A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials

Beta-thalassemia Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04064060
• Other study ID #: ACE-536-LTFU-001
• Secondary ID: U1111-1235-81232
• Status: Recruiting
• Phase: Phase 3
• Start date: August 12, 2019
• Est. completion date: May 12, 2028

Study information

• Verified date: May 2024
• Source: Celgene
• Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following participants:

• Participants receiving luspatercept on a parent protocol at the time of their transition to the rollover study, who tolerate the protocol-prescribed regimen in the parent trial and, in the opinion of the investigator, may derive clinical benefit from continuing treatment with luspatercept

• Participants in the follow-up phase previously treated with luspatercept or placebo in the parent protocol will continue into long-term post-treatment follow-up in the rollover study until the follow-up commitments are met

• The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Participants will enter transition phase and depending on their background will enter either the treatment phase or the Long-term Post-treatment Follow-up (LTPTFU) phase

• Transition Phase is defined as one Enrollment visit

• Treatment Phase: For participants in luspatercept treatment the dose and schedule of luspatercept in this study will be the same as the last dose and schedule in the parent luspatercept study. This does not apply to participants that are in long-term follow-up from the parent protocol

• Follow-up Phase includes:

• 42 Day Safety Follow-up Visit

• During the Safety Follow up, the participants will be followed for 42 days after the last dose of luspatercept, for the assessment of safety-related parameters and adverse event (AE) reporting

• Long-term Post-treatment Follow-up (LTPTFU) Phase

• Participants will be followed for overall survival every 6 months for at least 5 years from first dose of luspatercept in the parent protocol, or 3 years of post-treatment from last dose, whichever occurs later, or until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Participants will also be monitored for progression to AML or any malignancies/pre-malignancies. New anticancer or disease related therapies should be collected at the same time schedule

Participants transitioning from a parent luspatercept study in post-treatment follow-up (safety or LTPTFU) will continue from the same equivalent point in this rollover study.

The rollover study will be terminated, and relevant participants will discontinue from the study when all participants fulfill at least 5 years from the first dose of luspatercept in the parent protocol, or 3 years of post-treatment from last dose, whichever occurs later.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 665
• Est. completion date: May 12, 2028
• Est. primary completion date: May 12, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Beta-thalassemia
• Myelodysplastic Syndromes
• Myelodysplastic Syndromes (MDS)
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
• Preleukemia
• Primary Myelofibrosis
• Thalassemia

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Australia	Local Institution - 103	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Local Institution - 102	Clayton	Victoria
Australia	Local Institution - 100	South Brisbane	Queensland
Belgium	Local Institution - 182	Brasschaat
Belgium	Local Institution - 180	Brugge
Belgium	Local Institution - 183	Ghent
Belgium	Local Institution - 184	Leuven
Bulgaria	Local Institution - 220	Boulevard	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment Sveti Georgi EAD	Plovdiv
Canada	Local Institution - 262	Toronto	Ontario
Canada	Local Institution - 263	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
China	Local Institution - 131	Beijing	Beijing
China	Local Institution - 134	Chengdu	Sichuan
China	Local Institution - 135	Guangzhou	Guangdong
China	Local Institution - 133	Hangzhou	Zhejiang
China	Local Institution - 132	Shanghai	Shanghai
China	Local Institution - 130	Tianjin	Tianjin
France	Local Institution - 305	Angers
France	Local Institution - 300	Creteil
France	Local Institution - 310	La Tronche
France	CHRU de Lille-Hopital Claude Huriez	Lille
France	Local Institution - 301	Marseille Cedex 9
France	Local Institution - 302	Paris
France	Local Institution - 307	Pessac Cedex
France	Local Institution - 304	Pierre Benite cedex
France	Local Institution - 308	Strasbourg
France	Local Institution - 309	Toulouse Cedex 9
France	Local Institution - 303	Tours
Germany	Local Institution - 341	Berlin
Germany	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Local Institution - 346	Dusseldorf
Germany	Local Institution - 343	Halle
Germany	Local Institution - 342	Hamburg
Germany	Local Institution - 344	Hannover
Germany	Local Institution - 349	Leipzig
Germany	Local Institution - 340	Mainz
Germany	Klinikum Rechts der Isar der Technischen Universitaet Muenchen	München
Greece	Aghia Sophia' Children's General Hospital of Athens	Athens
Greece	Laiko General Hospital of Athens - Center of Thalassemia	Athens
Greece	Local Institution - 384	Athens
Greece	Local Institution - 383	Rio Patras
Greece	General Hospital of Thessaloniki Hippokration	Thessaloniki
Israel	Local Institution - 425	Afula
Israel	Local Institution - 420	Haifa
Israel	Local Institution - 422	Jerusalem
Israel	Local Institution - 424	Jerusalem
Israel	Local Institution - 421	Nahariya
Israel	Local Institution - 423	Petah Tikva
Italy	Local Institution - 470	Allessandria
Italy	Local Institution - 464	Bologna
Italy	Local Institution - 466	Brindisi
Italy	Azienda Sanitaria Locale (ASL) Cagliari - Ospedale Regionale per le Microcitemie	Cagliari
Italy	Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna	Ferrara
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze	Toscana
Italy	Local Institution - 471	Firenze	Toscana
Italy	Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite	Genoa
Italy	Local Institution - 473	Lecce
Italy	Maggiore Polyclinic Hospital, IRCCS Ca' Granda	Milano
Italy	Local Institution - 479	Modena
Italy	AORN A Cardarelli	Napoli
Italy	AOU dell'Università degli Studi della Campania Luigi Vanvitelli	Napoli
Italy	Azienda Ospedaliero Universitaria S. Luigi Gonzaga	Orbassano
Italy	Irccs Policlinico San Matteo	Pavia
Italy	Azienda Ospedaliera Bianchi Melacrino Morelli	Reggio Di Calabria
Italy	Local Institution - 465	Roma
Italy	Local Institution - 474	Rozzano
Italy	Ospedale di Circolo di Varese	Varese
Italy	Local Institution - 463	Verona
Japan	Local Institution - 612	Chiba
Japan	Local Institution - 614	Himeji	Hyogo
Japan	Local Institution - 605	Hitachi	Ibaraki
Japan	Local Institution - 613	Kamakura
Japan	Local Institution - 601	Kamogawa	Chiba
Japan	Local Institution - 606	Matsuyama	Ehime
Japan	Local Institution - 611	Nagasaki-shi	Nagasaki
Japan	Local Institution - 610	Nagoya	Aichi
Japan	Ogaki Municipal Hospital	Ogaki	Gifu
Japan	Local Institution - 604	Osaka
Japan	Local Institution - 609	Osaka
Japan	Local Institution - 603	Sagamihara	Kanagawa
Japan	Local Institution - 0979	Sendai	Miyagi
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Local Institution - 602	Shibuya City	Tokyo
Japan	Local Institution - 600	Shinagawa City	Tokyo
Lebanon	Chronic Care Center	Hazmieh
Malaysia	Hospital Sultanah Bahiyah	Alor Setar	Kedah
Malaysia	Local Institution - 546	Ipoh	Perak
Malaysia	Hospital Sultanah Aminah	Johor Bahru	Johor
Malaysia	Queen Elizabeth Hospital	Kota Kinabalu	Sabah
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur
Malaysia	Hospital Umum Sarawak	Kuching	Sarawak
Netherlands	Local Institution - 580	Amsterdam
Spain	Local Institution - 681	Barakaldo
Spain	Local Institution - 685	Barcelona
Spain	Local Institution - 686	Barcelona
Spain	Local Institution - 687	Madrid
Spain	Local Institution - 682	Oviedo
Spain	Local Institution - 684	Salamanca
Spain	Local Institution - 680	Seville
Spain	Local Institution - 683	Valencia
Sweden	Local Institution - 720	Goteborg
Sweden	Local Institution - 722	Lund
Sweden	Local Institution - 721	Stockholm
Taiwan	Local Institution - 760	Kaohsiung, San Ming Dist.
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Siriraj Hospital Mahidol University	Bangkok
Thailand	Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital	Chiang Mai
Tunisia	Local Institution - 840	Sousse
Tunisia	Bone Marrow Transplant Center	Tunis
Tunisia	Local Institution - 842	Tunis
Tunisia	Military Hospital of Tunis	Tunis
Turkey	Acibadem Adana Hospital	Adana
Turkey	Local Institution - 885	Ankara
Turkey	Local Institution - 882	Istanbul
Turkey	Local Institution - 884	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Izmir
Turkey	Local Institution - 883	Mersin
United Kingdom	Local Institution - 925	Aberdeen
United Kingdom	Local Institution - 921	Leeds
United Kingdom	Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital	London
United Kingdom	Kings College Hospital	London
United Kingdom	Local Institution - 920	London
United Kingdom	Local Institution - 922	London
United Kingdom	Local Institution - 923	London
United Kingdom	Local Institution - 929	Oxford
United Kingdom	Local Institution - 926	Sutton in Ashfield
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Local Institution - 967	Cleveland	Ohio
United States	Local Institution - 961	Detroit	Michigan
United States	The University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Childrens Hospital Los Angeles RHU	Los Angeles	California
United States	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee
United States	Local Institution - 969	New York	New York
United States	Local Institution - 971	Oakland	California
United States	Local Institution - 972	Philadelphia	Pennsylvania
United States	Local Institution - 978	Stanford	California
United States	Local Institution - 975	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Canada,  China,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Lebanon,  Malaysia,  Netherlands,  Spain,  Sweden,  Taiwan,  Thailand,  Tunisia,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events (AEs)	Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept	From enrollment until at least 42 Day Safety Follow-up Phase or EOS (Approximately 5 years).
Primary	Number of participants progressing to high/very high risk MDS or AML.	Progression to high/very high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only).	Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary	Percentage of participants progressing to high/very high risk MDS or AML	Progression to high/very high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only)	Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary	Number of participants developing other malignancies/pre-malignancies	Development of other malignancies/pre-malignancies	Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary	Percentage of participants developing other malignancies/pre-malignancies	Development of other malignancies/pre-malignancies	Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary	Overall Survival	Time from date of randomization until death from any cause	Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary	Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses		Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary	Percentage of participants developing treatment emergent EMH masses		Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

External Links

•   BMS Clinical Trial Information