Immune Thrombocytopenia (ITP)
Conditions
Keywords
Primary ITP
Brief summary
The purpose of the phase 1 part of this study was to evaluate how well pirtobrutinib is tolerated and what side effects may occur. The phase 2 part of the study will further investigate efficacy and safety of multiple pirtobrutinib dosages versus placebo. The study drug will be administered orally in participants with Primary Immune Thrombocytopenia (ITP). Blood tests will be performed to check how much pirtobrutinib gets into the bloodstream and how long it takes the body to eliminate it. The study will last up to approximately 16 weeks for phase 1 dose-escalation and 28 weeks for phase 2 dose-optimization, excluding screening.
Interventions
DRUGPirtobrutinib
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase 1-Open label, Phase 2-Double-blind
Intervention model description
Phase 1-Open label Sequential, Phase 2-Double-blind Parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of primary ITP, defined as isolated thrombocytopenia not associated with another known disease process * Have documented history of response, defined as 2 or more platelet counts greater than or equal to 50,000/microliter (μL), to at least 1 prior line of therapy. Splenectomy is considered a line of therapy * Have relapsed or treatment-resistant primary ITP, with no available therapies known to provide clinical benefit * Have a platelet count less than 30,000/μL on 2 occasions at least 5 days apart in the 15 days before randomization * Have adequate liver, renal, and hematologic functions as defined by a table * Are willing to follow contraception requirements
Exclusion criteria
* Have a history of any thrombotic or embolic event within 12 months before screening * Had a transfusion with blood or blood products or plasmapheresis within 14 days (Phase 1) or within 28 days (Phase 2) of randomization * Have significant cardiovascular disease * Have a diagnosis or history of hematologic malignancy * Have hepatitis B virus (HBV) defined as positive for antigen of hepatitis B (HBsAg) or polymerase chain reaction (PCR) positive for HBV deoxyribonucleic acid (DNA) * Have hepatitis C virus (HCV) defined as positive for anti-HCV antibodies and PCR positive for HCV ribonucleic acid (RNA)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1-Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline Up to Week 4 | A summary of TEAEs and SAEs regardless of causality, will be reported in the Reported Adverse Events module |
| Phase 1-Dose Limiting Toxicity (DLT) of Pirtobrutinib | Baseline Up to Week 4 | DLTs of Pirtobrutinib |
| Phase 1-Number of Participants with Treatment-Related Adverse Events as Assessed by Vital Signs: Blood Pressure, Pulse Rate, and Body Temperature | Baseline Up to Week 16 | Blood Pressure, Pulse Rate, and Body Temperature |
| Phase 1-Number of Participants with Treatment-Related Adverse Events as Assessed by Clinical Lab Tests: Hematology, Clinical Chemistry, Urinalysis, Pregnancy, Hepatitis Serology and Cytomegalovirus (CMV) | Baseline Up to Week 16 | Hematology, Clinical Chemistry, Urinalysis, Pregnancy, Hepatitis Serology and Cytomegalovirus (CMV) |
| Phase 1-Number of Participants with Treatment-Related Adverse Events as Assessed by Electrocardiograms (ECGs): ECG QT Interval | Baseline Up to Week 16 | ECG QT Interval |
| Phase 2-Efficacy of Pirtobrutinib Versus Placebo | Baseline Up to Week 24 | Stable platelet response rate is defined as the proportion of participants achieving platelet count of greater than or equal to 50 thousand per microliter (k/μL) and on at least 4 of the 6 consecutive biweekly visits between weeks 14 and 24 in the absence of rescue therapy and prohibited concomitant medication that may impact efficacy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1-Preliminary Efficacy of Pirtobrutinib | Day 1 Up to Week 12 | Platelet response rate defined as proportion of participants who achieve at least 2 consecutive platelet counts of greater than or equal to 50 k/μL and an increase from baseline of greater than or equal to 20 k/μL to any time during treatment without the use of rescue medication within 4 weeks prior to the latest elevated platelet count. |
| Phase 1-Evaluate the Extent of Disease Control | Day 1 Up to Week 12 | Number of cumulative weeks with platelet counts greater than or equal to 50 k/μL by Week 12 |
| Phase 1: Pharmacokinetics (PK) of Pirtobrutinib | Baseline Up to Week 16 | PK: Plasma Concentrations of Pirtobrutinib |
| Phase 2-Assess Additional Efficacy of Pirtobrutinib Versus Placebo | Week 14 Up to Week 24 | Platelet response rate is defined as the proportion of participants with greater than or equal to 2 consecutive platelet counts greater than or equal to 50 k/μL and an increase of platelet count of greater than or equal to 20 k/μL from baseline to any time during treatment or follow-up without the use of rescue medication or prohibited concomitant medication that may impact efficacy within 4 weeks prior to the latest elevated platelet count |
| Phase 2-Evaluate the Extent of Disease Control of Pirtobrutinib Versus Placebo | Baseline Up to Week 24 | Number of cumulative weeks with platelet counts greater than or equal to 50 k/μL |
| Phase 2-Evalulate the Extent of Disease Control of Pirtobrutinib Versus Placebo | Baseline Up to Week 24 | Number of cumulative weeks with platelet counts greater than or equal to 100 k/μL |
| Phase 2-Describe the Use of Rescue Medications of Pirtobrutinib Versus Placebo | Baseline Up to Week 24 | Proportion of participants requiring rescue therapy |
| Phase 2-Describe the PK of Pirtobrutinib | Week 16 Up to Week 40 | PK: Plasma Concentrations of Pirtobrutinib |
Countries
China, Denmark, France, Italy, Norway, Poland, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed