A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Oral Rilzabrutinib (PRN1008) in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Oral Rilzabrutinib (PRN1008) in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)
This was a randomized, double-blind study of rilzabrutinib in patients with persistent or chronic ITP, with an average platelet count of <30,000/μL (and no single platelet count >35,000/μL) on two counts at least 5 days apart in the 14 days before treatment begins. Patients received rilzabrutinib or placebo 400mg twice daily.
For each patient, the study lasted up to 60 weeks from the start of the Screening Period to the End of Study (EOS) visit. This included Screening (up to 4 weeks) through a 12 to 24-week Blinded Treatment Period followed by a 28-week Open-Label Period. Followed by a 4-week post dose follow-up.
For adult participants, the maximum duration of the long-term extension (LTE) period was 12 months from the date of the last adult participant to enter the LTE.
For pediatric participants, the maximum duration of the LTE period was 12 months from the date of the last pediatric participant to enter the LTE.
Inclusion Criteria:
Male and female with primary ITP with duration of >6 months in pediatric participants aged 12 to <18 years (pediatric participants aged 10 to <12 years will be enrolled in the EU [EEA countries] only) and duration of >3 months in ages 18 years and above
Patients who had a response (achievement of platelet count ≥50,000/µL) to IVIg/anti-D or CSs that was not sustained and who have documented intolerance, insufficient response or any contra-indication to any appropriate courses of standard of care ITP therapy
An average of 2 platelet counts at least 5 days apart of <30,000/µL during the Screening period and no single platelet count >35,000/µL, within 14 days prior to the first dose of study drug.
- Pediatric patients must additionally be determined to need treatment for ITP as per clinical assessment by the Investigator.
Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.5 X 10^9/L, AST/ALT ≤1.5 x upper limit of normal [ULN], albumin ≥3 g/dL, total bilirubin ≤1.5 x ULN [unless the patient has documented Gilbert syndrome], glomerular filtration rate >50 [Cockcroft and Gault method for adult and Bedside Schwartz Equation for Pediatric participants])
Hemoglobin >9 g/dL within 1 week prior to Study Day 1
All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Patients must be able to provide written informed consent or informed assent with corresponding informed consent obtained from the patient's guardian and agree to the schedule of assessments
Exclusion Criteria:
Patients with secondary ITP
Pregnant or lactating women
History (within 5 years of Study Day 1) or current, active malignancy requiring or likely to require chemotherapeutic or surgical treatment during the study, with the exception of non melanoma skin cancer
Transfusion with blood, blood products, plasmapheresis, or use of any other rescue medications with intent to increase platelet count within 14 days before Study Day 1
Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses)
Immunosuppressant drugs other than CSs within 5 times the elimination half-life of the drug or 14 days of Study Day 1, whichever is longer
Treatment with rituximab or splenectomy within the 3 months prior to Study Day 1
- Patients treated with rituximab will have normal B-cell counts prior to enrollment
Had received any investigational drug within the 30 days before receiving the first dose of study medication, or at least 5 times elimination half-life of the drug (whichever is longer); patient should not be using an investigational device at the time of dosing
History of solid organ transplant
Myelodysplastic syndrome
Live vaccine within 28 days prior to Study Day 1 or plan to receive one during the study
Planned surgery in the time frame of the dosing period
Los Angeles, California 90033, United States
San Francisco, California 94158, United States
Torrance, California 90502, United States
Whittier, California 90602, United States
Centennial, Colorado 80112, United States
Weeki Wachee, Florida 34607, United States
Atlanta, Georgia 30322, United States
Chicago, Illinois 60612, United States
Louisville, Kentucky 40202, United States
Cleveland, Ohio 44106, United States
Philadelphia, Pennsylvania 19104, United States
Salt Lake City, Utah 84112, United States
Capital Federal, Buenos Aires C1280AEB, Argentina
Salvador, Estado de Bahia 41253190, Brazil
Cascavel, Paraná 85806-300, Brazil
Porto Alegre, Rio Grande do Sul 90035 003, Brazil
Rio de Janeiro, 20211030, Brazil
Wuhan, Hubei 430022, China
Shenyang, Liaoning 110022, China
Xi'an, Shaanxi 710068, China
Jinan, Shandong 250012, China
Tianjin, Tianjin Municipality 300020, China
Kunming, Yunnan 650101, China
Tsuchiura-shi, Ibaraki, Japan
Sagamihara-shi, Kanagawa 252-0375, Japan
Suita-shi, Osaka 565-0871, Japan
Iruma-gun, Saitama 350-0495, Japan
Bunkyo-ku, Tokyo 113-8655, Japan
Meguro-ku, Tokyo 152-8902, Japan
Sumida-ku, Tokyo 130-8575, Japan
Saitama-shi, 330-8777, Japan
Delegacion Benito Juarez, 03720, Mexico
Norfolk, NR31 6LA, United Kingdom