Proof of Concept Study of Rilzabrutinib in Adult Participants With Moderate-to-severe Asthma

NCT05104892 | Completed Phase 2

• 3 other identifiers: ACT17208U1111-1262-29562021-002490-26
• Study Type: interventional
• Target: 196
• Locations: 13 countries
• Sites: 51

Brief Summary

This is a parallel, treatment, Phase 2, double-blind, 2 arm, 12-week Proof of Concept (PoC) study with 2 staggered cohorts (2 arms in each cohort) that is designed to assess the efficacy, safety, and tolerability of rilzabrutinib in adult participants (aged 18-70 years) with moderate-to-severe asthma who are not well controlled on ICS/LABA therapy. Study treatment includes investigational medicinal product (IMP) (rilzabrutinib or placebo) added-on to a background therapy of ICS/LABA (fluticasone/salmeterol \[non-investigational medicinal product\], standardized at screening). Background therapy of ICS/LABA will be withdrawn during the 12week randomized treatment period and resumed at the end of the IMP treatment period, as outlined below:

• Screening period (4 weeks)
• Randomized IMP treatment period (12 weeks ± 3 days)
• Background therapy stabilization phase (4 weeks)
• Background therapy withdrawal phase (4-5 weeks)
• No background therapy phase (3-4 weeks)
• Post IMP treatment safety follow-up period (4 weeks ± 3 days)

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with an LOAC event during the treatment period

  Loss of Asthma Control (LOAC) event is defined as any of the following: * A 30% or greater reduction from baseline in morning peak expiratory flow (PEF) on 2 consecutive days * ≥6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days * Increase in ICS ≥4 times the last prescribed ICS dose (or ≥50% of the prescribed ICS dose at V2 if background therapy withdrawal completed) * Requiring use of systemic (oral and/or parenteral) steroid treatment * Requiring hospitalization or emergency room visit for asthma exacerbation

  Until Week 12

Secondary Outcomes (11)

• Pre-bronchodilator FEV1 (Forced expiratory volume in one second) change from baseline to EOT (end of treatment)

  From baseline to Week 12

• Post-bronchodilator FEV1 change from baseline to EOT

  From baseline to Week 12

• The absolute change in the percent predicted FEV1 from baseline to EOT (pre- and post-bronchodilator)

  From baseline to Week 12

• Change from baseline in pre- and post-bronchodilator FEV1 and forced vital capacity [FVC] at each spirometry endpoint

  From baseline until Week 12

• Change from baseline in peak expiratory flow [PEF] and forced expiratory flow [FEF] 25-75% at each spirometry endpoint

  From baseline until Week 12

Study Arms (2)

Rilzabrutinib

EXPERIMENTAL

Rilzabrutinib BID or TID and ICS/LABA

Drug: Rilzabrutinib

Placebo

PLACEBO COMPARATOR

Placebo and ICS/LABA

Drug: placebo

Interventions

Rilzabrutinib DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Also known as: PRN1008/SAR444671

Rilzabrutinib

placebo DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A physician diagnosis of asthma for at least 12 months based on the Global Initiative for Asthma (GINA) 2018,2019, 2020 Guidelines.
• Participants with existing treatment with at least moderate to high doses of ICS therapy in combination with a LABA as second controller for at least 3 months with a stable dose ≥1 month prior to Visit 1.
• Participants with prebronchodilator FEV1 \>40% of predicted normal at Visit 1/Screening. Prebronchodilator FEV1 ≥50% of predicted normal at Visit 2/Baseline.
• Participants must have experienced, within 2 years prior to Visit 1, any of the following asthma exacerbation events at least once: Treatment with a systemic steroid (oral or parenteral) for worsening asthma OR Hospitalization or emergency medical care visit for worsening asthma.
• Body mass index (BMI) ≥17.5 and ≤40 kg/m2
• All Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Participants must have completed COVID-19 vaccination per current regional health authority recommendations prior to screening.

You may not qualify if:

• History of serious infections requiring intravenous therapy with the potential for recurrence (as judged by Site Investigator), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate-to-severe infection at Screening (Grade 2 or higher).
• Chronic lung disease (for example, chronic obstructive pulmonary disease \[COPD\], or idiopathic pulmonary fibrosis \[IPF\]) which may impair lung function, or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts, for e.g. eosinophilic granulomatosis with polyangiitis.
• History of life-threatening asthma (i.e., severe exacerbation that requires intubation).
• Participants with any of the following events within the 4 weeks prior to their Screening Visit 1 or during the screening period: Treatment with 1 or more systemic (oral and/or parenteral) steroid bursts for worsening asthma OR Hospitalization or emergency medical care visit for worsening asthma
• Asthma Control Questionnaire 5-question version (ACQ-5) score \<1.25 or \>3.0 at V2/randomization. During the screening period an ACQ-5 of up to ≤4 is acceptable.
• Current smoker or cessation of smoking within the 6 months prior to Visit 1.
• Previous smoker with a smoking history \>10 pack-years.
• Current or chronic history of liver disease.
• Known hepatic or biliary abnormalities, e.g. moderate or severe hepatic impairment, such as Child Pugh B or C
• Symptomatic herpes zoster within 3 months prior to screening.
• Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
• Conditions that may predispose the participant to excessive bleeding
• History of solid organ transplant.
• A history of malignancy of any type within 5 years before Day 1, other than surgically excised non-melanoma skin cancers or in situ cervical cancer.
• Is not up-to-date with recommended vaccinations per local guidelines.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (51)

Investigational Site Number : 0320004

Berazategui, Buenos Aires, CP 1884, Argentina

Location

Investigational Site Number : 0320006

CABA, Buenos Aires, C1122AAK, Argentina

Location

Investigational Site Number : 0320003

CABA, Buenos Aires, C1425FVH, Argentina

Location

Investigational Site Number : 0320001

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number : 0320005

Ciudad Autonoma Buenos Aires, C1414AIF, Argentina

Location

Investigational Site Number : 0320002

Ciudad Autonoma Buenos Aires, C1425BEN, Argentina

Location

Investigational Site Number : 1000004

Kozloduy, 3320, Bulgaria

Location

Investigational Site Number : 1000001

Rousse, 7002, Bulgaria

Location

Investigational Site Number : 1000003

Sevlievo, 5400, Bulgaria

Location

Investigational Site Number : 1000002

Sofia, 1612, Bulgaria

Location

Investigational Site Number : 1240006

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Investigational Site Number : 1240005

Waterloo, Ontario, N2J 1C4, Canada

Location

Investigational Site Number : 1520005

Curicó, Maule Region, 3341643, Chile

Location

Investigational Site Number : 1520002

Talca, Maule Region, Chile

Location

Investigational Site Number : 1520007

Santaigo, Reg Metropolitana de Santiago, 8241470, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 7500692, Chile

Location

Investigational Site Number : 1520004

Santiago, Reg Metropolitana de Santiago, 7500698, Chile

Location

Investigational Site Number : 1520003

Santiago, Reg Metropolitana de Santiago, 8910131, Chile

Location

Investigational Site Number : 1520006

Quillota, Región de Valparaíso, 2260877, Chile

Location

Investigational Site Number : 6420001

Düsseldorf, 40225, Germany

Location

Investigational Site Number : 3480001

Edelény, 3780, Hungary

Location

Investigational Site Number : 3480004

Hajdunánás, 4080, Hungary

Location

Investigational Site Number : 3480003

Pécs, 7635, Hungary

Location

Investigational Site Number : 4840001

Guadalajara, Jalisco, 44100, Mexico

Location

Investigational Site Number : 4840002

Monterrey, Nuevo León, 64460, Mexico

Location

Investigational Site Number : 4840005

San Juan del Río, Querétaro, 76800, Mexico

Location

Investigational Site Number : 4840003

Durango, 34000, Mexico

Location

Investigational Site Number : 4840004

Veracruz, 91910, Mexico

Location

Investigational Site Number : 6160009

Poznan, Greater Poland Voivodeship, 61-578, Poland

Location

Investigational Site Number : 6160007

Lublin, Lubusz Voivodeship, 20-362, Poland

Location

Investigational Site Number : 6160003

Bialystok, Podlaskie Voivodeship, 15-044, Poland

Location

Investigational Site Number : 6160006

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Investigational Site Number : 6160005

Bialystok, 15010, Poland

Location

Investigational Site Number : 6160002

Krakow, 30-033, Poland

Location

Investigational Site Number : 6160010

Lodz, 90-752, Poland

Location

Investigational Site Number : 6160001

Lodz, 90141, Poland

Location

Investigational Site Number : 6160008

Ostrowiec Świętokrzyski, Świętokrzyskie Voivodeship, 27-400, Poland

Location

Investigational Site Number : 6420002

Cluj-Napoca, 400012, Romania

Location

Investigational Site Number : 4100007

Daegu, Daegu, 705-717, South Korea

Location

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, 03312, South Korea

Location

Investigational Site Number : 4100005

Seoul, Seoul-teukbyeolsi, 05030, South Korea

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 05505, South Korea

Location

Investigational Site Number : 4100006

Seoul, Seoul-teukbyeolsi, 08308, South Korea

Location

Investigational Site Number : 4100001

Seoul, 06591, South Korea

Location

Investigational Site Number : 7240004

Santander, Cantabria, 39008, Spain

Location

Investigational Site Number : 7240003

Madrid / Madrid, Madrid, Comunidad de, 28007, Spain

Location

Investigational Site Number : 7240001

Málaga, 29010, Spain

Location

Investigational Site Number : 7920002

Istanbul, 34303, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Mersin, 33070, Turkey (Türkiye)

Location

Investigational Site Number : 8260002

Cambridge, Cambridgeshire, CB2 OQQ, United Kingdom

Location

Investigational Site Number : 8260001

Bradford, BD9 6RJ, United Kingdom

Location

Related Publications (1)

• Lin J, Radhakrishnan J. What Are Baskets, Umbrellas, and Platforms Doing in Nephrology Clinical Trials? J Am Soc Nephrol. 2025 Feb 3;36(8):1652-1654. doi: 10.1681/ASN.0000000648. No abstract available.

  PMID: 39899371 DERIVED

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2021
• First Posted: November 3, 2021
• Study Start: December 12, 2021
• Primary Completion: February 6, 2024
• Study Completion: February 28, 2024
• Last Updated: March 7, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

TU (2); ME (5); HU (3); GB (2); CL (7); DE (1); BU (4); CA (2); RO (1); KR (6); PL (9); AR (6); ES (3)