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    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2021-002490-26
    Sponsor's Protocol Code Number:ACT17208
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2023-03-08
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBulgarian Drug Agency
    A.2EudraCT number2021-002490-26
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Proof of concept study of rilzabrutinib in adult participants with moderate-to-severe asthma
    A.4.1Sponsor's protocol code numberACT17208
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1262-2956
    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 SponsorSanofi aventis recherche et developpement
    B.1.3.4CountryFrance
    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 supportSanofi Aventis Recherche et Developpement
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 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.3.9.3Other descriptive namePRN1008
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Asthma
    E.1.1.1Medical condition in easily understood language
    Asthma
    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 SOC
    E.1.2Classification code 10038738
    E.1.2Term Respiratory, thoracic and mediastinal disorders
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • Evaluate the effects of rilzabrutinib compared to placebo on reducing the incidence of “loss of asthma control” (LOAC) events
    E.2.2Secondary objectives of the trial
    • Evaluate the effects of rilzabrutinib compared to placebo on lung function as measured by FEV1
    • Assess the effects of rilzabrutinib on other elements of spirometric lung function
    • Assess the effect of rilzabrutinib on patient reported outcomes
    • Assess the effects of rilzabrutinib on asthma symptoms
    • Assess the plasma pharmacokinetic (PK) of rilzabrutinib in participants with asthma
    • Assess the safety of rilzabrutinib in participants with asthma
    • Assess the effects of rilzabrutinib on use of bronchodilator therapy
    E.2.3Trial contains a sub-study No
    E.3Principal 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.
    E.4Principal 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 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.
    E.5 End points
    E.5.1Primary end point(s)
    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 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
    E.5.1.1Timepoint(s) of evaluation of this end point
    Until Week 12
    E.5.2Secondary end point(s)
    1 - Pre-bronchodilator FEV1 (Forced expiratory volume in one second) change from baseline to EOT (end of treatment)
    2 - Post-bronchodilator FEV1 change from baseline to EOT
    3 - The absolute change in the percent predicted FEV1 from baseline to EOT (pre- and post-bronchodilator)
    4 - Change from baseline in pre- and post-bronchodilator FEV1 and other lung function measurements at each spirometry endpoint ; Other lung function measure includes peak expiratory flow [PEF], forced vital capacity [FVC], and forced expiratory flow [FEF] 25-75%)
    5 - 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.
    6 - 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.
    7 - 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 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.
    8 - Plasma PK concentrations of rilzabrutinib in participants with asthma
    9 - Participants with Treatment Emergent Adverse Events
    10 - Change in numbers of inhalations/day of albuterol or levalbuterol for symptom relief from baseline to EOT and each week
    E.5.2.1Timepoint(s) of evaluation of this end point
    1, 2, 3 - From baseline to Week 12
    4 ,5, 6, 7 - From baseline until Week 12
    8, 9 - Until Week 16
    10 - From baseline until Week 12
    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 No
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    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
    Argentina
    Chile
    Ukraine
    Bulgaria
    Canada
    Hungary
    Korea, Republic of
    Mexico
    Poland
    Romania
    Russian Federation
    Spain
    Turkey
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months25
    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: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 state70
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 96
    F.4.2.2In the whole clinical trial 320
    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 Decision2023-03-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-04-19
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2024-02-28
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