Clinical Trials Register

Summary
EudraCT Number:	2020-002063-60
Sponsor's Protocol Code Number:	PRN1008-018(EFC17093)
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-10-01
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2020-002063-60

A.3

Full title of the trial

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.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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)

A.4.1

Sponsor's protocol code number

PRN1008-018(EFC17093)

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04562766

A.5.4

Other Identifiers

Name:

IND

Number:

132668

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/262/2022

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Principia Biopharma, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Principia Biopharma, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Principia Biopharma, Inc.
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	55 Corporate Drive
B.5.3.2	Town/ city	Bridgewater
B.5.3.3	Post code	NJ 08807
B.5.3.4	Country	United States
B.5.4	Telephone number	+18009812491
B.5.6	E-mail	Antonia.Martinez@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/20/2278
D.3 Description of the IMP
D.3.1	Product name	Rilzabrutinib
D.3.2	Product code	PRN1008
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rilzabrutinib
D.3.9.1	CAS number	1575591-66-0
D.3.9.2	Current sponsor code	PRN1008
D.3.9.4	EV Substance Code	SUB192772
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Immune Thrombocytopenia (ITP)

E.1.1.1

Medical condition in easily understood language

Immune Thrombocytopenia (ITP) is a chronic, autoimmune disease that is associated with bleeding risk due to low platelet levels in the blood.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10074667
E.1.2	Term	Immune thrombocytopenic purpura
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

•To demonstrate the efficacy of rilzabrutinib (PRN1008) 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.

E.2.2

Secondary objectives of the trial

• Effect of PRN1008 vs PbO on:
- the nb of weeks w/ platelet count ≥50,000/μL OR btw ≥30,000<50,000/μL & at least doubled from baseline, over the 24-week blinded treatment period in the absence of rescue therapy
- the nb of weeks w/ platelet count ≥30,000/μL & at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy
- the time to 1st platelet count of ≥50,000/μL OR btw ≥30,000<50,000/μL & at least doubled from baseline
- the nb of patients requiring rescue therapy during the 24-week treatment period
- the change from baseline on ITP-Patient Assessment Questionnaire (ITP-PAQ) Item 10 in adults at Week 13
• Change from baseline in IBLS
• Nb of patients with stable platelet response
• Safety & tolerability of PRN1008
• PK of PRN1008
• Change from baseline in QoL ITP PAQ & ITP Kit

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participants 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. 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 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. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥ 1.5 X 10^9/L, AST/ALT ≤ 1.5 x ULN, albumin ≥ 3 g/dL, total bilirubin ≤ 1.5 x ULN, estimated GFR > 50 [Cockcroft and Gault method]
5. Hemoglobin (Hgb) > 9 g/dL prior to dosing on Study Day 1
6. Female patients who are of reproductive potential (fertile, following menarche and until becoming post-menopausal unless permanently sterile) or are likely to reach reproductive potential during the study must agree for the duration of the study to use an effective means of contraception (eg. hormonal contraception methods that inhibit ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized partner or condoms) or practice true abstinence (when this is in line with the usual and preferred lifestyle). For females considered not to have reproductive potential: Any woman of age ≥ 55 years with amenorrhea for >1 year, will be considered as having confirmed menopause and follicle-stimulating hormone (FSH) or pregnancy testing will not be needed. Postmenopausal females <55 years of age (defined as amenorrhea > 1 year) must have menopause confirmed by elevated FSH levels at Screening. Surgically sterile females do not require any further confirmation of menopause and will not be considered to have reproductive potential.
7. Participants 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.

E.4

Principal exclusion criteria

1. Participants with secondary ITP
2. Pregnant or lactating women
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
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
5. Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses)
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
7. Treatment with rituximab or splenectomy within the 3 months prior to Study Day 1
- Participants treated with rituximab will have normal B-cell counts prior to enrollment
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
- Participants 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
- Participants who previously received rilzabrutinib at any time are not eligible
9. History of solid organ transplant
10. Myelodysplastic syndrome
11. Live vaccine within 28 days prior to Study Day 1 or plan to receive one during the study
12. Planned surgery in the time frame of the dosing period

E.5 End points

E.5.1

Primary end point(s)

Proportion of 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 in the absence of rescue therapy

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

E.5.2

Secondary end point(s)

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. 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. Time to first platelet count of ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and doubled from baseline
4. Proportion of participants requiring rescue therapy during the 24-week blinded treatment period
5. Change from baseline on Item 10 of the ITP-Patient Assessment Questionnaire in adult patients (≥18 years) at Week 13
6. Change from baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) assessment at Week 25
7. Proportion of participants who able to achieve stable platelet response, within a period of 24 weeks following initial achievement of the platelet response. Stable platelet response is defined as no 2 scheduled visits, at least 4 weeks apart, with a platelet count less than 50,000/µL, without an intervening visit with a platelet count ≥50,000/µL. Initial platelet response defined as platelet count ≥50,000/μL within 12 weeks of initiation of treatment with rilzabrutinib during the study.
8. Frequency and severity of Treatment Emergent Adverse Events. Including physical examination, ECG, clinical laboratory test results, vital signs and laboratory tests (serum chemistry, hematology, except for platelet counts included in the primary efficacy endpoint)
9. Frequency and severity of bleeding TEAEs
10. Plasma concentrations of rilzabrutinib
11. Change from baseline on the Symptoms, Bother and Activity domains of the ITP Patient Assessment Questionnaire (ITP-PAQ) in adult patients (≥18 years). The ITP Patient Assessment Questionnaire™ (ITP-PAQ™) is a disease-specific instrument that was designed to measure the Quality of Life (QoL) of adult patients with immune thrombocytopenia. The items employ a 4-week recall with responses recorded on 4-, 5- or 7-point Likert scales. All item scores are transformed to a 0 to 100 continuum where higher scores represent better QoL and are weighted equally to derive the scale scores.
12. Change from baseline in disease-specific QoL as measured by the Kids' ITP Tools (ITP-KIT) score in pediatric participants. The ITP-KIT include a battery of three disease-specific instruments, a child selfreport form designed to be completed by children ≥7 years, a parent proxy report form for children <7 and a parent impact form. Respondents record their disease experience based on a 1-week recall. The instrument yields a total score which is the summation of the items converted to a 0 to 100 score with higher scores indicating better disease-specific QoL.

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 2, 3, 4, 7. 24 weeks
5. From baseline to Week 13
6. At Week 25
8, 9, 11, 12. 52 weeks of treatment, long term extension and 4 weeks of follow up post last dose
10. Until 52 weeks

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Chile

Singapore

Ukraine

Australia

Brazil

Canada

China

Israel

Japan

Korea, Republic of

Mexico

Russian Federation

Thailand

United Kingdom

United States

Austria

France

Germany

Hungary

Italy

Norway

Poland

Spain

Türkiye

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of trial is defined as the point at which the last patient has completed final assessments at the last visit of the study (LPLV).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

169

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

224

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Medical Research Network Ltd
G.4.3.4	Network Country	United Kingdom

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-11-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-11-12

P. End of Trial
P.	End of Trial Status	Ongoing

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