Asthma
Conditions
Keywords
T2 low, non-T2 asthma
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.
Interventions
DRUGTEV-48574
subcutaneous infusion
DRUGPlacebo
Matching Placebo
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Loss of Asthma Control (LoAC) During the Treatment Period | From randomization (Week 0) until Week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Asthma Control Questionnaire 6-Question Version (ACQ-6) Score at Week 16 | Baseline, 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. |
| Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second (FEV1) at Week 16 | Baseline, 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%. |
| Change From Baseline in Daily Average Use of Short-acting Beta-agonist (SABA) Quick Relief Medication at Week 16 | Baseline, Week 16 | Number of inhalations/puffs of SABA/quick relief inhaler used was recorded in the e-diary daily. |
| Number of Participants Who Had a Clinical Asthma Exacerbation (CAE) During the Treatment Period | From randomization (Week 0) until Week 16 | 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). |
| Time From Randomization to First CAE During the Treatment Period for Participants With CAE | From randomization (Week 0) until Week 16 | 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). |
| Time From Randomization to LoAC During the Treatment Period | From randomization (Week 0) until Week 16 | 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. |
| Percent Change in ICS Dose During the Treatment Period | From randomization (Week 0) until Week 16 | The ICS dose was not collected in the participant diary as planned. |
| Change From Baseline in Forced Vital Capacity (FVC) at Week 16 | Baseline, 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. |
| Change From Baseline in Forced Expiratory Flow at 25-75% of Pulmonary Volume (FEF25%-75%) at Week 16 | Baseline, Week 16 | The FEF25%-75% (measured by handheld spirometer) is the forced expiratory flow from 25% to 75% of FVC |
| Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 16 | Baseline, Week 16 | FeNO was performed prior to the on-site spirometry. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From randomization (Week 0) until Week 24 | 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. |
| Change From Baseline in Number of Nighttime Awakenings Due to Asthma at Week 16 | Baseline, Week 16 | Participants recorded the number of nighttime awakenings due to asthma in the e-diary daily, in the morning. |
Countries
Bulgaria, Czechia, Germany, Poland, United States
Participant flow
Pre-assignment details
A total of 65 participants were randomly assigned to treatment (33 participants in the TEV-48574 group and 32 participants in the placebo group). Of these, 64 participants received at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses. | 32 |
| TEV-48574 Participants received TEV-48574 loading dose SC on the day of randomization and the subsequent corresponding TEV-48574 maintenance doses SC every 2 weeks for a total of 8 doses (1 loading dose and 7 maintenance doses). | 33 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Loss of asthma control (LoAC) | 0 | 1 |
| Overall Study | Other than specified | 1 | 0 |
| Overall Study | Sponsor decision | 2 | 2 |
| Overall Study | Study termination | 10 | 10 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | TEV-48574 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 12.38 | 57.6 years STANDARD_DEVIATION 13.23 | 56.3 years STANDARD_DEVIATION 14.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 11 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 54 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 6 Participants | 10 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 26 Participants | 54 Participants | 28 Participants |
| Sex: Female, Male Female | 22 Participants | 41 Participants | 19 Participants |
| Sex: Female, Male Male | 11 Participants | 24 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 33 |
| other Total, other adverse events | 4 / 31 | 6 / 33 |
| serious Total, serious adverse events | 1 / 31 | 1 / 33 |
Outcome results
Primary
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.
Time frame: From randomization (Week 0) until Week 16
Population: The ITT analysis set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Experienced Loss of Asthma Control (LoAC) During the Treatment Period | 13 Participants |
| TEV-48574 | Number of Participants Who Experienced Loss of Asthma Control (LoAC) During the Treatment Period | 17 Participants |
Comparison: Analysis was performed using logistic regression with fixed effects for treatment, baseline FEV1, weight, age group, and gender.p-value: 0.781795% CI: [0.545, 4.071]Regression, Logistic
Secondary
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.
Time frame: Baseline, Week 16
Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Control Questionnaire 6-Question Version (ACQ-6) Score at Week 16 | -0.560 units on a scale | Standard Deviation 0.4546 |
| TEV-48574 | Change From Baseline in Asthma Control Questionnaire 6-Question Version (ACQ-6) Score at Week 16 | -0.833 units on a scale | Standard Deviation 0.725 |
Secondary
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.
Time frame: Baseline, Week 16
Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Daily Average Use of Short-acting Beta-agonist (SABA) Quick Relief Medication at Week 16 | -0.235 puffs of SABA/day | Standard Deviation 1.2641 |
| TEV-48574 | Change From Baseline in Daily Average Use of Short-acting Beta-agonist (SABA) Quick Relief Medication at Week 16 | -0.305 puffs of SABA/day | Standard Deviation 1.6501 |
Secondary
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
Time frame: Baseline, Week 16
Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Flow at 25-75% of Pulmonary Volume (FEF25%-75%) at Week 16 | -0.026 liters/second | Standard Deviation 0.2451 |
| TEV-48574 | Change From Baseline in Forced Expiratory Flow at 25-75% of Pulmonary Volume (FEF25%-75%) at Week 16 | 0.166 liters/second | Standard Deviation 0.4342 |
Secondary
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.
Time frame: Baseline, Week 16
Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 16 | 0.014 liters | Standard Deviation 0.3052 |
| TEV-48574 | Change From Baseline in Forced Vital Capacity (FVC) at Week 16 | 0.155 liters | Standard Deviation 0.3964 |
Secondary
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 16
FeNO was performed prior to the on-site spirometry.
Time frame: Baseline, Week 16
Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 16 | 5.364 parts per billion (ppb) | Standard Deviation 6.9609 |
| TEV-48574 | Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 16 | 10.375 parts per billion (ppb) | Standard Deviation 12.585 |
Secondary
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.
Time frame: Baseline, Week 16
Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Number of Nighttime Awakenings Due to Asthma at Week 16 | -1.224 nighttime awakenings | Standard Deviation 2.0182 |
| TEV-48574 | Change From Baseline in Number of Nighttime Awakenings Due to Asthma at Week 16 | -0.208 nighttime awakenings | Standard Deviation 2.7274 |
Secondary
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%.
Time frame: Baseline, Week 16
Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second (FEV1) at Week 16 | 0.121 %predicted FEV1 | Standard Deviation 8.3126 |
| TEV-48574 | Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second (FEV1) at Week 16 | 4.844 %predicted FEV1 | Standard Deviation 12.4343 |
Secondary
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).
Time frame: From randomization (Week 0) until Week 16
Population: The ITT analysis set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Had a Clinical Asthma Exacerbation (CAE) During the Treatment Period | 2 Participants |
| TEV-48574 | Number of Participants Who Had a Clinical Asthma Exacerbation (CAE) During the Treatment Period | 3 Participants |
Secondary
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.
Time frame: From randomization (Week 0) until Week 24
Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 14 Participants |
| TEV-48574 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 18 Participants |
Secondary
Percent Change in ICS Dose During the Treatment Period
The ICS dose was not collected in the participant diary as planned.
Time frame: From randomization (Week 0) until Week 16
Population: Due to change in planned analysis, no data was collected to evaluate this outcome measure.
Secondary
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).
Time frame: From randomization (Week 0) until Week 16
Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time From Randomization to First CAE During the Treatment Period for Participants With CAE | 46.5 days |
| TEV-48574 | Time From Randomization to First CAE During the Treatment Period for Participants With CAE | 37.0 days |
Secondary
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.
Time frame: From randomization (Week 0) until Week 16
Population: The ITT analysis set included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time From Randomization to LoAC During the Treatment Period | NA days |
| TEV-48574 | Time From Randomization to LoAC During the Treatment Period | 109.0 days |