Trial Outcomes & Findings for Efficacy and Safety Study of Reslizumab to Treat Poorly Controlled Asthma (NCT NCT00587288)

NCT ID: NCT00587288

Last Updated: 2016-08-17

Results Overview

The ACQ is a 7 question instrument. Each question has 7 possible answers of 0, 1, 2, 3, 4, 5, and 6. Each increasing value is an indication of poorer asthma control. At protocol specified visits, the participant answered questions 1 to 6, circling the response that best described how that participant was during the past week, on the basis of a daily diary for the week before the visit. At the actual visit, study center personnel reviewed the questions and responses with the participant and determined the response and score for question 7. The overall ACQ score was presented as the mean of these 7 individual scores and was a number between 0 and 6, but not necessarily an integer.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 106 participants
• Primary outcome timeframe: Baseline through End of Therapy (up to 15 weeks)
• Results posted on: 2016-08-17

Participant Flow

Participant milestones

Measure	Reslizumab 3 mg/kg reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Study STARTED	53	53
Overall Study COMPLETED	50	44
Overall Study NOT COMPLETED	3	9

Reasons for withdrawal

Measure	Reslizumab 3 mg/kg reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Overall Study Adverse Event	0	1
Overall Study Lack of Efficacy	2	8
Overall Study Protocol Violation	1	0

Baseline Characteristics

Efficacy and Safety Study of Reslizumab to Treat Poorly Controlled Asthma

Baseline characteristics by cohort

Measure	Reslizumab 3 mg/kg n=53 Participants reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=53 Participants saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Total n=106 Participants Total of all reporting groups
Age, Continuous	44.9 years STANDARD_DEVIATION 13.94 • n=5 Participants	45.8 years STANDARD_DEVIATION 11.74 • n=7 Participants	45.4 years STANDARD_DEVIATION 12.83 • n=5 Participants
Age, Customized 18 to < 45 years	28 participants n=5 Participants	20 participants n=7 Participants	48 participants n=5 Participants
Age, Customized 45 to < 65 years	19 participants n=5 Participants	32 participants n=7 Participants	51 participants n=5 Participants
Age, Customized >/= 65 years	6 participants n=5 Participants	1 participants n=7 Participants	7 participants n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	29 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	24 Participants n=7 Participants	43 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through End of Therapy (up to 15 weeks)

Population: Intent-to-treat (ITT) Analysis Set: all participants who received any amount of randomly assigned study drug.

The ACQ is a 7 question instrument. Each question has 7 possible answers of 0, 1, 2, 3, 4, 5, and 6. Each increasing value is an indication of poorer asthma control. At protocol specified visits, the participant answered questions 1 to 6, circling the response that best described how that participant was during the past week, on the basis of a daily diary for the week before the visit. At the actual visit, study center personnel reviewed the questions and responses with the participant and determined the response and score for question 7. The overall ACQ score was presented as the mean of these 7 individual scores and was a number between 0 and 6, but not necessarily an integer.

Outcome measures

Measure	Reslizumab 3 mg/kg n=53 Participants reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=53 Participants saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Mean Change From Baseline to End of Therapy in Asthma Control Questionnaire (ACQ) Score	-0.7 units on a scale Standard Deviation 1.02	-0.3 units on a scale Standard Deviation 1.01

SECONDARY outcome

Timeframe: Baseline, End of Therapy (up to 15 weeks)

Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug.

Responders were defined as participants achieving at least a 0.5 reduction from baseline to End of Therapy in ACQ score. The ACQ is a 7 question instrument. Each question has 7 possible answers of 0, 1, 2, 3, 4, 5, and 6. Each increasing value is an indication of poorer asthma control. At protocol specified visits, the participant answered questions 1 to 6, circling the response that best described how that participant was during the past week, on the basis of a daily diary for the week before the visit. At the actual visit, study center personnel reviewed the questions and responses with the participant and determined the response and score for question 7. The overall ACQ score was presented as the mean of these 7 individual scores and was a number between 0 and 6, but not necessarily an integer.

Outcome measures

Measure	Reslizumab 3 mg/kg n=53 Participants reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=53 Participants saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Percentage of ACQ Responders at End of Therapy Responder = no	45 percentage of participants	64 percentage of participants
Percentage of ACQ Responders at End of Therapy Responder = yes	55 percentage of participants	36 percentage of participants

SECONDARY outcome

Timeframe: Baseline, End of Therapy (up to 15 weeks)

Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.

The change in FEV1 from baseline to End of Therapy was determined. FEV1 was measured during pulmonary function tests using standard spirometry measurements.

Outcome measures

Measure	Reslizumab 3 mg/kg n=52 Participants reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=52 Participants saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Change From Baseline to End of Therapy in Forced Expiratory Volume in the First Second (FEV1)	0.18 L Standard Deviation 0.372	-0.08 L Standard Deviation 0.413

SECONDARY outcome

Timeframe: Baseline, End of Therapy (up to 15 weeks)

Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.

The change in percent predicted FEV1 from baseline to End of Therapy was calculated from the FEV1 measured during pulmonary function tests using standard spirometry measurements. Each participant's percent predicted FEV1 was calculated by adjusting the FEV1 for age, sex, height and race. The percent predicted FEV1 was then calculated by comparing the predicted FEV1 to the observed FEV1 using the Crapo formula (Crapo et al 1981a, Crapo and Morris 1981b, Crapo et al 1982).

Outcome measures

Measure	Reslizumab 3 mg/kg n=52 Participants reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=52 Participants saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Change From Baseline to End of Therapy in Percent Predicted FEV1	6.2 percent predicted FEV1 Standard Deviation 11.76	-2.4 percent predicted FEV1 Standard Deviation 12.93

SECONDARY outcome

Timeframe: End of Screening or Baseline, End of Therapy (up to 15 weeks)

Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.

Outcome measures

Measure	Reslizumab 3 mg/kg n=38 Participants reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=36 Participants saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Mean Change From Baseline to End of Therapy in Induced Sputum Eosinophil Levels	-82.0 percent change in eosinophil levels Standard Deviation 66.88	45.9 percent change in eosinophil levels Standard Deviation 265.79

SECONDARY outcome

Timeframe: up to 15 weeks

Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug.

A CAE was defined as a 20% or more decrease in forced expiratory volume in 1 second (FEV1, absolute value) from the baseline value, a requirement for emergency treatment of asthma, hospital admission for asthma, or treatment with 3 or more days of oral corticosteroids for asthma worsening.

Outcome measures

Measure	Reslizumab 3 mg/kg n=53 Participants reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=53 Participants saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Percentage of Participants With Clinical Asthma Exacerbations (CAEs)	8 percentage of participants	19 percentage of participants

SECONDARY outcome

Timeframe: From start of study drug through 15 weeks + 30 days

Population: ITT Analysis Set: all participants who received any amount of randomly assigned study drug with an assessment at Baseline and End of Therapy.

Participants may have been included in more than 1 category. AEs summarized were those that began or worsened after dispensation of the study drug and before 30 days after the last dose of study drug. If the severity of an AE was missing, the AE was reported as "severe." If drug relationship of an AE was missing, the AE was reported as "probably related." WFT=withdrawn from treatment.

Outcome measures

Measure	Reslizumab 3 mg/kg n=53 Participants reslizumab 3 mg/kg intravenous (IV) on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=53 Participants saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation Any AE	38 participants	42 participants
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation Severe or life-threatening AE	3 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation WFT or study due to AEs	1 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation Treatment-related AE	12 participants	8 participants
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation Deaths	0 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation Serious AEs other than death	2 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation Treatment-related serious AEs	0 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation WFT or study due to treatment-related AEs	0 participants	1 participants

Adverse Events

Reslizumab 3 mg/kg

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Reslizumab 3 mg/kg n=53 participants at risk reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=53 participants at risk saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
Infections and infestations PNEUMONIA	1.9% 1/53 • Number of events 1 • From start of study drug through 15 weeks + 30 days	0.00% 0/53 • From start of study drug through 15 weeks + 30 days
Respiratory, thoracic and mediastinal disorders ASTHMA	1.9% 1/53 • Number of events 1 • From start of study drug through 15 weeks + 30 days	0.00% 0/53 • From start of study drug through 15 weeks + 30 days
Vascular disorders HYPERTENSION	0.00% 0/53 • From start of study drug through 15 weeks + 30 days	1.9% 1/53 • Number of events 1 • From start of study drug through 15 weeks + 30 days

Other adverse events

Measure	Reslizumab 3 mg/kg n=53 participants at risk reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles	Placebo n=53 participants at risk saline placebo IV on Day 0 of each 28-day (+/- 7 days) cycle, for 4 cycles
General disorders FATIGUE	7.5% 4/53 • Number of events 4 • From start of study drug through 15 weeks + 30 days	3.8% 2/53 • Number of events 2 • From start of study drug through 15 weeks + 30 days
Infections and infestations BRONCHITIS	3.8% 2/53 • Number of events 2 • From start of study drug through 15 weeks + 30 days	5.7% 3/53 • Number of events 3 • From start of study drug through 15 weeks + 30 days
Infections and infestations NASOPHARYNGITIS	20.8% 11/53 • Number of events 14 • From start of study drug through 15 weeks + 30 days	9.4% 5/53 • Number of events 6 • From start of study drug through 15 weeks + 30 days
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	3.8% 2/53 • Number of events 3 • From start of study drug through 15 weeks + 30 days	9.4% 5/53 • Number of events 5 • From start of study drug through 15 weeks + 30 days
Nervous system disorders HEADACHE	3.8% 2/53 • Number of events 3 • From start of study drug through 15 weeks + 30 days	9.4% 5/53 • Number of events 5 • From start of study drug through 15 weeks + 30 days
Respiratory, thoracic and mediastinal disorders PHARYNGOLARYNGEAL PAIN	5.7% 3/53 • Number of events 3 • From start of study drug through 15 weeks + 30 days	0.00% 0/53 • From start of study drug through 15 weeks + 30 days

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 215-591-3000

Email: ustevatrials@tevapharm.com

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