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

• ClinicalTrials.gov Identifier: NCT04545385
• Recruitment Status: Terminated
• First Posted: September 11, 2020
• Results First Posted: March 13, 2023
• Last Update Posted: March 13, 2023
• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Information provided by (Responsible Party): Teva Branded Pharmaceutical Products R&D, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Asthma
• Interventions: Drug: TEV-48574; Drug: Placebo
• Enrollment: 65

Participant Flow

Recruitment Details
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.

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description	Participants received placebo matched to TEV-48574 subcutaneously (SC) every 2 weeks for a total of 8 doses.	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).
Period Title: Overall Study
Started	32	33
Received at Least 1 Dose of Study Drug	31	33
Completed	17	20
Not Completed	15	13
Reason Not Completed
Withdrawal by Subject	2	0
Loss of asthma control (LoAC)	0	1
Study termination	10	10
Sponsor decision	2	2
Other than specified	1	0

Baseline Characteristics

Arm/Group Title		Placebo	TEV-48574	Total
Arm/Group Description		Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 of all reporting groups
Overall Number of Baseline Participants		32	33	65
Baseline Analysis Population Description		The intent-to-treat (ITT) analysis set included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	32 participants	33 participants	65 participants
		56.3 (14.14)	58.8 (12.38)	57.6 (13.23)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	33 participants	65 participants
	Female	19 59.4%	22 66.7%	41 63.1%
	Male	13 40.6%	11 33.3%	24 36.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	33 participants	65 participants
	Hispanic or Latino	5 15.6%	6 18.2%	11 16.9%
	Not Hispanic or Latino	27 84.4%	27 81.8%	54 83.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	32 participants	33 participants	65 participants
	White	28 87.5%	26 78.8%	54 83.1%
	Black or African American	4 12.5%	6 18.2%	10 15.4%
	Other	0 0.0%	1 3.0%	1 1.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced Loss of Asthma Control (LoAC) During the Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	32	33
Measure Type: Count of Participants; Unit of Measure: Participants
	13 40.6%	17 51.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, TEV-48574
	Comments	Analysis was performed using logistic regression with fixed effects for treatment, baseline FEV1, weight, age group, and gender.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7817
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95%; 0.545 to 4.071
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Time From Randomization to LoAC During the Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	32	33
Median (95% Confidence Interval); Unit of Measure: days
	NA [1]; (60.0 to NA)	109.0 [2]; (45.0 to NA)

[1]

Due to smaller number of participants with an event, median and upper limit of 95% confidence interval (CI) could not be calculated.

[2]

Due to smaller number of participants with an event, upper limit of 95% CI could not be calculated.

3. Secondary Outcome

Title	Change From Baseline in Asthma Control Questionnaire 6-Question Version (ACQ-6) Score at Week 16
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	11	16
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.560 (0.4546)	-0.833 (0.7250)

4. Secondary Outcome

Title	Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second (FEV1) at Week 16
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	11	16
Mean (Standard Deviation); Unit of Measure: %predicted FEV1
	0.121 (8.3126)	4.844 (12.4343)

5. Secondary Outcome

Title	Change From Baseline in Daily Average Use of Short-acting Beta-agonist (SABA) Quick Relief Medication at Week 16
Description	Number of inhalations/puffs of SABA/quick relief inhaler used was recorded in the e-diary daily.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	11	16
Mean (Standard Deviation); Unit of Measure: puffs of SABA/day
	-0.235 (1.2641)	-0.305 (1.6501)

6. Secondary Outcome

Title	Number of Participants Who Had a Clinical Asthma Exacerbation (CAE) During the Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	32	33
Measure Type: Count of Participants; Unit of Measure: Participants
	2 6.3%	3 9.1%

7. Secondary Outcome

Title	Time From Randomization to First CAE During the Treatment Period for Participants With CAE
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	2	3
Median (Full Range); Unit of Measure: days
	46.5; (38 to 55)	37.0; (30 to 54)

8. Secondary Outcome

Title	Change From Baseline in Number of Nighttime Awakenings Due to Asthma at Week 16
Description	Participants recorded the number of nighttime awakenings due to asthma in the e-diary daily, in the morning.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	11	16
Mean (Standard Deviation); Unit of Measure: nighttime awakenings
	-1.224 (2.0182)	-0.208 (2.7274)

9. Secondary Outcome

Title	Percent Change in ICS Dose During the Treatment Period
Description	The ICS dose was not collected in the participant diary as planned.
Time Frame	From randomization (Week 0) until Week 16

Outcome Measure Data

Analysis Population Description

Due to change in planned analysis, no data was collected to evaluate this outcome measure.

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

10. Secondary Outcome

Title	Change From Baseline in Forced Vital Capacity (FVC) at Week 16
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	11	16
Mean (Standard Deviation); Unit of Measure: liters
	0.014 (0.3052)	0.155 (0.3964)

11. Secondary Outcome

Title	Change From Baseline in Forced Expiratory Flow at 25-75% of Pulmonary Volume (FEF25%-75%) at Week 16
Description	The FEF25%-75% (measured by handheld spirometer) is the forced expiratory flow from 25% to 75% of FVC
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	11	16
Mean (Standard Deviation); Unit of Measure: liters/second
	-0.026 (0.2451)	0.166 (0.4342)

12. Secondary Outcome

Title	Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 16
Description	FeNO was performed prior to the on-site spirometry.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	11	16
Mean (Standard Deviation); Unit of Measure: parts per billion (ppb)
	5.364 (6.9609)	10.375 (12.5850)

13. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	TEV-48574
Arm/Group Description:	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.	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 Number of Participants Analyzed	31	33
Measure Type: Count of Participants; Unit of Measure: Participants
	14 45.2%	18 54.5%

Adverse Events

Time Frame	From randomization (Week 0) until Week 24
Adverse Event Reporting Description	Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title	Placebo		TEV-48574
Arm/Group Description	Participants received placebo matched to TEV-48574 SC every 2 weeks for a total of 8 doses.		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).
All-Cause Mortality
	Placebo		TEV-48574
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/31 (0.00%)		0/33 (0.00%)
Serious Adverse Events
	Placebo		TEV-48574
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/31 (3.23%)		1/33 (3.03%)
Reproductive system and breast disorders
Vaginal prolapse † 1	1/31 (3.23%)	1	0/33 (0.00%)	0
Vascular disorders
Hypertensive crisis † 1	0/31 (0.00%)	0	1/33 (3.03%)	1
1 Term from vocabulary, MedDRA 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		TEV-48574
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/31 (12.90%)		6/33 (18.18%)
Infections and infestations
Nasopharyngitis † 1	3/31 (9.68%)	3	3/33 (9.09%)	3
Nervous system disorders
Headache † 1	2/31 (6.45%)	2	3/33 (9.09%)	3
1 Term from vocabulary, MedDRA 24.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.
• Phone: 888-483-8279
• EMail: USMedInfo@tevapharm.com

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT04545385
• Other Study ID Numbers: TV48574-AS-20031; 2020-001927-15 ( EudraCT Number )
• First Submitted: August 24, 2020
• First Posted: September 11, 2020
• Results First Submitted: December 15, 2022
• Results First Posted: March 13, 2023
• Last Update Posted: March 13, 2023