Study of Safety & PK of Luspatercept (ACE-536) in Pediatric Participants With Beta (β)-Thalassemia
ConditionBeta-Thalassemia
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age6-17
SponsorCelgene
About this trial
This is a Phase 2a study to evaluate the safety and pharmacokinetics (PK) of luspatercept in pediatric participants with β-thalassemia.
The study will be conducted in 2 parts for both transfusion-dependent (TD) and non-transfusion-dependent (NTD) β-thalassemia participants: TD Part A will be in adolescent participants aged 12 to \<18 years with two dose escalation cohorts, followed by a dose expansion cohorts. NTD Part A will be conducted in the same age group participants as TD Part A with dose confirmation and expansion cohorts. After Part A TD participants have completed at least one year of treatment, all available safety data from Part A adolescent participants will be evaluated before initiating TD and NTD Part B in the age group from 6 to \<12 years old. Part B will consist of two dose escalation cohorts for TD and two dose escalation cohorts for NTD.
Upon completion of the Treatment Period, participants of any cohort who are benefiting from the study treatment, will be offered the opportunity to continue luspatercept treatment in the Long-term Treatment Period for up to 5 years from their first dose.
Participants who discontinue study treatment at any time will continue in the Posttreatment Follow-up Period for at least 5 years from their first dose of luspatercept, or 3 years from their last dose, whichever occurs later, or until they withdraw consent/assent, are lost to follow-up, or the End of Trial, whichever occurs first. If neither commercial treatment nor an LTFU (long-term follow-up) protocol is available at that time, continued treatment will be provided within this study or via an alternative mechanism, at the Sponsor's discretion.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants must be 6 years to < 18 years of age at the time of signing the informed consent form (ICF)/informed assent form (IAF).
Participants (and when applicable, parent/legal representative) must understand and voluntarily sign an ICF/IAF prior to conducting any study-related assessments/procedures.
Participants (and when applicable, parent/legal representative) is willing and able to adhere to the study visit schedule and other protocol requirements.
Participants must have documented diagnosis of β-thalassemia or Hemoglobin E/β-thalassemia.
Disqualifiers
Participant has a diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin H); β-thalassemia combined with α-thalassemia is allowed.
Participant has of active hepatitis C (HCV) infection, as demonstrated by a positive HCF-ribonucleic acid (RNS) 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).
Participant has deep vein thrombosis (DVT), stroke, or other thromboembolic event(s) (except clogged indwelling catheter) requiring medical intervention ≤ 24 weeks prior to enrollment.
Participant has platelet count > 1000 x 109/L.
Trial design
Design model
Sequential
Treatments tested in this trial
ACE-536
DrugSpecified dose on specified days
Treatment groups
99 Participants
are divided into 9 treatment groups9
Treatment groupsSee each treatment group below.
Group A: Cohort 1: TD Dose Escalation Cohort: 12 to < 18 years Luspatercept 0.75 mg/kgExperimental treatment 1 intervention
Group B: Cohort 2: TD Dose Escalation Cohort: 12 to < 18 years: Luspatercept 1.0 mg/kgExperimental treatment 1 intervention
Group C: Cohort 3: TD Dose Expansion Cohort: 12 to <18 years Luspatercept 1.0 mg/kgExperimental treatment 1 intervention
Group D: Cohort 4: TD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kgExperimental treatment 1 intervention
Group E: Cohort 5: TD Dose Escalation Cohort: 6 to <12 years Luspatercept 1.2 mg/kgExperimental treatment 1 intervention
Group F: Cohort 6: NTD Dose Confirmation Cohort: 12 to < 18 years Luspatercept 1.0 mg/kgExperimental treatment 1 intervention
Group G: Cohort 7: NTD Dose Expansion Cohort: NTD 12 to < 18 yearsExperimental treatment 1 intervention
Group H: Cohort 8: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kgExperimental treatment 1 intervention
Group I: Cohort 9: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.2 mg/kgExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Determination of the Recommended Dose (RD
Determine the recommended dose of luspatercept that is safe and tolerable in pediatric participants with transfusion-dependent B-thalassemia or non-transfusion-dependent β-thalassemia
Time frame
Cycle 1 up to the day before Cycle 2 Day 1 or Study Day 22 if not receiving the second treatment cycle2
Pharmacokinetics - Cmax
Maximum serum concentration of drug
Time frame
Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year3
Pharmacokinetics - AUC
Area under the curve
Time frame
Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year4
Pharmacokinetics (PK) - t1/2
Half-life
Time frame
Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 yearSecondary outcomes
1
Mean change in Red Blood Cell (RBC) Transfusion Burden for transfusion-dependent β-thalassemia participants
Change from baseline as continuous variable
Time frame
12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years2
Mean change in hemoglobin levels for non-transfusion-dependent β-thalassemia participants
Change from baseline as continuous variable
Time frame
12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years3
Immunogenicity
Frequency of antidrug antibodies (ADA)
Time frame
Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year4
Mean change from baseline in mean daily dose of iron chelation therapy (ICT)
Change from baseline as continuous variable
Time frame
12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Celgene
Lead sponsor
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Collaborator
Source ClinicalTrials.gov