A Study to Test if TEV-53275 is Effective in Relieving Asthma

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the efficacy of TEV-53275 administered subcutaneously (sc) in adult participants with persistent asthma and an eosinophilic phenotype compared to placebo. A secondary objective is to evaluate the efficacy of TEV-53275 compared to placebo assessed by lung function, asthma symptoms, rescue medication use, and quality of life measures. Another secondary objective is to evaluate the safety and tolerability of TEV-53275 administered sc in adult participants with persistent asthma and an eosinophilic phenotype compared with placebo, and lastly, to evaluate the immunogenicity of TEV-53275 administered sc in adult participants with persistent asthma and an eosinophilic phenotype.

Detailed Description
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The planned study duration is approximately 16 months. The total duration of study participation is approximately 34 weeks including up to a 2-week screening period, a 2-week run-in period, a 16-week treatment period, and a follow-up visit 14 weeks after the final treatment visit.

Official Title
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A Phase 2, Multicenter, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Assess the Safety, Efficacy and Pharmacodynamics of TEV 53275 Administered Subcutaneously in Adult Patients With Persistent Eosinophilic Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: TEV-53275 Dose A
* Drug: TEV-53275 Dose B
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is an adult female or male ≥18 years of age. Note: Age requirements are as specified or allowed by local regulations. The participant has a diagnosis of asthma for at least 6 months and has been stable without exacerbation or change in medications for at least 1 month.. Current Asthma Therapy: The participant has been maintained for at least 1 month on stable doses of: medium or high dose inhaled corticosteroids (ICS)±another controller. any fixed dose combination ICS (low, medium, or high) with long-acting beta agonist (LABA)±another controller. Women of non-childbearing potential, or congenitally sterile, or 1-year postmenopausal. Women of childbearing potential must have a negative β-human chorionic gonadotropin (β-HCG) test result and practice a highly effective method of birth control prior to investigational medicinal product (IMP) administration and 30 weeks after the dose of IMP. The participant, as judged by the investigator, is able to continue their current asthma maintenance medications throughout the study. NOTE- Additional criteria apply, please contact the investigator for more information. Exclusion Criteria: Life threatening asthma, defined as a history of asthma episode(s) requiring intubation and/or associated hypercapnea, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s). The participant has a suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that has not resolved at least 2 weeks before the screening period. Note: Participants who develop an upper respiratory infection/lower respiratory infection (URI/LRI) during the run-in period may rescreen 2 weeks after symptoms resolve and undergo coronavirus disease 2019 (COVID-19) testing. Participants with a confirmed infection with COVID-19 within 3 months prior to the screening visit. The participant has an eosinophilic condition including hypereosinophilic syndrome, eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis (EGPA [Churg Strauss syndrome]), or allergic bronchopulmonary aspergillosis. The participant has an active helminthic or parasitic infection currently or within the last 6 months. The participant has a history of malignancy other than fully resected basal cell carcinoma of the skin. The participant has any clinically significant, uncontrolled medical or psychiatric condition (treated or untreated) that would interfere with the study schedule or procedures, interpretation of efficacy results, or compromise the participant's safety. The participant has known history of, or a positive test result for, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Ab), or human immunodeficiency virus (HIV) Types 1 or 2 Ab (according to 4th generation serology testing). The participant is a pregnant or lactating woman, or plans to become pregnant during the study. The participant has previously participated in a study with TEV-53275. The participant has participated in another study of an IMP (or a medical device) within the previous 30 days or is currently participating in another study of an IMP (or a medical device). The participant has been treated with a monoclonal antibody used to treat asthma or other inflammatory conditions within the washout period (5 half-lives), has demonstrated hypersensitivity or anaphylaxis to a monoclonal antibody (Appendix G),or is currently using or has used a systemic immunosuppressive medication within the last 6 months. NOTE: Prior depemokimab exposure is prohibited without exception. The participant has a history of chronic alcohol or drug abuse within the previous 2 years. The participant currently smokes or has a smoking history of 10 pack years or more (a pack year is defined as smoking 1 pack of cigarettes [20 cigarettes]/day for 1 year), OR the participant used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco), OR the participant has smoked marijuana within 1 month, OR the participant has a history of vaping tobacco, marijuana, or any other substance within 24 months. Vulnerable participants (eg, people kept in detention). NOTE- Additional criteria apply, please contact the investigator for more information

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEV-53275 Dose A<br> | Drug: TEV-53275 Dose A<br>* subcutaneous (sc) injection<br>|
| Experimental: TEV-53275 Dose B<br> | Drug: TEV-53275 Dose B<br>* subcutaneous (sc) injection<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching subcutaneous (sc) placebo injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinic-based Standardized Baseline-adjusted Morning Trough (Pre-bronchodilator) FEV1 at Week 12 | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Least square (LS) mean and standard error (SE) were calculated using a mixed model for repeated measures (MMRM). | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Well-controlled Asthma Status (Yes Versus No) at Weeks 12 and 16 | The weekly asthma control status (Yes or No) is the derived asthma control composite score based on the following criteria: 1. Two or more of the following criteria were fulfilled: ≤2 days with a daily asthma symptom score >1; - ≤2 days of albuterol/salbutamol used as rescue medication up to a maximum of 4 occasions per week (multiple occasions per day are counted as separate occasions); - morning FEV1 ≥80% predicted for each day (by handheld device) and 2. Both of the following criteria were fulfilled: no night-time awakenings due to asthma; - no use of asthma maintenance medications. The asthma control status in each weekly analysis window was Yes if the conditions 1 and 2 above were met, No otherwise. | Weeks 12 and 16 | 
| Change From Baseline in the Weekly Average of Daily Morning Trough (Pre-Rescue Bronchodilator) FEV1 Over 12 Weeks From Week 1 Through 12 and Over 16 Weeks From Week 1 Through 16 | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by a handheld device. The post-baseline analysis window for over 12 weeks was from the first day of study drug up to Day 84. The post-baseline analysis window for over 16 weeks was from the first day of study drug up to Day 112. The daily average of the efficacy data with each weekly analysis window was calculated based on non-missing e-diary as follow: Summation of FEV1 during an analysis window/Number of days with nonmissing data in the analysis window. LS mean and SE was calculated using an MMRM. | Baseline, up to Week 12, up to Week 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, 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 participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through the end of the study. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | Baseline up to Week 30 | 
| Number of Participants Who Received at Least 1 Concomitant Asthma Medication | Concomitant asthma medications included Antihistamines for systemic use (Cetirizine); Corticosteroids for systemic use (Prednisone, Methylprednisolone); and Drugs for obstructive airway diseases (Salbutamol, Fluticasone etc.). | Baseline up to Week 30 | 
| Number of Participants Developing Antidrug Antibodies (ADAs) Throughout the Study | A participant was classified as having a treatment-emergent ADA response if either of the following were true: - The participant had a positive sample at any of the postdose time points, but not at the predose (baseline) time point; - The participant had a positive sample at predose (baseline) and 1 or more postdose time points, but the titer of a postdose sample(s) was increased by at least 4-fold when comparing it to that of the predose sample. | Baseline up to Week 30 | 
| Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Serum Chemistry Value | Potentially clinically significant serum chemistry abnormalities included: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase, Gamma-glutamyl transpeptidase (GGT), Lactate dehydrogenase (LDH), and Creatinine phosphokinase each ≥3 * upper limit of normal (ULN); Blood urea nitrogen ≥10.71 millimoles (mmol)/liter (L); Creatinine ≥177 micromoles (μmol)/L; and Bilirubin (total) ≥34.2 μmol /L. | Baseline up to Week 30 | 
| Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Hematology Value | Potentially clinically significant hematological abnormalities included: White blood cells (WBCs) count ≤3.0 *10^9 cells/L or ≥20 * 10^9 cells/L; Hemoglobin ≤95 grams (g)/L in females and ≤115 g/L in males; Hematocrit <0.32 L/L in females and <0.37 L/L in males; Platelet count ≤75 * 10^9 cells/L or ≥700 * 10^9 cells/L; and Absolute neutrophil count (ANC) ≤1 * 10^9 cells/L. | Baseline up to Week 30 | 
| Number of Participants With at Least 1 Potentially Clinically Significant Urinalysis Abnormalities | Potentially clinically significant urinalysis abnormalities included: ≥2 unit increase from baseline in urine hemoglobin, ketones, glucose, and total protein. | Baseline up to Week 30 | 
| Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Vital Signs Value | Potentially clinically significant vital signs abnormalities included: Systolic blood pressure (BP): ≤90 millimeters of mercury (mmHg) and decrease from baseline of 20 mm Hg or ≥180 mm Hg and increase from baseline of ≥20 mm Hg; Diastolic BP: ≥105 mmHg and increase from baseline of ≥15 mmHg or ≤50 mmHg and decrease from baseline of ≥15 mmHg; Pulse ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm or ≤50 bpm and decrease from baseline of ≥15 bpm; Temperature ≥38.3 degrees celsius (ºC) and change from baseline of ≥1.1 ºC; Respiratory rate >24 breaths/min and increase from baseline of ≥10 breaths/min. | Baseline up to Week 30 | 
| Number of Participants With Potentially Clinically Significant Abnormal Electrocardiogram Values | Potentially clinically significant electrocardiogram abnormalities including any one of the following values: QTc interval >450 milliseconds (msec) and QTc interval increases from baseline >30 msec, QTc interval >450 msec and QTc interval increases from baseline >60 msec, QTc interval >500 msec and QTc interval increases from baseline >30 msec, QTc interval >500 msec and QTc interval increases from baseline >60 msec; QRS duration >110 msec and a 25% increase from baseline; and PR interval >200 msec and a 25% increase from baseline. | Baseline up to Week 30 | 
| Number of Participants With Injection Site Reactions | Injection site reactions included erythema, ecchymosis, induration, tenderness, warmth, and swelling. Number of participants with erythema, ecchymosis, and induration were reported in following categories: Absent; 5 millimeters (mm) to ≤50 mm (mild); >50 mm to ≤100 mm (moderate); and >100 mm (severe). Number of participants with tenderness, warmth, and swelling were reported in following categories: Absent; mild; moderate; and severe. | Baseline up to Week 30 | 
| Number of Participants Who Did Not Complete the Study Due to AEs | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Number of participants who did not complete the study due to AEs were reported. | Baseline up to Week 30 | 
| Change From Baseline in Weekly Average of Rescue Medication Use Over 12 Weeks From Week 1 Through 12 and Over 16 Weeks From Week 1 Through 16 | The number of times asthma rescue medication (number of inhalations/puffs) was used was assessed (for example, by reviewing the electronic diary or if required due to missing data in the diary, by site tracking of the inhalation counter on the inhaler). Rescue medication included albuterol sulfate inhalation powder (albuterol eMDPI) or equivalent albuterol/salbutamol. The post-baseline analysis window for over 12 weeks was from the first day of study drug up to Day 84. The post-baseline analysis window for over 16 weeks was from the first day of study drug up to Day 112. The daily average of the efficacy data with each weekly analysis window was calculated based on non-missing e-diary as follow: Summation of rescue medication uses during an analysis window/Number of days with nonmissing data in the analysis window. LS mean and SE were calculated using Wilcoxon rank-sum test stratified on randomization stratification factors. | Baseline, up to Week 12, up to Week 16 | 
| Change From Baseline in Weekly Percentage of Asthma Control Days (No Symptoms and No Rescue Medication Use) Over 12 Weeks From Week 1 Through 12 and Over 16 Weeks From Week 1 Through 16 | An asthma control day was defined as a day on which the participant used 0 puffs of inhaled short-acting β-adrenergic agonist (SABA), had no night-time awakenings, and experienced no asthma exacerbations. The post-baseline analysis window for over 12 weeks was from the first day of study drug up to Day 84. The post-baseline analysis window for over 16 weeks was from the first day of study drug up to Day 112. Percentage of asthma control days in each analysis window was calculated as follow: Summation of asthma control days in an analysis window/Number of days with nonmissing data in the analysis window * 100. | Baseline, up to Week 12, up to Week 16 | 
| Change From Baseline in Clinic-based Standardized Baseline-adjusted Morning Trough (Pre-bronchodilator) FEV1 at Week 16 | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. LS mean and SE were calculated using an MMRM. | Baseline, Week 16 | 
| Number of Participants Who Achieved Clinic-based FEV1 ≥80% Predicted at Weeks 12 and 16 | The percent of predicted FEV1 (the volume of air exhaled in the first second of a forced expiration) was measured by handheld device. | Weeks 12 and 16 | 
| Number of Participants Who Achieved Forced Expiratory Flow at 25% to 75% of Forced Expiratory Volume (FVC) (FEF25-75) ≥70% Predicted at Weeks 12 and 16 | The FVC is the volume of air that can be forcibly blown out after full inspiration. FVC results in this study were presented as the forced expiratory flow at 25% to 75% of FVC. | Weeks 12 and 16 | 
| Change From Baseline in FEF25-75 Over 12 Weeks From Week 1 Through 12 and Over 16 Weeks From Week 1 Through 16 | The FVC is the volume of air that can be forcibly blown out after full inspiration. FVC results in this study were presented as the forced expiratory flow at 25% to 75% of FVC. The post-baseline analysis window for over 12 weeks was from the first day of study drug up to Day 84. The post-baseline analysis window for over 16 weeks was from the first day of study drug up to Day 112. The daily average of the efficacy data with each weekly analysis window was calculated based on non-missing e-diary as follow: Summation of FEF25-75 during an analysis window/Number of days with nonmissing data in the analysis window. LS mean and SE were calculated using an MMRM. | Baseline, up to Week 12, up to Week 16 | 
| Time to First Clinical Asthma Exacerbation (CAE) | The time (days) to the first CAE was the interval from the randomization to the occurrence of the first CAE. A CAE was defined as worsening asthma requiring treatment with a systemic corticosteroid for at least 3 days, emergency room visit resulting in systemic corticosteroid treatment, or 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 electronic diary/handheld spirometer) and required the addition of maintenance medications (other than systemic corticosteroids) to control the participant's asthma symptoms based on the investigator's judgment. | Baseline up to Week 16 | 
| Change From Baseline in Asthma Control Questionnaire (ACQ-6) Score at Weeks 12 and 16 | The ACQ-6 is a validated 6-item 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 has a possible score ranging from 0 (no impairment) to 6 (maximum impairment), and the total score is the mean of all responses. The total score ranging from 0 (totally controlled) to 6 (severely uncontrolled) with higher scores indicating maximum impairment. | Baseline, Week 12, Week 16 | 
| Change From Baseline in Asthma Control Test (ACT) Score at Weeks 12 and 16 | The Asthma Control Test (ACT) is a participant self-administered tool for identifying those with poorly controlled asthma comprising 5 items, with 4-week recall (on symptoms and daily functioning). It assesses the frequency of shortness of breath and general asthma symptoms, the use of rescue medications, the effect of asthma on daily functioning, and the overall self-assessment of asthma control measured on a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled). Total scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score >19 indicates well-controlled asthma. | Baseline, Week 12, Week 16 | 
| Change From Baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ[S]) Overall Score at Weeks 12 and 16 | The AQLQ[S] (participants ≥18 years of age version) was self-administered by participants. The questionnaire is a tool to measure the impact of asthma on a participant's quality of life (physical, emotional, social, and occupational). The aim of the questionnaire is to evaluate the problems that were most troublesome to participants in their day to day lives. The questionnaire contains 32 items with a 2-week recall period and used a 7-point Likert scale (7=not impaired at all to 1=severely impaired). The overall AQLQ score was the mean of the responses to each of the 32 questions and ranged from 1 (severely impaired) to 7 (not impaired at all) with higher scores indicating better quality of life. | Baseline, Week 12, Week 16 | 
| Number of Participants Who Achieved FEV1:FVC Ratio ≥0.80 at Weeks 12 and 16 | FEV1 was the volume of air exhaled in the first second of a forced expiration. FVC is the volume of air that can be forcibly blown out after full inspiration. | Weeks 12 and 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Persistent, Eosinophilic, Asthma