A Study of Pirtobrutinib in Participants With Immune Thrombocytopenia

Official title

A Phase 1/2, Dose-finding Study Investigating the Safety and Efficacy of Pirtobrutinib in Adults With Immune Thrombocytopenia

Overview

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

• Drug Pirtobrutinib
  Administered orally
• Drug Placebo
  Administered orally

Primary outcome measures

• 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 [Time frame: Baseline Up to Week 4]
• Phase 1-Dose Limiting Toxicity (DLT) of Pirtobrutinib [Time frame: Baseline Up to Week 4]
• Phase 1-Number of Participants with Treatment-Related Adverse Events as Assessed by Vital Signs: Blood Pressure, Pulse Rate, and Body Temperature [Time frame: Baseline Up to Week 16]
• 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) [Time frame: Baseline Up to Week 16]
• Phase 1-Number of Participants with Treatment-Related Adverse Events as Assessed by Electrocardiograms (ECGs): ECG QT Interval [Time frame: Baseline Up to Week 16]
• Phase 2-Efficacy of Pirtobrutinib Versus Placebo [Time frame: Baseline Up to Week 24]

Secondary outcome measures (8)

• Phase 1-Preliminary Efficacy of Pirtobrutinib [Time frame: Day 1 Up to Week 12]
• Phase 1-Evaluate the Extent of Disease Control [Time frame: Day 1 Up to Week 12]
• Phase 1: Pharmacokinetics (PK) of Pirtobrutinib [Time frame: Baseline Up to Week 16]
• Phase 2-Assess Additional Efficacy of Pirtobrutinib Versus Placebo [Time frame: Week 14 Up to Week 24]
• Phase 2-Evaluate the Extent of Disease Control of Pirtobrutinib Versus Placebo [Time frame: Baseline Up to Week 24]
• Phase 2-Evalulate the Extent of Disease Control of Pirtobrutinib Versus Placebo [Time frame: Baseline Up to Week 24]
• Phase 2-Describe the Use of Rescue Medications of Pirtobrutinib Versus Placebo [Time frame: Baseline Up to Week 24]
• Phase 2-Describe the PK of Pirtobrutinib [Time frame: Week 16 Up to Week 40]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Double blind

Primary purpose

Basic science

Study locations

United States · 11 centers

• USC Norris Comprehensive Cancer Center — Los Angeles
• Stanford University — Stanford
• MedStar Georgetown University Hospital — Washington D.C.
• University of Miami Hospital and Clinics Sylvester Comprehensive Cancer Center — Miami
• Bleeding and Clotting Disorders Institute — Peoria
• Ochsner Clinic Foundation — New Orleans
• Mayo Clinic — Rochester
• Clinical Research Alliance — Westbury
• … and 3 more centers

Poland · 5 centers

• Pratia Onkologia Katowice — Katowice
• Pratia MCM Krakow — Krakow
• Aidport sp z o.o. — Skorzewo
• MICS Centrum Medyczne Torun — Torun
• Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu — Wroclaw

South Korea · 5 centers

• Pusan National University Hospital — Busan
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Asan Medical Center — Seoul
• The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul

United Kingdom · 5 centers

• Bristol Haematology and Oncology Centre — Bristol
• St James's University Hospital — Leeds
• Leicester Royal Infirmary — Leicester
• Royal London Hospital — London
• Hammersmith Hospital — London

China · 4 centers

• Nanfang Hospital of Southern Medical University — Guangzhou
• Qilu Hospital of Shandong University — Jinan
• Hematology Hospital of the Chinese Academy of Medical Sciences — Tianjin
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan

Italy · 4 centers

• Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS — Bologna
• Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico — Milan
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma
• Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI) — Trieste

Spain · 4 centers

• Hospital Clinic de Barcelona — Barcelona
• Hospital Universitario de Burgos — Burgos
• Hospital General Universitario Morales Meseguer — Murcia
• Clinica Universidad de Navarra — Pamplona

France · 3 centers

• Hôpital Henri Mondor — Créteil
• CHU Dijon - Hopital du Bocage — Dijon
• CHU Bordeaux - Hôpital Haut-Lévêque — Pessac

Norway · 3 centers

• Haukeland University Hospital — Bergen
• Sykehuset Ostfold, Kalnes — Grålum
• St. Olavs Hospital Hf, Universitetssykehuset i Trondheim — Trondheim

Denmark · 1 center

• OUH — Odense C

Identifiers

NCT: NCT06721013 · 27294 · J2N-MC-JZNZ

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