A phase 3B, open-label, single-arm, rollover study to evaluate long-term safety of Luspatercept in subjects who have participated in other Luspatercept (ACE-536) clinical trials.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

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

26 Jul 2019 → ongoing

Decision date (initial)

2024-02-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celgene Corporation

External identifiers

EU CT number

2022-502498-40-00

EudraCT number

2018-002915-93

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

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.

Secondary objectives 1

1. To follow subjects for overall survival. To evaluate treatment emergent EMH (extramedullary hematopoiesis) masses.

Conditions and MedDRA coding

myelodysplastic syndrome (MDS); beta (β)-thalassemia (THAL); myelofibrosis (MF)

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Paul-Ehrlich-Institut

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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. 2) Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
3. 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 Posttreatment Follow-up Phase in the rollover study until the follow-up commitments are met (unless requirements are met as per parent protocol to cross over to luspatercept treatment).
4. 4) Subject understands and voluntarily signs an informed consent document prior to any studyrelated assessments or procedures being conducted.
5. 5) Subject demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
6. 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 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: a) Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. A medically supervised serum pregnancy test (conducted locally) is to be obtained and verified negative in all female subjects of childbearing potential at enrollment (for details refer to Section 6.1.7). 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. 7) Applies to on treatment subjects only- Male subjects must: a) 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 7

1. 1) Applies to on treatment subjects only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.
2. 2) Subject has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.
3. 3) Applies to on treatment subjects 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. 4) Applies to on treatment subjects only- Pregnant or breastfeeding females. If breastfeeding, agree to stop breastfeeding prior to the participation in the study and not to resume breastfeeding during treatment with luspatercept and until 3 months after the last dose.
5. 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. 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. 7) Subject has any condition that confounds the ability to interpret data from the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Adverse events (AEs)
2. Progression to high/very high-risk myelodysplastic syndrome (MDS)
3. Progression to Acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only)
4. Development of other malignancies/premalignancies

Secondary endpoints 2

1. Overall survival
2. Treatment-emergent EMH masses

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 3

Locations

8 EU/EEA countries · 20 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 70 files

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

Application history

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