A Study to Test if TEV-48574 is Effective in Relieving Asthma

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to evaluate the effect of TEV-48574 compared with placebo on loss of asthma control (LoAC) in adult participants with T2-low and non-T2 severe asthma uncontrolled on inhaled corticosteroids plus long-acting beta-agonists (ICS+LABA). The secondary efficacy objective is to evaluate the effect of TEV-48574 compared with placebo on a range of clinical measures of asthma control. The duration of participant participation in the study is planned to be up to approximately 30 weeks.

Official Title
-----------------
A 16-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Proof-of-Concept Study to Evaluate the Efficacy and Safety of TEV-48574 in Adults With T2-low/Non-T2 Severe Uncontrolled Asthma

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: TEV-48574
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The participant has a diagnosis of asthma for at least 12 months prior to the initial screening visit. The participant is able to perform technically acceptable and repeatable spirometry, including with a hand-held spirometer, after training The participant has had at least one documented clinical asthma exacerbation in the 18 months prior to (but not within 30 days of) the initial screening visit. The participant is a non-smoker for ≥6 months with lifetime history ≤10 pack-years, with no current ecigarette or marijuana use. NOTE- Additional criteria apply, please contact the investigator for more information Exclusion Criteria: The participant has any concomitant conditions or treatments that could interfere with study conduct. The participant is currently pregnant or lactating or is planning to become pregnant during the study. The participant has received any live or attenuated vaccine within 15 days of the initial screening visit. NOTE- Additional criteria apply, please contact the investigator for more information

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEV-48574<br>Participants will receive the investigational medicinal product (IMP) loading doses on the day of randomization and the subsequent corresponding IMP maintenance doses every 2 weeks for a total of 8 doses (1 loading dose and 7 maintenance doses). | Drug: TEV-48574<br>* subcutaneous infusion<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to TEV-48574 SC every 2 weeks for a total of 8 doses. | Drug: Placebo<br>* Matching Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Loss of Asthma Control (LoAC) During the Treatment Period | The LoAC was defined as any 1 of the following during the treatment period: - morning peak expiratory flow (PEF) decrease ≥30% from baseline on 2 consecutive days or morning handheld forced expiratory volume in the first second of exhalation (FEV1) decrease ≥20% from baseline on 2 consecutive days; - increase in short-acting beta-agonist (SABA)/quick-relief medication ≥6 puffs over baseline use in 24 hours on 2 consecutive days; increase in inhaled corticosteroids (ICS) dose ≥4 × most recent dose; - systemic corticosteroid use; - asthma emergency room (ER) visit or hospitalization. | From randomization (Week 0) until Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Randomization to LoAC During the Treatment Period | Time (in days) from randomization to LoAC during the treatment period is the interval from randomization to the occurrence of the LoAC. The LoAC was defined as any 1 of the following during the treatment period: - morning PEF decrease ≥30% from baseline on 2 consecutive days or morning handheld FEV1 decrease ≥20% from baseline on 2 consecutive days; - increase in SABA/quick-relief medication ≥6 puffs over baseline use in 24 hours on 2 consecutive days; increase in ICS dose ≥4 × most recent dose; - systemic corticosteroid use; - asthma ER visit or hospitalization. | From randomization (Week 0) until Week 16 | 
| Change From Baseline in Asthma Control Questionnaire 6-Question Version (ACQ-6) Score at Week 16 | The ACQ-6 is a 6-item validated asthma assessment tool that has been widely used. Six questions are self-assessments (completed by the participant), 5 questions assessing asthma symptoms: night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and 1 question for short-acting bronchodilator use. Each item on the ACQ-6 has a possible score ranges from 0 to 6, and the total score is the mean of all responses. The total score ranging from 0-6 (0=totally controlled and 6=severely uncontrolled). A higher score indicated poorer asthma control. | Baseline, Week 16 | 
| Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second (FEV1) at Week 16 | FEV1 (measured by handheld spirometer) is the volume of air that can be forcibly exhaled from the lungs in the first second. The percent predicted FEV1 equals the participant's observed FEV1 divided by the participant's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100%. | Baseline, Week 16 | 
| Change From Baseline in Daily Average Use of Short-acting Beta-agonist (SABA) Quick Relief Medication at Week 16 | Number of inhalations/puffs of SABA/quick relief inhaler used was recorded in the e-diary daily. | Baseline, Week 16 | 
| Number of Participants Who Had a Clinical Asthma Exacerbation (CAE) During the Treatment Period | The CAEs during the study were defined as a worsening of asthma symptoms resulting in any 1 of the following: - the use of systemic corticosteroids (oral or injectable); - an emergency department visit due to asthma treated with systemic corticosteroids; - an inpatient hospitalization due to asthma. Worsening asthma included new or increased symptoms or signs that either worried the participant or were related to an asthma-specific alert (if available through the e-diary/handheld spirometer). | From randomization (Week 0) until Week 16 | 
| Time From Randomization to First CAE During the Treatment Period for Participants With CAE | The CAEs during the study were defined as a worsening of asthma symptoms resulting in any 1 of the following: - the use of systemic corticosteroids (oral or injectable); - an emergency department visit due to asthma treated with systemic corticosteroids; - an inpatient hospitalization due to asthma. Worsening asthma included new or increased symptoms or signs that either worried the participant or were related to an asthma-specific alert (if available through the e-diary/handheld spirometer). | From randomization (Week 0) until Week 16 | 
| Change From Baseline in Number of Nighttime Awakenings Due to Asthma at Week 16 | Participants recorded the number of nighttime awakenings due to asthma in the e-diary daily, in the morning. | Baseline, Week 16 | 
| Percent Change in ICS Dose During the Treatment Period | The ICS dose was not collected in the participant diary as planned. | From randomization (Week 0) until Week 16 | 
| Change From Baseline in Forced Vital Capacity (FVC) at Week 16 | FVC (measured by handheld spirometer) is the volume of air that can be forcibly and completely blown out after full inspiration, measured in liters. | Baseline, Week 16 | 
| Change From Baseline in Forced Expiratory Flow at 25-75% of Pulmonary Volume (FEF25%-75%) at Week 16 | The FEF25%-75% (measured by handheld spirometer) is the forced expiratory flow from 25% to 75% of FVC | Baseline, Week 16 | 
| Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 16 | FeNO was performed prior to the on-site spirometry. | Baseline, Week 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Serious adverse events (SAEs) included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered treatment emergent (TEAEs) if onset occurred on or after the first dose date. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. AEs include clinically significant changes from baseline in any one of the following categories: clinical laboratory test results, vital signs, ECG findings. | From randomization (Week 0) until Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
T2 low, non-T2 asthma