An Adaptive, Open-Label, Dose-Finding, Phase 1/2 Study Investigating the Safety, Pharmacokinetics, and Clinical Activity of Rilzabrutinib (PRN1008), an Oral BTK Inhibitor, in Patients with Relapsed Immune Thrombocytopenia
- Conditions
- Immune Thrombocytopenic Purpura (ITP)low platelets10035534
- Registration Number
- NL-OMON52638
- Lead Sponsor
- Principia Biopharma, a Sanofi Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 6
Part A
Inclusion Criteria:
1. Male or female patients, aged 18 to 80 years old (Czech Republic and Norway
only: 18 to 65 years old)
2. Immune-related ITP (both primary and secondary)
3. Refractory or relapsed patients with no available and approved therapeutic
options
with a platelet count of <30,000/µL on two occasions no less than 7 days apart
in
the 15 days prior to beginning study treatment.
4. A history of response (two or more platelet counts >=50,000/µL with an
increase
of at least 20,000/µL) to at least one prior line of therapy (with splenectomy
being
considered a line of therapy)
5. Adequate hematologic, hepatic, and renal function (absolute neutrophil count
>=1.5 × 109/L, hemoglobin [Hgb] >9 g/dL, AST/ALT <=1.5 × ULN, albumin
>=3 g/dL, total bilirubin <=1.5 × ULN, estimated glomerular filtration rate [eGFR]
> 60 mL/min (Cockcroft and Gault method) (C1D1 pre-dose may be checked up to
Day -3 prior to C1D1)
6. Female patients who are of reproductive potential must agree for the
duration of
active treatment in the study to use a highly effective means of contraception
(hormonal contraception methods that inhibits ovulation, intrauterine device,
intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized
partner, or true abstinence; when this is in line with the preferred and usual
lifestyle of the patient). Unless surgically sterile, postmenopausal females
should
have menopause confirmed by follicle-stimulating hormone (FSH) testing.
7. Able to provide written informed consent and agreeable to the schedule of
assessments
Part B
Inclusion Criteria:
1. Male or female patients, aged 18 to 80 years old
2. Patients with immune-related ITP (both primary and secondary) as defined by
current guidelines with at least 3 months duration
3. Patients who had a response (achievement of platelet count >=50,000/µL) to
IVIg/anti-D or corticosteroid that was not sustained and failed at least one
other
ITP therapy (that was not IVIg or corticosteroid 4. Patients with a platelet
count of <30,000/µL on two occasions no less than 7 days
apart in the 15 days before treatment begins, and no platelet count above
35,000/µL on Study Day 1.
5. Patients with adequate hematologic, hepatic, and renal function (absolute
neutrophil count >=1.5 × 109/L, Hgb >9 g/dL, AST/ALT <=1.5 × ULN, albumin
>=3 g/dL, total bilirubin <=1.5 × ULN, eGFR >50 mL/min (Cockcroft and Gault
method) (pre-dose may be checked up to Day -3)
6. Female patients who are of reproductive potential must agree for the duration
of active treatment in the study to use a highly effective means of
contraception
(hormonal contraception methods that inhibits ovulation, intrauterine device,
intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized
partner, or true abstinence; when this is in line with the preferred and usual
lifestyle of the patient). Unless surgically sterile, postmenopausal females
should
have menopause confirmed by FSH testing.
7. Able to provide written informed consent and agreeable to the schedule of
assessments
Part A:
Exclusion Criteria:
1. Pregnant or lactating women
2. ECG findings of QTcF >450 msec (males) or >470 msec (females), poorly
controlled atrial fibrillation (i.e., symptomatic patients or a ventricular
rate above
100 beats/min on ECG), or other clinically significant abnormalities 3. History
of current, active malignancy requiring or likely to require
chemotherapeutic or surgical treatment during the trial, with the exception
of non-melanoma skin cancer
4. Transfusion with blood or blood products or plasmapheresis within 2 weeks
before
Day 1
5. Change in corticosteroid and/or TPO agonist dose within 2 weeks prior to Day
1
(more than 10% variation from Day 1 daily doses)
6. Use of rescue medications other than corticosteroids or TPO in Exclusion
Criterion
#5 in the two weeks before Day 1
7. Immunosuppressant drugs other than corticosteroids - these drugs should be
discontinued for at least 14 days before Day 1
8. Treatment with rituximab or splenectomy within the 3 months prior to Day 1
9. Ongoing need for the use of proton pump inhibitor drugs such as omeprazole
and esomeprazole (it is acceptable to change patient to H2 receptor blocking
drugs
prior to Day 1)
10. Concomitant use of known strong-to-moderate inducers or inhibitors of CYP3A
within 3 days or 5 half-lives (whichever is longer) of Day 1
11. Use of CYP3A-sensitive substrate drugs with a narrow therapeutic index
within
3 days or 5 half-lives (whichever is longer) of study drug dosing including,
but not
limited to, alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine,
ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or terfenadine
12. Planned or concomitant use of any anticoagulants and platelet aggregation
inhibiting drugs such as aspirin, non-steroidal anti-inflammatory drugs
(NSAIDs),
thienopyridenes (within 14 days of planned dosing through end of follow-up)
13. Has 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
14. Current drug or alcohol abuse
15. Refractory nausea and vomiting, malabsorption, external biliary shunt, or
significant bowel resection that would preclude adequate study drug absorption
16. History of solid organ transplant
17. Positive screening for human immunodeficiency virus (HIV), hepatitis B
(surface
antigen and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV
antibody confirmed with HCV RNA)
18. History of serious infections requiring intravenous therapy within the last
3 months
before Day 1
19. Clinically significant cognitive dysfunction (>= Grade 1) or medical history
suggestive of increased risk for cognitive dysfunction during the study
20. Live vaccine within 28 days prior to Day 1 or plan to receive one during
the study
21. Planned surgery in the time frame of the dosing period
22. Any other clinically significant disease, condition, or medical history
that, in the
opinion of the Investigator, would interfere with patient safety, study
evaluations,
and/or study procedures
Part B
1. Pregnant or lactating women
2. ECG findings of QTcF >450 msec (males) or >470 msec (femal
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method