province [52] 0 0
Petah Tikva
Country [53] 0 0
Italy
State/province [53] 0 0
Toscana
Country [54] 0 0
Italy
State/province [54] 0 0
Allessandria
Country [55] 0 0
Italy
State/province [55] 0 0
Bologna
Country [56] 0 0
Italy
State/province [56] 0 0
Brindisi
Country [57] 0 0
Italy
State/province [57] 0 0
Cagliari
Country [58] 0 0
Italy
State/province [58] 0 0
Ferrara
Country [59] 0 0
Italy
State/province [59] 0 0
Genoa
Country [60] 0 0
Italy
State/province [60] 0 0
Lecce
Country [61] 0 0
Italy
State/province [61] 0 0
Milano
Country [62] 0 0
Italy
State/province [62] 0 0
Modena
Country [63] 0 0
Italy
State/province [63] 0 0
Napoli
Country [64] 0 0
Italy
State/province [64] 0 0
Orbassano
Country [65] 0 0
Italy
State/province [65] 0 0
Pavia
Country [66] 0 0
Italy
State/province [66] 0 0
Reggio Di Calabria
Country [67] 0 0
Italy
State/province [67] 0 0
Roma
Country [68] 0 0
Italy
State/province [68] 0 0
Rozzano
Country [69] 0 0
Italy
State/province [69] 0 0
Varese
Country [70] 0 0
Italy
State/province [70] 0 0
Verona
Country [71] 0 0
Japan
State/province [71] 0 0
Aichi
Country [72] 0 0
Japan
State/province [72] 0 0
Chiba
Country [73] 0 0
Japan
State/province [73] 0 0
Ehime
Country [74] 0 0
Japan
State/province [74] 0 0
Gifu
Country [75] 0 0
Japan
State/province [75] 0 0
Hyogo
Country [76] 0 0
Japan
State/province [76] 0 0
Ibaraki
Country [77] 0 0
Japan
State/province [77] 0 0
Kanagawa
Country [78] 0 0
Japan
State/province [78] 0 0
Miyagi
Country [79] 0 0
Japan
State/province [79] 0 0
Nagasaki
Country [80] 0 0
Japan
State/province [80] 0 0
Tokyo
Country [81] 0 0
Japan
State/province [81] 0 0
Kamakura
Country [82] 0 0
Japan
State/province [82] 0 0
Osaka
Country [83] 0 0
Lebanon
State/province [83] 0 0
Hazmieh
Country [84] 0 0
Malaysia
State/province [84] 0 0
Johor
Country [85] 0 0
Malaysia
State/province [85] 0 0
Kedah
Country [86] 0 0
Malaysia
State/province [86] 0 0
Perak
Country [87] 0 0
Malaysia
State/province [87] 0 0
Sabah
Country [88] 0 0
Malaysia
State/province [88] 0 0
Sarawak
Country [89] 0 0
Malaysia
State/province [89] 0 0
Wilayah Persekutuan Kuala Lumpur
Country [90] 0 0
Netherlands
State/province [90] 0 0
Amsterdam
Country [91] 0 0
Spain
State/province [91] 0 0
Barakaldo
Country [92] 0 0
Spain
State/province [92] 0 0
Barcelona
Country [93] 0 0
Spain
State/province [93] 0 0
Madrid
Country [94] 0 0
Spain
State/province [94] 0 0
Oviedo
Country [95] 0 0
Spain
State/province [95] 0 0
Salamanca
Country [96] 0 0
Spain
State/province [96] 0 0
Seville
Country [97] 0 0
Spain
State/province [97] 0 0
Valencia
Country [98] 0 0
Sweden
State/province [98] 0 0
Goteborg
Country [99] 0 0
Sweden
State/province [99] 0 0
Lund
Country [100] 0 0
Sweden
State/province [100] 0 0
Stockholm
Country [101] 0 0
Taiwan
State/province [101] 0 0
Kaohsiung, San Ming Dist.
Country [102] 0 0
Taiwan
State/province [102] 0 0
Taichung
Country [103] 0 0
Taiwan
State/province [103] 0 0
Taipei
Country [104] 0 0
Thailand
State/province [104] 0 0
Bangkok
Country [105] 0 0
Thailand
State/province [105] 0 0
Chiang Mai
Country [106] 0 0
Tunisia
State/province [106] 0 0
Sousse
Country [107] 0 0
Tunisia
State/province [107] 0 0
Tunis
Country [108] 0 0
Turkey
State/province [108] 0 0
Adana
Country [109] 0 0
Turkey
State/province [109] 0 0
Ankara
Country [110] 0 0
Turkey
State/province [110] 0 0
Istanbul
Country [111] 0 0
Turkey
State/province [111] 0 0
Izmir
Country [112] 0 0
Turkey
State/province [112] 0 0
Mersin
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Aberdeen
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Leeds
Country [115] 0 0
United Kingdom
State/province [115] 0 0
London
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Oxford
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Sutton in Ashfield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BMS Study Connect Contact Center www.BMSStudyConnect.com
Address 0 0
Country 0 0
Phone 0 0
855-907-3286
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria.

Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosurecommitment.html

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
See Plan Description
Available to whom?
See Plan Description
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.