Trial Outcomes & Findings for A Study to Test if TEV-48574 is Effective in Relieving Asthma (NCT NCT04545385)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

From randomization (Week 0) until Week 16

Results posted on

2023-03-13

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to TEV-48574 subcutaneously (SC) every 2 weeks for a total of 8 doses.	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).
Overall Study STARTED	32	33
Overall Study Received at Least 1 Dose of Study Drug	31	33
Overall Study COMPLETED	17	20
Overall Study NOT COMPLETED	15	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to TEV-48574 subcutaneously (SC) every 2 weeks for a total of 8 doses.	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).
Overall Study Withdrawal by Subject	2	0
Overall Study Loss of asthma control (LoAC)	0	1
Overall Study Study termination	10	10
Overall Study Sponsor decision	2	2
Overall Study Other than specified	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=32 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=33 Participants 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).	Total n=65 Participants Total of all reporting groups
Age, Continuous	56.3 years STANDARD_DEVIATION 14.14 • n=5 Participants	58.8 years STANDARD_DEVIATION 12.38 • n=7 Participants	57.6 years STANDARD_DEVIATION 13.23 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	28 Participants n=5 Participants	26 Participants n=7 Participants	54 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization (Week 0) until Week 16

Population: The ITT analysis set included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=33 Participants 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).
Number of Participants Who Experienced Loss of Asthma Control (LoAC) During the Treatment Period	13 Participants	17 Participants

SECONDARY outcome

Timeframe: From randomization (Week 0) until Week 16

Population: The ITT analysis set included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=33 Participants 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).
Time From Randomization to LoAC During the Treatment Period	NA days Interval 60.0 to Due to smaller number of participants with an event, median and upper limit of 95% confidence interval (CI) could not be calculated.	109.0 days Interval 45.0 to Due to smaller number of participants with an event, upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=16 Participants 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).
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	-0.833 units on a scale Standard Deviation 0.7250

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

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%.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=16 Participants 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).
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	4.844 %predicted FEV1 Standard Deviation 12.4343

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Number of inhalations/puffs of SABA/quick relief inhaler used was recorded in the e-diary daily.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=16 Participants 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).
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	-0.305 puffs of SABA/day Standard Deviation 1.6501

SECONDARY outcome

Timeframe: From randomization (Week 0) until Week 16

Population: The ITT analysis set included all randomized participants.

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).

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=33 Participants 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).
Number of Participants Who Had a Clinical Asthma Exacerbation (CAE) During the Treatment Period	2 Participants	3 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=3 Participants 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).
Time From Randomization to First CAE During the Treatment Period for Participants With CAE	46.5 days Interval 38.0 to 55.0	37.0 days Interval 30.0 to 54.0

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Participants recorded the number of nighttime awakenings due to asthma in the e-diary daily, in the morning.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=16 Participants 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).
Change From Baseline in Number of Nighttime Awakenings Due to Asthma at Week 16	-1.224 nighttime awakenings Standard Deviation 2.0182	-0.208 nighttime awakenings Standard Deviation 2.7274

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

TEV-48574

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=31 participants at risk Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=33 participants at risk 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).
Reproductive system and breast disorders Vaginal prolapse	3.2% 1/31 • Number of events 1 • From randomization (Week 0) until Week 24 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/33 • From randomization (Week 0) until Week 24 Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertensive crisis	0.00% 0/31 • From randomization (Week 0) until Week 24 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	3.0% 1/33 • Number of events 1 • From randomization (Week 0) until Week 24 Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	Placebo n=31 participants at risk Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	TEV-48574 n=33 participants at risk 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).
Infections and infestations Nasopharyngitis	9.7% 3/31 • Number of events 3 • From randomization (Week 0) until Week 24 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	9.1% 3/33 • Number of events 3 • From randomization (Week 0) until Week 24 Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	6.5% 2/31 • Number of events 2 • From randomization (Week 0) until Week 24 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	9.1% 3/33 • Number of events 3 • From randomization (Week 0) until Week 24 Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER