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AsthmaPhase 2NCT05104892

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

A Phase 2 study testing Rilzabrutinib in people with Asthma, run by Sanofi at 51 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Asthma
What is being tested?
Rilzabrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
196 participants
Where
51 sitesin 13 countries
Study dates
12 Dec 2021to 28 Feb 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 27Show fewer
  • 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.

Trial locations and contacts

51 sites in 13 countries.

51 sites in 13 countries

Poland9 sites

  • Investigational Site Number : 6160003

    Bialystok, Podlaskie Voivodeship, 15-044

  • Investigational Site Number : 6160005

    Bialystok, 15010

  • Investigational Site Number : 6160006

    Gdansk, Pomeranian Voivodeship, 80-214

  • Investigational Site Number : 6160002

    Krakow, 30-033

  • Investigational Site Number : 6160010

    Lodz, 90-752

  • Investigational Site Number : 6160001

    Lodz, 90141

  • Investigational Site Number : 6160007

    Lublin, Lubusz Voivodeship, 20-362

  • Investigational Site Number : 6160008

    Ostrowiec Świętokrzyski, Świętokrzyskie Voivodeship, 27-400

  • Investigational Site Number : 6160009

    Poznan, Greater Poland Voivodeship, 61-578

Other trials in Poland

Chile7 sites

  • Investigational Site Number : 1520005

    Curicó, Maule Region, 3341643

  • Investigational Site Number : 1520006

    Quillota, Valparaiso, 2260877

  • Investigational Site Number : 1520007

    Santaigo, Reg Metropolitana de Santiago, 8241470

  • Investigational Site Number : 1520001

    Santiago, Reg Metropolitana de Santiago, 7500692

  • Investigational Site Number : 1520004

    Santiago, Reg Metropolitana de Santiago, 7500698

  • Investigational Site Number : 1520003

    Santiago, Reg Metropolitana de Santiago, 8910131

  • Investigational Site Number : 1520002

    Talca, Maule Region

Other trials in Chile

Argentina6 sites

  • Investigational Site Number : 0320004

    Berazategui, Buenos Aires, CP 1884

  • Investigational Site Number : 0320001

    Buenos Aires, C1121ABE

  • Investigational Site Number : 0320006

    CABA, Buenos Aires, C1122AAK

  • Investigational Site Number : 0320003

    CABA, Buenos Aires, C1425FVH

  • Investigational Site Number : 0320005

    Ciudad Autonoma Buenos Aires, C1414AIF

  • Investigational Site Number : 0320002

    Ciudad Autonoma Buenos Aires, C1425BEN

Other trials in Argentina

South Korea6 sites

  • Investigational Site Number : 4100007

    Daegu, Daegu, 705-717

  • Investigational Site Number : 4100004

    Seoul, Seoul-teukbyeolsi, 03312

  • Investigational Site Number : 4100005

    Seoul, Seoul-teukbyeolsi, 05030

  • Investigational Site Number : 4100002

    Seoul, Seoul-teukbyeolsi, 05505

  • Investigational Site Number : 4100006

    Seoul, Seoul-teukbyeolsi, 08308

  • Investigational Site Number : 4100001

    Seoul, 06591

Other trials in South Korea

Mexico5 sites

  • Investigational Site Number : 4840003

    Durango, 34000

  • Investigational Site Number : 4840001

    Guadalajara, Jalisco, 44100

  • Investigational Site Number : 4840002

    Monterrey, Nuevo León, 64460

  • Investigational Site Number : 4840005

    San Juan del Río, Querétaro, 76800

  • Investigational Site Number : 4840004

    Veracruz, 91910

Other trials in Mexico

Bulgaria4 sites

  • Investigational Site Number : 1000004

    Kozloduy, 3320

  • Investigational Site Number : 1000001

    Rousse, 7002

  • Investigational Site Number : 1000003

    Sevlievo, 5400

  • Investigational Site Number : 1000002

    Sofia, 1612

Other trials in Bulgaria

Hungary3 sites

  • Investigational Site Number : 3480001

    Edelény, 3780

  • Investigational Site Number : 3480004

    Hajdunánás, 4080

  • Investigational Site Number : 3480003

    Pécs, 7635

Other trials in Hungary

Spain3 sites

  • Investigational Site Number : 7240003

    Madrid / Madrid, Madrid, Comunidad de, 28007

  • Investigational Site Number : 7240001

    Málaga, 29010

  • Investigational Site Number : 7240004

    Santander, Cantabria, 39008

Other trials in Spain

Canada2 sites

  • Investigational Site Number : 1240006

    Vancouver, British Columbia, V5Z 1M9

  • Investigational Site Number : 1240005

    Waterloo, Ontario, N2J 1C4

Other trials in Canada

Turkey (Türkiye)2 sites

  • Investigational Site Number : 7920002

    Istanbul, 34303

  • Investigational Site Number : 7920001

    Mersin, 33070

Other trials in Turkey (Türkiye)

United Kingdom2 sites

  • Investigational Site Number : 8260001

    Bradford, BD9 6RJ

  • Investigational Site Number : 8260002

    Cambridge, Cambridgeshire, CB2 OQQ

Other trials in United Kingdom

Germany1 site

  • Investigational Site Number : 6420001

    Düsseldorf, 40225

Other trials in Germany

Romania1 site

  • Investigational Site Number : 6420002

    Cluj-Napoca, 400012

Other trials in Romania

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, 12 Week Proof-of-Concept (PoC) Study to Assess the Efficacy, Safety, and Tolerability of Rilzabrutinib in Participants With Moderate-to-severe Asthma Who Are Not Well Controlled on Inhaled Corticosteroid (ICS) Plus Long-acting β2 Adrenergic Agonist (LABA) Therapy

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)
Read the 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
Being tested
Rilzabrutinib, placebo
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RilzabrutinibDrug

    Also called PRN1008/SAR444671

    Pharmaceutical form: Tablet Route of administration: Oral

  • placeboDrug

    Pharmaceutical form: Tablet Route of administration: Oral

Study groups in NCT05104892
Study groupRoleWhat they receive
RilzabrutinibExperimentalRilzabrutinib BID or TID and ICS/LABA
Receives: Drug: Rilzabrutinib
PlaceboPlacebo comparatorPlacebo and ICS/LABA
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Until Week 12

Secondary outcomes (11)

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

    Measured: From baseline to Week 12

  2. Post-bronchodilator FEV1 change from baseline to EOT

    Measured: From baseline to Week 12

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

    Measured: From baseline to Week 12

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

    Measured: From baseline until Week 12

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

    Measured: From baseline until Week 12

  6. Asthma Control Questionnaire-5 (ACQ-5) score change from baseline at EOT and at each assessment time point

    The ACQ-5 is a questionnaire that measures the adequacy of asthma control and any changes in asthma control that may occur spontaneously or as a result of treatment. The ACQ-5 has five questions on the asthma symptoms and patients are asked to recall how their asthma has been during the previous week and to respond on a 7-point scale for each question (0 = no impairment, 6 = maximum impairment). The ACQ-5 score is the mean of the 5 questions and, therefore, between 0 (totally controlled) and 6 (severely uncontrolled). A high score indicates low asthma control.

    Measured: From baseline until Week 12

  7. Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ[S]) Self-administered score change from baseline at EOT and at each assessment time point

    The AQLQ(S) was designed as a self-administered patient reported outcome to measure the functional impairments that are most troublesome to adolescents and adults ≥12 years of age as a result of their asthma. The instrument is comprised of 32 items, each rated on a 7-point Likert scales from 1 to 7. Higher scores indicate better quality of life.

    Measured: From baseline until Week 12

  8. Change in Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) scores from baseline to EOT and each week

    ADSD and ANSD assess asthma severity based on patient self-report of asthma core symptoms, i.e., difficulty of breathing; wheezing; shortness of breath; chest tightness; chest pain; and cough. Both the ADSD and ANSD are composed of 6 items rated using an 11-point numerical rating scale (NRS) that ranges from 0 = None to 10 = As bad as you can imagine. The participants will record their daytime and nighttime asthma symptoms in an electronic diary, once in the evening and once in the morning, respectively.

    Measured: From baseline until Week 12

  9. Plasma pharmacokinetic (PK) concentrations of rilzabrutinib in participants with asthma

    Measured: Until Week 16

  10. Participants with Treatment Emergent Adverse Events

    Measured: Until Week 16

  11. Change in numbers of inhalations/day of albuterol or levalbuterol for symptom relief from baseline to EOT and each week

    Measured: From baseline until Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2021
  2. Study start12 Dec 2021
  3. Primary completion6 Feb 2024
  4. Study completion28 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
196 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05104892
Sponsor's protocol ID
ACT17208
Other IDs
U1111-1262-2956, 2021-002490-26
Status last verified
Mar 2024
First submitted
17 Oct 2021
Last updated
7 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Maspero JF, Pavord ID, Wechsler ME, Busse W, Laidlaw TM, Mroz RM, Liu T, Mikol V, Suratt BT, Gereige J, Mannent L, Martincova R. Rilzabrutinib for patients with moderate-to-severe asthma with uncontrolled symptoms: a double-blind, placebo-controlled, phase 2 study. Lancet Respir Med. 2026 May;14(5):405-416. doi: 10.1016/S2213-2600(25)00439-4. Epub 2026 Apr 2.

    PubMed 41936356

  • 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.

    PubMed 39899371

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rilzabrutinib in people with Asthma, run by Sanofi at 51 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in Poland, Chile, Argentina, South Korea, Mexico and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants with an LOAC event during the treatment period (time frame: Until Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05104892, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2024.

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