Contributions
Abstract: PB1733
Type: Publication Only
Session title: Platelet disorders
Background
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated platelet destruction and impaired production, leading to thrombocytopenia, a predisposition to bleeding, and diminished quality of life. Although initial response rates to standard therapy are generally high, long-term tolerability and durable remission remain elusive. Rilzabrutinib is an oral, reversible Bruton tyrosine kinase (BTK) inhibitor targeting mechanisms driving ITP. Preclinical studies of rilzabrutinib showed simultaneous rapid anti-inflammatory effects, along with neutralization and prevention of autoantibody signaling. In an ongoing phase I/II study of rilzabrutinib (± concomitant ITP therapy), 400 mg BID was identified as the optimal dose in patients with relapsed or refractory ITP. Preliminary results showed rapid, durable platelet response increases with a well-tolerated safety profile.
Aims
LUNA3 is a multicenter, randomized phase III study with open-label extension evaluating the efficacy and safety of rilzabrutinib vs placebo in adult and adolescent patients with persistent or chronic ITP (CT.gov: NCT04562766; EudraCT: 2020-002063-60).
Methods
Eligible patients must have primary ITP for a duration of >6 mo for adolescents (ages 12-17 y) or >3 mo for adults (age ≥18 y) and an average of 2 platelet counts <30×109/L (no single count >35×109/L) within 2 wk prior to treatment. Eligible patients should have a previous response (platelet count ≥50×109/L) to intravenous immunoglobulin/anti-D or corticosteroids that was insufficient or not sustained, or documented intolerance or insufficient response to any appropriate courses of standard-of-care ITP therapy. Randomization is carried out separately for the 2 age groups (12-17 y and ≥18 y). Within the 2 age groups, patients are stratified by splenectomy status (yes/no) and thrombocytopenia severity (platelet counts <15×109/L or ≥15×109/L). Patients are randomized 2:1 to oral rilzabrutinib 400 mg BID or placebo to receive double-blind treatment for up to 24 wk, followed by open-label treatment for 28 wk, and then a 4-wk safety follow-up. After 12 wk of double-blind treatment, non-responders will be given the option to receive open-label rilzabrutinib or discontinue from the study. Concomitant stable doses (maintained for at least 2 wk prior to study day 1) of ITP medication (corticosteroids and/or thrombopoietin-receptor agonists) are permitted. Patients who receive rescue medication may continue study treatment. The primary endpoint is the achievement of platelet counts ≥50×109/L for ≥8 of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue medication. Secondary endpoints include safety, duration of and time to platelet responses, rescue therapy use, and changes from baseline in bleeding scores (per ITP-BAT assessment). Responders may enter an additional 12-mo long-term extension.
Results
This is a recently-initiated, global clinical trial with the goal of enrolling approximately 194 patients.
Conclusion
The LUNA3 multicenter, phase III pivotal study is designed to evaluate the efficacy and safety of oral rilzabrutinib (± concomitant ITP therapy) vs placebo in adults and adolescents with persistent or chronic ITP who had insufficient response or were intolerant to previous ITP therapy. These study results will provide further support for a unique treatment mechanism via BTK inhibition to target the underlying pathology of ITP.
Keyword(s): Immune therapy, Immune thrombocytopenia (ITP), Tyrosine kinase inhibitor
Abstract: PB1733
Type: Publication Only
Session title: Platelet disorders
Background
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated platelet destruction and impaired production, leading to thrombocytopenia, a predisposition to bleeding, and diminished quality of life. Although initial response rates to standard therapy are generally high, long-term tolerability and durable remission remain elusive. Rilzabrutinib is an oral, reversible Bruton tyrosine kinase (BTK) inhibitor targeting mechanisms driving ITP. Preclinical studies of rilzabrutinib showed simultaneous rapid anti-inflammatory effects, along with neutralization and prevention of autoantibody signaling. In an ongoing phase I/II study of rilzabrutinib (± concomitant ITP therapy), 400 mg BID was identified as the optimal dose in patients with relapsed or refractory ITP. Preliminary results showed rapid, durable platelet response increases with a well-tolerated safety profile.
Aims
LUNA3 is a multicenter, randomized phase III study with open-label extension evaluating the efficacy and safety of rilzabrutinib vs placebo in adult and adolescent patients with persistent or chronic ITP (CT.gov: NCT04562766; EudraCT: 2020-002063-60).
Methods
Eligible patients must have primary ITP for a duration of >6 mo for adolescents (ages 12-17 y) or >3 mo for adults (age ≥18 y) and an average of 2 platelet counts <30×109/L (no single count >35×109/L) within 2 wk prior to treatment. Eligible patients should have a previous response (platelet count ≥50×109/L) to intravenous immunoglobulin/anti-D or corticosteroids that was insufficient or not sustained, or documented intolerance or insufficient response to any appropriate courses of standard-of-care ITP therapy. Randomization is carried out separately for the 2 age groups (12-17 y and ≥18 y). Within the 2 age groups, patients are stratified by splenectomy status (yes/no) and thrombocytopenia severity (platelet counts <15×109/L or ≥15×109/L). Patients are randomized 2:1 to oral rilzabrutinib 400 mg BID or placebo to receive double-blind treatment for up to 24 wk, followed by open-label treatment for 28 wk, and then a 4-wk safety follow-up. After 12 wk of double-blind treatment, non-responders will be given the option to receive open-label rilzabrutinib or discontinue from the study. Concomitant stable doses (maintained for at least 2 wk prior to study day 1) of ITP medication (corticosteroids and/or thrombopoietin-receptor agonists) are permitted. Patients who receive rescue medication may continue study treatment. The primary endpoint is the achievement of platelet counts ≥50×109/L for ≥8 of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue medication. Secondary endpoints include safety, duration of and time to platelet responses, rescue therapy use, and changes from baseline in bleeding scores (per ITP-BAT assessment). Responders may enter an additional 12-mo long-term extension.
Results
This is a recently-initiated, global clinical trial with the goal of enrolling approximately 194 patients.
Conclusion
The LUNA3 multicenter, phase III pivotal study is designed to evaluate the efficacy and safety of oral rilzabrutinib (± concomitant ITP therapy) vs placebo in adults and adolescents with persistent or chronic ITP who had insufficient response or were intolerant to previous ITP therapy. These study results will provide further support for a unique treatment mechanism via BTK inhibition to target the underlying pathology of ITP.
Keyword(s): Immune therapy, Immune thrombocytopenia (ITP), Tyrosine kinase inhibitor