2022-502499-22-00
Recruiting
Phase 2
A Phase 2a Study to Evaluate the Safety and Pharmacokinetics of Luspatercept (ACE-536) in Pediatric Participants with Beta (β) Thalassemia.
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Celgene Corp.
- Enrollment
- 57
- Locations
- 7
- Primary Endpoint
- To determine the recommended dose (RD) for TD and NTD β-thalassemia participants
Overview
Brief Summary
To determine the recommended dose (RD) of luspatercept that is safe and tolerable in pediatric participants with transfusion-dependent (TD) or non-transfusion-dependent (NTD) β-thalassemia. To evaluate the pharmacokinetics (PK) of luspatercept in pediatric participants with TD or NTD β-thalassemia.
Eligibility Criteria
- Ages
- 0 years to 17 years (0-17 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Participants must satisfy the following criteria to be enrolled into the study: 1) Participant must be 6 years to < 18 years of age the time of signing the informed consent form (ICF)/informed assent form (IAF).
- •Participant (and when applicable, parent/legal representative) must understand and voluntarily sign an ICF/IAF prior to conducting any study-related assessments/procedures.
- •Participant (and when applicable, parent/legal representative) is willing and able to adhere to the study visit schedule and other protocol requirements.
- •Participant must have documented diagnosis of β-thalassemia or HbE/β-thalassemia.
- •Transfusion dependence: a) TD participant i) Participant is regularly transfused, defined as: ≥ 4 RBC transfusion events in the 24 weeks prior to enrollment with no transfusion-free period ≥ 42 days during that period. Note: For the purpose of the study, transfusions administered over 2 or 3 consecutive days are considered as part of a single transfusion event. Participant must have a history of regular transfusions for at least 2 years. b) NTD participant (ex-US sites only) i) Participant must have received < 4 RBC transfusion events in the 24 weeks prior to enrollment. ii) Participant must not be on a regular transfusion program and must be RBC transfusion-free for at least 8 weeks prior to enrollment. iii) Participant must have mean baseline hemoglobin ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to enrollment; hemoglobin values within 21 days post-transfusion will be excluded.
- •Participant has Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening
- •Female children of childbearing potential (FCCBP), individuals of childbearing potential (IOCBP), and male (as assigned at birth) participants that have reached puberty (and when applicable, parent/legal representative) must agree to undergo physician-approved reproductive education and discuss the side effects of the study therapy on reproduction.
- •Female children of childbearing potential, defined as females who have achieved menarche and/or breast development in Tanner Stage 2 or greater and have not undergone a hysterectomy or bilateral oophorectomy and IOCBP defined as a sexually mature woman who has achieved menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) must meet the following conditions below (Note: Secondary amenorrhea from any cause does not rule out childbearing potential): · Medically supervised serum pregnancy tests with a sensitivity of at least 25 mIU/mL must be conducted in FCCBP/IOCBP, including those who commit to complete abstinence*. Female children of childbearing potential/IOCBP must have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy (one of these tests should be performed by central laboratory). Female children of childbearing potential/IOCBP must agree to ongoing pregnancy testing during the course of the study at the EOT visit and at the 9-week Safety Follow-up visit. · Female participants must, as appropriate to age and at the discretion of the site Investigator, either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective** contraception without interruption, 28 days prior to starting IP, during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal t1/2 of luspatercept based on multiple-dose PK data) after discontinuation of study therapy.
- •Male (as assigned at birth) participants, as appropriate to age and the discretion of the study physician: · Must practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a synthetic or latex condom during sexual contact with a pregnant female or a FCCBP/IOCBP while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal t1/2 of luspatercept based on multiple-dose PK data) following IP discontinuation, even if he has undergone a successful vasectomy.
Exclusion Criteria
- •Not applicable as per Protocol Amendment
- •Participant has a diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin H); βthalassemia combined with α-thalassemia is allowed
- •Participant has active hepatitis C (HCV) infection as demonstrated by a positive HCV-ribonucleic acid (RNA) test of sufficient sensitivity, or active infectious hepatitis B as demonstrated by the presence of hepatitis B surface antigen (HBsAG) and/or hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) positive, or known positive human immunodeficiency virus (HIV). Note: Participants receiving antiviral therapies should have 2 negative HCV-RNA tests 3 months apart before ICF/IAF signature, ie, one test at the end of the antiviral therapy and the second test 3 months following the first test.
- •Not applicable as per Protocol Amendment
- •Not applicable as per Protocol Amendment
- •Not applicable as per Protocol Amendment
- •Participant has deep vein thrombosis (DVT), stroke, or other thromboembolic event(s) (except clogged indwelling catheter) requiring medical intervention ≤ 24 weeks prior to enrollment.
- •Not applicable as per Protocol Amendment
- •Participant has history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the IP (refer to the IB).
- •Participant use of cytotoxic agents, immunosuppressants ≤ 28 days prior to enrollment (ie, antithymocite globulin [ATG] or cyclosporine).
Outcomes
Primary Outcomes
To determine the recommended dose (RD) for TD and NTD β-thalassemia participants
To determine the recommended dose (RD) for TD and NTD β-thalassemia participants
To evaluate the pharmacokinetics (PK) for TD and NTD β-thalassemia participants
To evaluate the pharmacokinetics (PK) for TD and NTD β-thalassemia participants
Secondary Outcomes
- • The safety for TD and NTD β-thalassemia participants including: Type,frequency, seriousness, and severity of AEs and relationship to luspatercept (per NCI CTCAE version 5.0)
- • The immunogenicity in TD andNTD β-thalassemiaparticipants
- • The mean change in RBC transfusion burden in TDβ-thalassemia participants
- • The mean change in hemoglobin levels in NTD β-thalassemia participants
- • The mean change in mean daily dose of iron chelation therapy (ICT) in TD and NTD β-thalassemia participants
- • The mean change in serum ferritin in TD andNTD β-thalassemia participants
Investigators
GSM-CT
Scientific
Celgene Corp.
Study Sites (7)
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