A Clinical Trial to Test the Safety, Effect, and Activity of Rilzabrutinib (PRN1008) in Adult and Adolescent Patients with Persistent or Chronic Immune Thrombocytopenia (ITP).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Principia Biopharma Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

5 Feb 2021 → 15 May 2025

Decision date (initial)

2024-04-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-509401-71-00

EudraCT number

2020-002063-60

ClinicalTrials.gov

NCT04562766

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Therapy, Efficacy

To demonstrate the efficacy of rilzabrutinib versus placebo in patients with refractory/relapsed ITP, based on the durability of platelet response during the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy.

Secondary objectives 11

1. 6. (EU and UK) To evaluate the change from baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS).
2. 7. To evaluate the stability of platelet response of treatment rilzabrutinib.
3. 8. To evaluate the safety and tolerability of rilzabrutinib in pediatric participants (≥10 years - <18 years) and adult participants (≥18 years) with refractory/relapsed ITP.
4. 9. To characterize the PK of rilzabrutinib in pediatric participants (<18 years) and adult participants (≥18 years) with refractory/relapsed ITP.
5. 10. To evaluate the effect of rilzabrutinib on the general and disease-specific quality of life of adult patients (≥18 years) with refractory/relapsed ITP.
6. 11. To evaluate the effect of rilzabrutinib on disease-specific quality of life in in pediatric participants with refractory/relapsed ITP.
7. 1. 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
8. 2. To evaluate the effect of rilzabrutinib versus placebo on the number of weeks with platelet counts ≥30,000/μL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy
9. 3. 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
10. 4. To evaluate the effect of rilzabrutinib versus placebo on the proportion of patients requiring rescue therapy
11. 5. To evaluate the effect of rilzabrutinib versus placebo on the change from baseline on Item 10 of the ITP-PAQ (ie, physical fatigue) in adult participants (≥18 years) at Week 13

Conditions and MedDRA coding

Immune Thrombocytopenia (ITP)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002438-PIP02-19

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Patients will be 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.
2. 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. 3. 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.
4. 4. 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]).
5. 5. Hemoglobin >9 g/dL within 1 week prior to Study Day 1.
6. 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.
7. 7. 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 12

1. 1. Patients with secondary ITP.
2. 10. Myelodysplastic syndrome.
3. 11. Live vaccine within 28 days prior to Study Day 1 or plan to receive one during the study.
4. 2. Pregnant or lactating women.
5. 3. 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.
6. 4. 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.
7. 5. Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses).
8. 6. 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.
9. 7. 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.
10. 8. 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 - Patients who previously received treatment with Bruton’s Tyrosine Kinase (BTK) inhibitors (except rilzabrutinib) within 30 days before the first dose of study drug are not eligible - Patients who previously received rilzabrutinib at any time are not eligible.
11. 9. History of solid organ transplant.
12. 12. Planned surgery in the time frame of the dosing period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. (EU and UK) Proportion of adult participants 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 in the absence of rescue therapy.

Secondary endpoints 12

1. 1. 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.
2. 2. Number of weeks with platelet counts ≥30,000/μL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy.
3. 3. Time to first platelet count of ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and doubled from baseline.
4. 4. Proportion of paticipants requiring rescue therapy during the 24-week blinded treatment period.
5. 5. Change from baseline on Item 10 of the ITPPatient Assessment Questionnaire in adult patients (≥18 years) at Week 13.
6. 6. (EU and UK) Change from baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) assessment at Week 25.
7. 7. Proportion of participants who able to achieve stable platelet response, within a period of 24 weeks following initial achievement of the platelet response.
8. 8. Frequency and severity of Treatment Emergent Adverse Events.
9. 9. Frequency and severity of bleeding TEAEs.
10. 10. Plasma concentrations of rilzabrutinib.
11. 11. Change from baseline on the Symptoms, Bother and Activity domains of the ITP Patient Assessment Questionnaire (ITP-PAQ) in adult patients (≥18 years).
12. 12. Change from baseline in disease-specific QoL as measured by the Kids’ ITP Tools (ITP-KIT) score in pediatric participants.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Principia Biopharma Inc.

Sponsor organisation

Principia Biopharma Inc.

Address

100 Morris Street

City

Morristown

Postcode

07960-4563

Country

United States

Scientific contact point

Organisation

Principia Biopharma Inc.

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Principia Biopharma Inc.

Contact name

Clinical Sciences and Operations

Third parties 7

Locations

7 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications