Principal Investigator: Yazan Abou-Ismail
Keywords: Thrombocytopenia , Hematology , Rilzabrutinib Department: Hematology
IRB Number: 00144000
Specialty: Hematology/BMT
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Katherine Termath
katherine.termath@hsc.utah.edu
801-213-4128

Brief Summary

Efficacy Objectives
Primary Efficacy Objective
• To demonstrate the efficacy of rilzabrutinib versus placebo in patients with
refractory/relapsed ITP, based on the proportion of adult patients able to achieve platelet
counts at or above 50,000/μL for at least 8 out of the last 12 weeks of the 24-week
blinded treatment period

Key Secondary Efficacy Objectives
• To evaluate the effect of rilzabrutinib versus placebo on the number of weeks with
platelet count ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and at least doubled
from baseline, over the 24-week blinded treatment period in the absence of rescue
therapy
• To evaluate the effect of rilzabrutinib versus placebo on the number of weeks with
platelet counts between ≥30,000/μL and <50,000/μL and at least doubled from baseline
over the 24-week blinded treatment period in the absence of rescue therapy
• To evaluate the effect of rilzabrutinib versus placebo on the time to first platelet count of
≥50,000/μL OR between ≥30,000/μL and <50,000/μL and at least doubled from baseline
• To evaluate the effect of rilzabrutinib versus placebo on the proportion of patients
requiring rescue therapy
• To evaluate the effect of rilzabrutinib versus placebo on the change from baseline in
ITP Bleeding Scale (IBLS) assessment.

Other Secondary Objectives

Safety Objectives
• To evaluate the safety and tolerability of rilzabrutinib in patients aged 12 to <18 years
and in adult patients (≥18 years) with refractory/relapsed ITP

PK Objectives
• To characterize the PK of rilzabrutinib in patients aged 12 to <18 and in adult patients
(≥18 years) with refractory/relapsed ITP

Quality of Life (QOL) Objectives
• To evaluate the effect of rilzabrutinib on the general and disease-specific QoL of adult
patients (≥18 years) with refractory/relapsed ITP
• To evaluate the effect of rilzabrutinib on disease-specific QoL in patients aged 12 to <18
with refractory/relapsed ITP

Exploratory Endpoints
• Proportion of patients able to achieve platelet counts ≥50,000/μL for 4 out of last 8 weeks of
the 24-week treatment period
• Percentage of weeks with platelet count ≥50,000/μL OR between ≥30,000/μL and
<50,000/μL and at least doubled from baseline over the 24-week blinded treatment period in
the absence of rescue therapy
• Proportion of participants with complete response (defined as platelet count ≥100,000/μL on
2 consecutive visits at least 5 days apart and no bleeding or rescue ITP therapy use on and
through these two visits.
• Proportion of participants with platelet count ≥50,000/μL on 2 consecutive visits at least
5 days apart and no rescue ITP therapy use on and through these two visits.
• Proportion of patients who have a platelet count that exceeds 250,000/μL or 450,000/μL (for
patients on TPO-RAs)
• Change from baseline on the Fatigue, Psychological, Fear, Social Activity, Women’s
Reproductive Health, Work, and Overall QOL domains of the ITP-PAQ in adult patients
(≥18 years)
• Change from baseline in QoL as measured by the Euroqol-5 Dimensions-5 Level (Euroqol-
5D-5L) in adult patients (≥18 years)
• Change from baseline in disease-related symptom severity as measured by the Patient Global
Impression of Severity (PGIS)
• Patient perception of disease-related symptom improvement as measured by Patient Global
Impression of Change Scale (PGIC)
• PK parameters as assessed by population pharmacokinetic analysis
• BTK occupancy
• Changes from baseline in TPO levels, T-lymphocytes/ B-lymphocytes/natural killers
(T/B/NK) counts, immunoglobulin (IgG, IgG1, IgG4, IgM, IgE) levels
• (Optional) Vaccine-specific IgG response during treatment
See Appendix 10 for country-specific requirements of endpoints.

Inclusion Criteria

1. Patients will be male and female with primary ITP with duration of >6 months in ages 12 to
<18 years if not permitted per the country-specific requirements, (see Appendix 10, Country-specific requirements) and duration of >3 months in ages 18 years and above

2. 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|

3. An average of 2 platelet counts at least 5 days apart of <30,000/μL (and no single platelet
count >35,000/μL) within 14 days prior to the first dose of study drug
• Patients from 12 to <18 years of age must additionally be determined to need treatment
for ITP as per clinical assessment by the Investigator.

4. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.5 X 109/L,
AST/ALT ≤1.5 x upper limit of normal (ULN) [unless the patient has documented Gilbert syndrome], albumin ≥3 g/dL, total bilirubin ≤1.5 x ULN, estimated glomerular filtration rate (GFR) >50 (Cockcroft and Gault method)

5. Hemoglobin >9 g/dL within 1 week prior to dosing on Study Day 1

6. All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
A) Male patients
Male participants are eligible to participate if they agree to the following during the intervention period and for at least 13 weeks after the last administration of study intervention:
• Refrain from donating or cryopreserving sperm
Plus either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
(abstinent on a long term and persistent basis) and agree to remain abstinent
OR
- Must agree to use contraception/barrier as detailed below
- A male condom; the participant should also be advised of the benefit for a female partner to use a highly effective method of contraception (as described in Appendix 13 Contraceptive and barrier guidance) of the protocol as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant
B) Female patients
A female participant is eligible to participate if she is not pregnant or breastfeeding, and
one of the following conditions applies:
• Is a woman of nonchildbearing potential (WONCBP) as defined in Appendix 13 of the
protocol.
OR
Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method
that is highly effective (with a failure rate of <1% per year), with low user dependency, as
described in Appendix 13
• of the protocol, during the study intervention period (to be effective before starting the
intervention) and for at least 4 weeks after the last administration of study intervention
and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of
reproduction during this period.
• A WOCBP must have a negative highly sensitive pregnancy test (serum) as required by
local regulations) within 3 days before the first administration of study intervention
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum
pregnancy test is required. In such cases, the participant must be excluded from
participation if the serum pregnancy result is positive.

7. Patients must be able to provide written informed consent or informed assent with
corresponding informed consent obtained from the patients’ guardian and agree to the
schedule of assessments.

Exclusion Criteria

1. Patients with secondary ITP

2. Pregnant or lactating women

3. Electrocardiogram (ECG) findings for patients:
o aged ≥12 and <16: QTcF >449 msec (males) or >457 msec (females)
o aged ≥16 and <18: QTcF >450 msec (males) or >460 msec (females)
o aged ≥18, of QTcF >450 msec (males) or >470 msec (females), poorly controlled atrial fibrillation (ie, symptomatic patients or a ventricular rate above 100 beats/min on ECG), or other clinically significant abnormalities

4. 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

5. 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

6. Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than
10% variation from current doses)

7. 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

8. Treatment with rituximab or splenectomy within the 3 months prior to Study Day 1
o Patients treated with rituximab will have normal B-cell counts prior to enrollment

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
Study Day 1)

10. Use of known strong-to-moderate inducers or inhibitors of CYP3A within 14 days or
5 half-lives (whichever is longer) of Study Day 1 and until the end of the active treatment
period

11. Planned or concomitant use of any anticoagulants and platelet aggregation inhibiting drugs
such as aspirin (except for low dose aspirin up to 100 mg per day), nonsteroidal
anti-inflammatory drugs , thienopyridines within 14 days of Study Day 1 and until the end
of the active treatment period

12. 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
o Patients who previously received treatment with BTK inhibitors (except
rilzabrutinib) within 30 days before the first dose of study drug are not eligible
o Patients who previously received rilzabrutinib at any time are not eligible

13. Current drug or alcohol abuse

14. Refractory nausea and vomiting, malabsorption, external biliary shunt, significant bowel
resection, or any other condition that would preclude adequate study drug absorption

15. History of solid organ transplant

16. Positive at Screening for HIV, hepatitis B virus (HBV) (surface and core antibodies
unrelated to vaccination), or hepatitis C virus (HCV) (anti-HCV antibody confirmed with
Hep C RNA)
o Patients who are HBV surface antigen (HBsAg) positive will not be eligible.
o Patients who are HBsAg negative and HBV core antigen antibody (HBcAb)
positive will be tested for HBV surface antibody (HBsAb) and HBV DNA. If
HBV DNA is negative and HBsAb titer is ≥100 IU/L, patients may be enrolled.
Monthly HBV DNA monitoring will be required while on treatment and for
6 months after the last dose of the study drug. Positive HBV DNA results will be
managed appropriately as per local standard of care.
o Patients who are HBcAb positive, HBsAg negative with HBsAb titer <100 IU/L
or negative, are not eligible.

17. Positive QuantiFERON®-TB Gold, or QuantiFERON®-TB Gold Plus (QFT Plus) at
Screening unless all of the following 3 conditions are true (see Appendix 10 country-specific requirements):
a) Chest X-ray does not show evidence suggestive of active tuberculosis (TB) disease
b) There are no clinical signs and symptoms of pulmonary and/or extra-pulmonary TB
disease
c) Documented receipt of one of the following prophylactic treatment regimens:
i. Oral daily Isoniazid for 6 months or
ii. Oral daily Rifampin for 4 months or
iii. Isoniazid and Rifapentine weekly for 3 months (3HP)
On a case by case basis, after discussion and approval by the Sponsor, a local TB test that
is negative and is considered equivalent to 1 of the above tests may be used for eligibility.
For example, if a QuantiFERON-TB Gold, or QuantiFERON-TB Gold Plus (QFT Plus)
is indeterminate for any reason and a local blood test or T-Spot® TB test is negative, the
patient may be enrolled using the local result upon approval of the Sponsor.

18. History of recurring (2 or more) serious infections requiring intravenous antibiotic, antivirals or antifungals therapy within the last 3 months before Study Day 1 or active serious or moderate infection ongoing on the day of randomization

19. Myelodysplastic syndrome

20. Live vaccine within 28 days prior to Study 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 or Sponsor’s medical monitor, would interfere with patient safety, study
evaluations, and/or study procedures

23. Positive COVID-19 molecular test (if COVID-19 testing required per local guidelines to be
determined for each site)

24. COVID-19 vaccine within 14 days prior to Study Day 1 or planned during the last 12 weeks
of blinded treatment period