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

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

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.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: TEV-48574

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Kozloduy, Bulgaria, 999999
    • Teva Investigational Site 59159
  • Montana, Bulgaria, 3400
    • Teva Investigational Site 59166
  • Plovdiv, Bulgaria, 4002
    • Teva Investigational Site 59163
  • Plovdiv, Bulgaria, 4003
    • Teva Investigational Site 59189
  • Plovdiv, Bulgaria, 4003
    • Teva Investigational Site 59190
  • Ruse, Bulgaria, 7002
    • Teva Investigational Site 59164
  • Sofia, Bulgaria, 1000
    • Teva Investigational Site 59168
  • Sofia, Bulgaria, 1606
    • Teva Investigational Site 59167
  • Stara Zagora, Bulgaria, 6001
    • Teva Investigational Site 59160
  • Stara Zagora, Bulgaria, 999999
    • Teva Investigational Site 59161
  • Varna, Bulgaria, 9020
    • Teva Investigational Site 59165
  • Veliko Tarnovo, Bulgaria, 5000
    • Teva Investigational Site 59162
  • Vratsa, Bulgaria, 3001
    • Teva Investigational Site 59192
• Czechia
  • Brandys nad Labem, Czechia, 25001
    • Teva Investigational Site 54197
  • Jindrichuv Hradec, Czechia, 999999
    • Teva Investigational Site 54194
  • Miroslav, Czechia, 671 721
    • Teva Investigational Site 54193
  • Prague 8, Czechia, 182 00
    • Teva Investigational Site 54195
  • Strakonice, Czechia, 999999
    • Teva Investigational Site 54203
  • Teplice, Czechia, 415 01
    • Teva Investigational Site 54196
• Germany
  • Berlin, Germany, 10787
    • Teva Investigational Site 32747
  • Frankfurt am Main, Germany, 60596
    • Teva Investigational Site 32741
  • Frankfurt/Main, Germany, 60389
    • Teva Investigational Site 32759
  • Geesthacht, Germany, 21502
    • Teva Investigational Site 32744
  • Hamburg, Germany, 22299
    • Teva Investigational Site 32739
  • Hannover, Germany, 30173
    • Teva Investigational Site 32746
  • Leipzig, Germany, 04537
    • Teva Investigational Site 32757
  • Leipzig, Germany, 4157
    • Teva Investigational Site 32758
  • Leipzig, Germany, ?04275
    • Teva Investigational Site 32756
  • Luebeck, Germany, 23552
    • Teva Investigational Site 32742
  • Muenchen, Germany, 81241
    • Teva Investigational Site 32743
  • Rheine, Germany, 48431
    • Teva Investigational Site 32745
• Poland
  • Bydgoszcz, Poland, 85-231
    • Teva Investigational Site 53461
  • Krakaw, Poland, 31-033
    • Teva Investigational Site 53458
  • Krakow, Poland, 31-559
    • Teva Investigational Site 53457
  • Lodz, Poland, 90-302
    • Teva Investigational Site 53455
  • Poznan, Poland, 60 - 823
    • Teva Investigational Site 53483
  • Poznan, Poland, 60-214
    • Teva Investigational Site 53459
  • Sucha Beskidzka, Poland, 34200
    • Teva Investigational Site 53486
  • Tarnow, Poland, 33-100
    • Teva Investigational Site 53462
  • Warszawa, Poland, 01-868
    • Teva Investigational Site 53485
  • Wroclaw, Poland, 53-201
    • Teva Investigational Site 53460
  • Wroclaw, Poland, 53-301
    • Teva Investigational Site 53456
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Teva Investigational Site 14884
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Teva Investigational Site 14915
  • California
    • Bakersfield, California, United States, 93301
      • Teva Investigational Site 14914
    • Huntington Beach, California, United States, 92647
      • Teva Investigational Site 15234
    • Los Angeles, California, United States, 90025
      • Teva Investigational Site 14896
    • Los Angeles, California, United States, 90025
      • Teva Investigational Site 14918
    • Los Angeles, California, United States, 90048
      • Teva Investigational Site 14913
    • Rolling Hills Estates, California, United States, 90274-7604
      • Teva Investigational Site 14910
    • San Diego, California, United States, 92123
      • Teva Investigational Site 14907
    • San Jose, California, United States, 95117
      • Teva Investigational Site 14891
    • Stockton, California, United States, 95207
      • Teva Investigational Site 15231
    • Walnut Creek, California, United States, 94598
      • Teva Investigational Site 14916
    • Westminster, California, United States, 92683
      • Teva Investigational Site 14878
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Teva Investigational Site 14895
    • Denver, Colorado, United States, 80246
      • Teva Investigational Site 14917
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Teva Investigational Site 15222
    • Cutler Bay, Florida, United States, 33189
      • Teva Investigational Site 15223
    • Hialeah, Florida, United States, 33012
      • Teva Investigational Site 14911
    • Hialeah, Florida, United States, 33015
      • Teva Investigational Site 15225
    • Miami, Florida, United States, 33134
      • Teva Investigational Site 14900
    • Miami, Florida, United States, 33173
      • Teva Investigational Site 14883
    • Panama City, Florida, United States, 32405
      • Teva Investigational Site 14908
    • Tallahassee, Florida, United States, 32308-4355
      • Teva Investigational Site 14894
    • Tampa, Florida, United States, 33607
      • Teva Investigational Site 15224
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Teva Investigational Site 14924
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Teva Investigational Site 14897
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Teva Investigational Site 15220
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747-3322
      • Teva Investigational Site 14877
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Teva Investigational Site 14922
    • Saint Louis, Missouri, United States, 63141
      • Teva Investigational Site 14893
  • Montana
    • Missoula, Montana, United States, 59808
      • Teva Investigational Site 14904
  • Nebraska
    • Bellevue, Nebraska, United States, 68123-4303
      • Teva Investigational Site 14912
    • Lincoln, Nebraska, United States, 68505-2343
      • Teva Investigational Site 14903
  • New Jersey
    • Skillman, New Jersey, United States, 08558
      • Teva Investigational Site 15227
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Teva Investigational Site 15221
    • Monroe, North Carolina, United States, 28112
      • Teva Investigational Site 15226
    • Raleigh, North Carolina, United States, 27607
      • Teva Investigational Site 14882
    • Wilmington, North Carolina, United States, 28401
      • Teva Investigational Site 14887
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Teva Investigational Site 14889
    • Dublin, Ohio, United States, 43016
      • Teva Investigational Site 14886
    • Toledo, Ohio, United States, 43617
      • Teva Investigational Site 14901
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Teva Investigational Site 14888
    • Oklahoma City, Oklahoma, United States, 73112-4432
      • Teva Investigational Site 14880
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Teva Investigational Site 14923
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Teva Investigational Site 14890
  • Texas
    • Allen, Texas, United States, 75013
      • Teva Investigational Site 14925
    • Austin, Texas, United States, 78759
      • Teva Investigational Site 15230
    • Dallas, Texas, United States, 75231
      • Teva Investigational Site 14909
    • El Paso, Texas, United States, 79903-3508
      • Teva Investigational Site 14902
    • Fort Worth, Texas, United States, 76244
      • Teva Investigational Site 14919
    • Houston, Texas, United States, 77030
      • Teva Investigational Site 14921
    • McKinney, Texas, United States, 75069
      • Teva Investigational Site 14905
    • San Antonio, Texas, United States, 78229
      • Teva Investigational Site 14879
  • Washington
    • Spokane, Washington, United States, 99204
      • Teva Investigational Site 14920
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Teva Investigational Site 14881

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo matching to TEV-48574 SC every 2 weeks for a total of 8 doses.	Drug: Placebo; Matching Placebo
Experimental: TEV-48574; 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; subcutaneous infusion

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

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2020
• Primary Completion (Actual): January 17, 2022
• Study Completion (Actual): January 17, 2022

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: September 3, 2020
• First Posted (Actual): September 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: T2 low, non-T2 asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: TV48574-AS-20031; 2020-001927-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No