Clinical Trial Page

Summary
EudraCT Number:2022-002959-18
Sponsor's Protocol Code Number:PRN1008-017/ACT17125
National Competent Authority:Spain - AEMPS
Clinical Trial Type:EEA CTA
Trial Status:Prematurely Ended
Date on which this record was first entered in the EudraCT database:2022-12-20
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
A. Protocol Information
A.1Member State ConcernedSpain - AEMPS
A.2EudraCT number2022-002959-18
A.3Full title of the trial
An open label, two-arm, Phase 2a study to evaluate the effect of rilzabrutinib (PRN1008/SAR444671) on safety and disease activity in patients with IgG4-related disease
Estudio de fase IIa, abierto y de dos grupos para evaluar el efecto de rilzabrutinib (PRN1008/SAR444671) sobre la seguridad y la actividad de la enfermedad en pacientes con enfermedad relacionada con la IgG4.
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Open label two-arm study to evaluate rilzabrutinib in IgG4-related disease patients
Estudio abierto de dos grupos para evaluar rilzabrutinib en pacientes con enfermedad relacionada con la IgG4
A.4.1Sponsor's protocol code numberPRN1008-017/ACT17125
A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04520451
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorPrincipia Biopharma Inc
B.1.3.4CountryUnited States
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportPrincipia Biopharma Inc
B.4.2CountryUnited States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationSanofi-Aventis, S.A
B.5.2Functional name of contact pointUnidad de Estudios Clínicos
B.5.3 Address:
B.5.3.1Street AddressC/ Rosselló i Porcel, 21
B.5.3.2Town/ cityBarcelona
B.5.3.3Post code08016
B.5.3.4CountrySpain
B.5.4Telephone number+3493485 94 00
B.5.6E-mailes-unidadestudiosclinicos@sanofi.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product namerilzabrutinib
D.3.2Product code SAR444671
D.3.4Pharmaceutical form Film-coated tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNrilzabrutinib
D.3.9.2Current sponsor codeSAR444671
D.3.9.4EV Substance CodeSUB192772
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number400
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
IgG4-related disease
Enfermedad relacionada con la IgG4
E.1.1.1Medical condition in easily understood language
Immunoglobulin G4 related disease
Enfermedad relacionada con la inmunoglobulina G4
E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10077271
E.1.2Term Immunoglobulin G4 related disease
E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
To evaluate the safety and the ability of daily oral administration of rilzabrutinib to maintain glucocorticoid-free remission in participants with IgG4-RD for at least 24 weeks
Evaluar la seguridad y la capacidad de la administración oral diaria de rilzabrutinib para mantener la remisión libre de glucocorticoides en participantes con IgG4-RD durante al menos 24 semanas
E.2.2Secondary objectives of the trial
- To evaluate the effect of rilzabrutinib on IgG4-RD disease activity over time
- To evaluate the effect of rilzabrutinib on specific protein biomarkers over time
- Evaluar el efecto de rilzabrutinib sobre la actividad de la enfermedad IgG4-RD a lo largo del tiempo
- Evaluar el efecto de rilzabrutinib en biomarcadores proteicos específicos a lo largo del tiempo
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
- Be male or female with age ≥18 years.
- Have a clinical diagnosis of IgG4-RD.
- Be willing to taper off an equivalent prednisone dose of between 20-40 mg/day in 2 weeks.
- Ser hombre o mujer con edad ≥18 años.
- Tener un diagnóstico clínico de IgG4-RD.
- Estar dispuesto a disminuir una dosis equivalente de prednisona entre 20-40 mg/día en 2 semanas
E.4Principal exclusion criteria
- Currently or within 6 months of screening taking rituximab, other B-cell depleting agents, or alkylating agents unless B cell concentrations have been demonstrated by flow cytometry to return to normal values (defined as 5 cells per cubic mm).
- History of solid organ transplant
- Positive at Screening for HIV, hepatitis B, hepatitis C, or TB
- Female patients who are pregnant or nursing.
- Actualmente o dentro de los 6 meses posteriores a la selección tomando rituximab, otros agentes que reducen las células B o agentes alquilantes, a menos que se haya demostrado que las concentraciones de células B vuelven a los valores normales (definidas como 5 células por mm cúbico) mediante citometría de flujo.
- Historial de trasplante de órgano sólido
- Positivo en la prueba de detección de VIH, hepatitis B, hepatitis C o TB
- Mujeres que están embarazadas o amamantando.
E.5 End points
E.5.1Primary end point(s)
1. Proportion of participants who are without disease flare for at least 24 consecutive weeks following the first dose of rilzabrutinib. Disease flare is defined as an increase from screening IgG4-RD responder index (RI) >2 or initiation of rescue treatment.
2. Incidence of SAE, AE leading to discontinuation and possible glucocorticoid-related AE.
3. Number of participants with Potentially clinically significant abnormalities (PCSAs) for clinical laboratory tests, vital signs and ECG
1. Proporción de participantes sin brotes de la enfermedad durante al menos 24 semanas consecutivas tras la primera dosis de rilzabrutinib. El brote de la enfermedad se define como un aumento del índice de respuesta (IR) de IgG4-RD de detección > 2 o el inicio del tratamiento de rescate.
2. Incidencia de SAE, AE que lleva a la interrupción y posible AE relacionado con glucocorticoides.
3. Número de participantes con anomalías potenciales clínicamente significativas (PCSA) para pruebas clínicas de laboratorio, signos vitales y ECG
E.5.1.1Timepoint(s) of evaluation of this end point
1. At Week 52
2, 3. Up to 68 weeks
1. En la semana 52
2, 3. Hasta 68 semanas
E.5.2Secondary end point(s)
1. Proportion of participants with reduction from baseline IgG4-RD RI activity score ≥2 points at Week 12
2. Proportion of patients with an IgG4-RD RI activity score = 0 at Week 12
3. Level and change from baseline of each subclass of the serological markers
4. Proportion of participants achieving reduction in baseline serum IgG4 level of 10% at 12 weeks
5. Change from baseline in IgG4-RD RI over time
6. Proportion of participants with no disease flares between Week 4 and Week 12, and between Week 12 and Week 52 (or the end of the treatment extension period) among the participants who have treatment extension
7. Change from baseline over time in IgG4-RD damage, as recorded on the damage portion of the IgG4-RD RI
1.Proporción de participantes con una reducción en la puntuación de la actividad del IR de la ER-IgG4 ≥2 puntos en la semana 12 con respecto al momento inicial.

