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

NCT ID: NCT05104892

Last Updated: 2024-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-12
• Study Completion Date: 2024-02-28

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 Background therapy of ICS/LABA will be withdrawn during the 12week randomized treatment period and resumed at the end of the IMP treatment period, as outlined below: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)

Detailed Description

The total study duration per participant is expected to be up to 20 weeks: up to 4 weeks screening, 12 weeks on-treatment double-blind period, and 4-week post-IMP treatment follow up.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rilzabrutinib

Rilzabrutinib BID or TID and ICS/LABA

Group Type: EXPERIMENTAL

Rilzabrutinib

Intervention Type: DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Placebo

Placebo and ICS/LABA

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Interventions

Rilzabrutinib

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type: DRUG

placebo

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type: DRUG

Other Intervention Names

PRN1008/SAR444671

Eligibility Criteria

Inclusion Criteria

• 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 with reversibility of at least 12% and 200 mL in FEV1 15 to 30 minutes after administration of 2 to 4 puffs (200-400 mcg) of albuterol/salbutamol or levalbuterol/levosalbutamol during screening or documented history of a reversibility test that meets this criterion within 5 years prior to Visit 1 or documented positive response to methacholine challenge (a decrease in FEV by 20% [PC20] of <8mg/mL) within 5 years prior to Visit 1/Screening is considered acceptable to meet this inclusion criterion.
• 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.

Exclusion Criteria

• 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.
• Anti-immunoglobulin E (IgE) therapy (e.g., omalizumab [Xolair®]) within 130 days prior to Visit 1 or any other biologic therapy (including anti-IL4/4R or IL-5/5R monoclonal antibodies [mAb]) or systemic immunosuppressant (e.g., methotrexate) to treat inflammatory disease or autoimmune disease (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis) and other diseases, within 2 months or 5 half-lives prior to Visit 1, whichever is longer.
• Use of inhalers other than ICSs, LABAs, and short-acting beta agonists (no long-acting muscarinic antagonists (LAMAs) or mucolytics) and leukotriene receptor antagonists (montelukast, zafirkulast) during the study period.
• Participants who have received bronchial thermoplasty within 2 years prior to Visit 1 or plan to begin therapy during the screening period or the randomized treatment period.
• Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of Day 1.
• Use of known systemic 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.
• Live vaccine except Bacille Calmette Guerinn-vaccination within 28 days prior to Day 1 or plans to receive one during the trial; Calmette Guerin-vaccination within 12 months prior to Screening.
• COVID-19 vaccine within 14 days prior to Study Day 1.
• Previous use of a Bruton tyrosine kinase (BTK) inhibitor.
• Has received any investigational drug (or is currently using an investigational device) within the 30 days before Day 1, or at least 5 times the respective elimination half-life time (whichever is longer).
• Electrocardiogram (ECG) findings of QT corrected for heart rate (QTc) >450 msec (males) or >470 msec (females), poorly controlled atrial fibrillation (i.e., symptomatic patients or a ventricular rate above 100 beats/min on ECG), or other clinically significant cardiovascular abnormalities.
• Active COVID-19 infection as documented by a positive COVID-19 molecular test.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number : 0320004

Berazategui, Buenos Aires, Argentina

Investigational Site Number : 0320006

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320003

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320001

Buenos Aires, , Argentina

Investigational Site Number : 0320005

Ciudad Autonoma Buenos Aires, , Argentina

Investigational Site Number : 0320002

Ciudad Autonoma Buenos Aires, , Argentina

Investigational Site Number : 1000004

Kozloduy, , Bulgaria

Investigational Site Number : 1000001

Rousse, , Bulgaria

Investigational Site Number : 1000003

Sevlievo, , Bulgaria

Investigational Site Number : 1000002

Sofia, , Bulgaria

Investigational Site Number : 1240006

Vancouver, British Columbia, Canada

Investigational Site Number : 1240005

Waterloo, Ontario, Canada

Investigational Site Number : 1520005

Curicó, Maule Region, Chile

Investigational Site Number : 1520002

Talca, Maule Region, Chile

Investigational Site Number : 1520007

Santaigo, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520004

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520003

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number : 1520006

Quillota, Región de Valparaíso, Chile

Investigational Site Number : 6420001

Düsseldorf, , Germany

Investigational Site Number : 3480001

Edelény, , Hungary

Investigational Site Number : 3480004

Hajdunánás, , Hungary

Investigational Site Number : 3480003

Pécs, , Hungary

Investigational Site Number : 4840001

Guadalajara, Jalisco, Mexico

Investigational Site Number : 4840002

Monterrey, Nuevo León, Mexico

Investigational Site Number : 4840005

San Juan del Río, Querétaro, Mexico

Investigational Site Number : 4840003

Durango, , Mexico

Investigational Site Number : 4840004

Veracruz, , Mexico

Investigational Site Number : 6160009

Poznan, Greater Poland Voivodeship, Poland

Investigational Site Number : 6160007

Lublin, Lubusz Voivodeship, Poland

Investigational Site Number : 6160003

Bialystok, Podlaskie Voivodeship, Poland

Investigational Site Number : 6160006

Gdansk, Pomeranian Voivodeship, Poland

Investigational Site Number : 6160005

Bialystok, , Poland

Investigational Site Number : 6160002

Krakow, , Poland

Investigational Site Number : 6160010

Lodz, , Poland

Investigational Site Number : 6160001

Lodz, , Poland

Investigational Site Number : 6160008

Ostrowiec Świętokrzyski, Świętokrzyskie Voivodeship, Poland

Investigational Site Number : 6420002

Cluj-Napoca, , Romania

Investigational Site Number : 4100007

Daegu, Daegu, South Korea

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100005

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100006

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100001

Seoul, , South Korea

Investigational Site Number : 7240004

Santander, Cantabria, Spain

Investigational Site Number : 7240003

Madrid / Madrid, Madrid, Comunidad de, Spain

Investigational Site Number : 7240001

Málaga, , Spain

Investigational Site Number : 7920002

Istanbul, , Turkey (Türkiye)

Investigational Site Number : 7920001

Mersin, , Turkey (Türkiye)

Investigational Site Number : 8260002

Cambridge, Cambridgeshire, United Kingdom

Investigational Site Number : 8260001

Bradford, , United Kingdom

Countries

Argentina; Bulgaria; Canada; Chile; Germany; Hungary; Mexico; Poland; Romania; South Korea; Spain; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39899371 (View on PubMed)

Other Identifiers

U1111-1262-2956

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-002490-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACT17208

Identifier Type: -

Identifier Source: org_study_id