Trial Outcomes & Findings for An Efficacy and Safety Study of Reslizumab Subcutaneous in Patients With Oral Corticosteroid Dependent Asthma and Elevated Blood Eosinophils (NCT NCT02501629)

Last Updated: 2021-11-09

Results Overview

The primary endpoint was the 5-level categorized percent reduction in OCS dose during weeks 20 to 24 compared with the optimized dose at baseline. The primary analysis incorporated data from all randomized patients. Analysis of the primary and secondary variables related to categorical OCS dose reduction incorporated missing data as non-responders. No decrease indicates there was no decrease in OCS, loss of baseline asthma control during weeks 20 to 24, or discontinuation from study drug.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

177 participants

Primary outcome timeframe

Baseline (Day 1), Weeks 20-24

Results posted on

2021-11-09

Participant Flow

A total of 273 patients with OCS-dependent severe eosinophilic asthma were screened, and 180 of these patients (at 78 centers) were considered eligible for enrollment. Three of the eligible patients were not randomized due to failure to meet randomization criteria.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Overall Study STARTED	89	88
Overall Study COMPLETED	84	81
Overall Study NOT COMPLETED	5	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Overall Study Death	0	1
Overall Study Withdrawn from study by sponsor	1	0
Overall Study Early termination by sponsor	1	0
Overall Study Withdrawal by Subject	3	5
Overall Study Subject did not return to site	0	1

Baseline Characteristics

An Efficacy and Safety Study of Reslizumab Subcutaneous in Patients With Oral Corticosteroid Dependent Asthma and Elevated Blood Eosinophils

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.	Total n=177 Participants Total of all reporting groups
Age, Continuous	53.1 years STANDARD_DEVIATION 11.99 • n=5 Participants	55.5 years STANDARD_DEVIATION 12.72 • n=7 Participants	54.3 years STANDARD_DEVIATION 12.38 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	60 Participants n=7 Participants	117 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=5 Participants	22 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=5 Participants	65 Participants n=7 Participants	137 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	80 Participants n=5 Participants	72 Participants n=7 Participants	152 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Age Group 12 to <18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age Group 18 to <65 years	74 Participants n=5 Participants	63 Participants n=7 Participants	137 Participants n=5 Participants
Age Group >=65 years	14 Participants n=5 Participants	25 Participants n=7 Participants	39 Participants n=5 Participants
Weight	82.69 kg STANDARD_DEVIATION 18.949 • n=5 Participants	79.58 kg STANDARD_DEVIATION 21.390 • n=7 Participants	81.14 kg STANDARD_DEVIATION 20.202 • n=5 Participants
Body Mass Index	29.859 kg/m^2 STANDARD_DEVIATION 6.3499 • n=5 Participants	29.389 kg/m^2 STANDARD_DEVIATION 8.0105 • n=7 Participants	29.625 kg/m^2 STANDARD_DEVIATION 7.2067 • n=5 Participants
Region Group US/Canada	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Region Group Europe	58 Participants n=5 Participants	47 Participants n=7 Participants	105 Participants n=5 Participants
Region Group Other	21 Participants n=5 Participants	32 Participants n=7 Participants	53 Participants n=5 Participants
Oral Corticosteroid (OCS) Dose at Baseline	10.37 mg STANDARD_DEVIATION 6.435 • n=5 Participants	10.37 mg STANDARD_DEVIATION 6.807 • n=7 Participants	10.37 mg STANDARD_DEVIATION 6.604 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Weeks 20-24

Population: Intent to Treat (ITT) Analysis set; missing data are included as non-responders (no decrease).

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline 90% to 100%	20 Participants	18 Participants
Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline 75% to <90%	4 Participants	8 Participants
Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline 50% to <75%	8 Participants	13 Participants
Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline >0% to <50%	9 Participants	7 Participants
Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline No decrease	48 Participants	42 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 20-24

Population: ITT Analysis set; missing data are included as non-responders (No).

Percentage of patients whose OCS dose at weeks 20-24 was reduced \>=50% compared to baseline while maintaining asthma control. Patients listed as "no" did not achieve the 50% reduction in baseline OCS dose goal, or did achieve that goal but lost asthma control during weeks 20 to 24, or discontinued from study drug.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control Yes	36 percentage of participants	44 percentage of participants
Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control No	64 percentage of participants	56 percentage of participants

SECONDARY outcome

Timeframe: Weeks 20-24

Population: ITT Analysis set; missing data are included as non-responders (No).

Percentage of participants whose OCS dose at weeks 20-24 was \<=5 mg and they maintained asthma control. Patients listed as "no" had a week 20-24 OCS dose \> 5 mg, or whose OCS dose was \<=5 mg at weeks 20-24 but did not maintain asthma control, or they discontinued from study drug.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control Yes	38 percentage of participants	42 percentage of participants
Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control No	62 percentage of participants	58 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 20-24

Population: ITT analysis population with available data using the on-treatment approach.

The baseline OCS dose is the prescribed optimized OCS dose following the OCS optimization period. Endpoint data are presented using an on-treatment approach. In this context, 'endpoint' was defined as the last observation obtained at a scheduled or qualified early termination visit during the treatment period. Weeks 20-24 data is included between the Week 20 dose and Week 24 for completed patients; last dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early. Measurements collected outside of these defined timeframes are excluded from the analyses. The mixed model repeated measures (MMRM) included fixed effects for treatment, visit, treatment by visit interaction, age group, and OCS dose group, duration of OCS use and baseline value as covariates, and patient as a random effect. Unstructured covariance was assumed for the repeated measures.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=84 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 Using a Mixed Model for Repeated Measures	-40.34 percent change Standard Error 17.318	-58.08 percent change Standard Error 17.633

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 20-24

Population: ITT Analysis set; missing data are included as non-responders (No).

Percentage of participants whose OCS dose at weeks 20-24 was reduced by at least 5mg from baseline and maintained asthma control. Patients listed as "no" had a week 20-24 OCS dose that did not meet the threshold of a 5mg reduction, or whose OCS dose met the threshold but did not maintain asthma control, or discontinued from study drug.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control Yes	35 percentage of participants	41 percentage of participants
Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control No	65 percentage of participants	59 percentage of participants

SECONDARY outcome

Timeframe: Day 1 through Week 24

Population: ITT Analysis Set

The annual exacerbation rate is based on clinical asthma exacerbations reported by the investigator in the eCRF.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Annualized Rate of Clinical Asthma Exacerbations (CAEs)	1.86 CAEs / year Interval 1.283 to 2.682	1.51 CAEs / year Interval 1.052 to 2.177

SECONDARY outcome

Timeframe: Weeks 20-24

Population: ITT Analysis set; missing data are included as non-responders (No).

Percentage of participants who discontinue use of OCS during weeks 20-24 while maintaining asthma control. Patients listed as "no" continued to use OCS during weeks 20-24, or who discontinued use of OCS during weeks 20-24 but lost control of their asthma, or discontinued from study drug.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control Yes	22 percentage of participants	20 percentage of participants
Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control No	78 percentage of participants	80 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 24 or early withdrawal.

Treatment-emergent responses were defined as a positive sample post-baseline (negative baseline) OR a titer increase of \>=4-fold relative to a positive baseline sample. Two types of antibody assay were performed, an immunogenicity status assay (ADA) and neutralizing assay (NAb). The ADA assay produces a positive or negative result. For samples with a positive result, a neutralizing assay was performed, which also produces a positive or negative result.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses Positive ADA samples	0 Participants	11 Participants
Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses Positive Nab samples	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to Week 24 (end of treatment visit); Data were included between Day 1 and Week 24 for completed patients, and Day 1 and 4 weeks after the last dose of study drug for patients who discontinued treatment early.

Population: Safety analysis set

An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product, regardless of whether it has a causal relationship with this treatment. In this study, asthma exacerbations (which are efficacy parameters) should not be recorded as adverse events unless assessed by the investigator as more severe than the patient's usual disease course. Relation of AE to treatment was determined by the investigator. Serious AEs include 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 patient and required medical intervention to prevent the previously listed serious outcomes. Treatment-related adverse events or adverse events related to OCS use included events with missing relationship to study drug or OCS use, respectively.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 Participants Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Participants With Adverse Events Treatment-related SAE	0 Participants	0 Participants
Participants With Adverse Events AE related to OCS use	2 Participants	5 Participants
Participants With Adverse Events Any AE	47 Participants	57 Participants
Participants With Adverse Events Treatment-related AE	3 Participants	7 Participants
Participants With Adverse Events Serious AE (SAE)	4 Participants	10 Participants
Participants With Adverse Events SAE resulting in death	0 Participants	1 Participants
Participants With Adverse Events AE leading to treatment discontinuation	1 Participants	0 Participants
Participants With Adverse Events AE related to OCS withdrawal	2 Participants	3 Participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Reslizumab 110 mg

Serious events: 10 serious events

Other events: 20 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=89 participants at risk Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 participants at risk Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Gastrointestinal disorders Inguinal hernia	0.00% 0/89 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24
General disorders Sudden death	0.00% 0/89 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24
Immune system disorders Drug hypersensitivity	0.00% 0/89 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24
Infections and infestations Cellulitis	0.00% 0/89 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24
Infections and infestations Influenza	0.00% 0/89 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24
Infections and infestations Pneumonia	0.00% 0/89 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24
Infections and infestations Pneumonia bacterial	1.1% 1/89 • Number of events 1 • Day 1 to Week 24	0.00% 0/88 • Day 1 to Week 24
Injury, poisoning and procedural complications Contusion	1.1% 1/89 • Number of events 1 • Day 1 to Week 24	0.00% 0/88 • Day 1 to Week 24
Injury, poisoning and procedural complications Facial bones fracture	1.1% 1/89 • Number of events 1 • Day 1 to Week 24	0.00% 0/88 • Day 1 to Week 24
Injury, poisoning and procedural complications Fibula fracture	1.1% 1/89 • Number of events 1 • Day 1 to Week 24	0.00% 0/88 • Day 1 to Week 24
Injury, poisoning and procedural complications Foot fracture	1.1% 1/89 • Number of events 1 • Day 1 to Week 24	0.00% 0/88 • Day 1 to Week 24
Injury, poisoning and procedural complications Head injury	1.1% 1/89 • Number of events 1 • Day 1 to Week 24	0.00% 0/88 • Day 1 to Week 24
Injury, poisoning and procedural complications Rib fracture	1.1% 1/89 • Number of events 1 • Day 1 to Week 24	0.00% 0/88 • Day 1 to Week 24
Nervous system disorders Syncope	0.00% 0/89 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Asthma	2.2% 2/89 • Number of events 2 • Day 1 to Week 24	3.4% 3/88 • Number of events 3 • Day 1 to Week 24

Other adverse events

Other adverse events
Measure	Placebo n=89 participants at risk Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Reslizumab 110 mg n=88 participants at risk Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses.
Infections and infestations Bronchitis	4.5% 4/89 • Number of events 4 • Day 1 to Week 24	6.8% 6/88 • Number of events 6 • Day 1 to Week 24
Infections and infestations Upper respiratory tract infection	5.6% 5/89 • Number of events 5 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24
Infections and infestations Viral upper respiratory tract infection	5.6% 5/89 • Number of events 5 • Day 1 to Week 24	12.5% 11/88 • Number of events 13 • Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Asthma	4.5% 4/89 • Number of events 6 • Day 1 to Week 24	5.7% 5/88 • Number of events 6 • Day 1 to Week 24
Vascular disorders Hypertension	5.6% 5/89 • Number of events 5 • Day 1 to Week 24	1.1% 1/88 • Number of events 1 • Day 1 to Week 24

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 1-888-483-8279

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.
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