2. Proporción de participantes con una puntuación de la actividad del IR de la ER-IgG4 igual a 0 en la semana 12.
3. Nivel y cambio desde el inicio de cada subclase de los marcadores serológicos
4. Proporción de participantes que logren una reducción en el nivel inicial de IgG4 en suero del 10 % a las 12 semanas.
5. Cambio con respecto al momento inicial en el IR de la ER-IgG4 a lo largo del tiempo.
6. Proporción de participantes sin reagudizaciones de la enfermedad entre las semanas 4 y 12, y entre las semanas 12 y 52 (o el final del periodo de tratamiento de mantenimiento) en los participantes que tengan una prolongación del tratamiento.
7. Cambio con respecto al momento inicial en el daño de la ER-IgG4, registrado en la parte de daño del IR de la ER-IgG4, a lo largo del tiempo.
E.5.2.1Timepoint(s) of evaluation of this end point
1, 2, 3. At Week 52
4. At Week 12
5, 7. From baseline to Week 52
6. Until Week 52
1, 2, 3. En la semana 52
4. En la semana 12
5, 7. Desde el inicio hasta la semana 52
6. Hasta la semana 52
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned1
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA3
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Canada
United States
France
Spain
Italy
E.8.7Trial 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
LVLS
La última visita del último paciente
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years2
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years4
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days27
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 25
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state1
F.4.2 For a multinational trial
F.4.2.1In the EEA 5
F.4.2.2In the whole clinical trial 25
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
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-03-23
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-03-21
P. End of Trial
P.End of Trial StatusPrematurely Ended

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe