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NCT03052725

A Study of Reslizumab in Patients 12 Years of Age and Older With Severe Eosinophilic Asthma

Terminated Phase 3 Results posted Last updated 14 December 2022
What this trial tests

Phase 3 trial testing reslizumab in Eosinophils, Asthma in 391 participants. Terminated before completion.

Timeline
10 March 2017
Primary endpoint
22 February 2018
22 February 2018

Quick facts

Lead sponsorTeva Branded Pharmaceutical Products R&D, Inc.
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment391
Start date10 March 2017
Primary completion22 February 2018
Estimated completion22 February 2018
Sites134 locations across France, Russia, Ukraine, Belgium, Germany, Hungary, Israel, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. — full company profile →

Who can join

12 and older, any sex, with Eosinophils, Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Participants With Treatment-Emergent Adverse Events (TEAEs) Primary · Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.

An adverse event is any untoward medical occurrence, regardless of whether it has a causal relationship with study treatment. In this study, asthma exacerbations should not be recorded as adverse events unless assessed by the investigator as more severe than the patient's usual disease course. The period for reporting treatment-emergent adverse events was defined as the period after the first dose of study drug was administered until the end of treatment visit. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient

>=1 TEAE
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo102
Reslizumab 110 mg; Previous Treatment Reslizumab114
>=1 treatment-related TEAE
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo7
Reslizumab 110 mg; Previous Treatment Reslizumab6
>=1 serious TEAE
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo5
Reslizumab 110 mg; Previous Treatment Reslizumab11
>=1 treatment-related, serious TEAE
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab0
>=1 TEAE leading to discontinuation
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2
Reslizumab 110 mg; Previous Treatment Reslizumab0
>=1 TEAE leading to death
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab0
Participants With Potentially Clinically Significant Abnormal Hematology Values Secondary · Week 0 (baseline), Weeks 8, 24, 36 plus any unscheduled visits

Participants are included in the counts if the worst study value reaches the following clinically significant levels: Eosinophils (high): \>=1.5\*10\^9/L and increase \>0 Hematocrit (low): \>=18 years old: \<0.32 L/L for females; \<0.37 L/L for males plus a decrease \>0 for both or 12 to \<18 years old: \<0.30 L/L and a decrease \>0 for both females and males Hemoglobin (low): \>=18 years old: \<=95 g/L and decrease \>0; 12 to \<18 years old: \<=100 g/L and decrease \>0 Leukocytes (high): \>=20\*10\^9/L and increase \>0 Leukocytes (low): \<=3\*10\^9/L and decrease \>0 Neutrophils (low): \<=1\

Participants with >=1 abnormality
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo8
Reslizumab 110 mg; Previous Treatment Reslizumab5
Eosinophils (high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo1
Reslizumab 110 mg; Previous Treatment Reslizumab0
Hematocrit (low)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo4
Reslizumab 110 mg; Previous Treatment Reslizumab2
Hemoglobin (low)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2
Reslizumab 110 mg; Previous Treatment Reslizumab0
Leukocytes (high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab1
Leukocytes (low)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2
Reslizumab 110 mg; Previous Treatment Reslizumab0
Neutrophils (low)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo1
Reslizumab 110 mg; Previous Treatment Reslizumab1
Platelets
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab1
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Secondary · Week 0 (baseline), Weeks 4, 8, 24, 36 plus any unscheduled visits

Participants are included in the counts if the worst study value reaches the following clinically significant levels: Alanine Aminotransferase (high): \>=3\* upper limit of normal (ULN) and increase \>0 Aspartate Aminotransferase (high): \>=3\* upper limit of normal (ULN) and increase \>0 Bilirubin (high): \>=34.2 micromol/L and increase \>0 Blood Urea Nitrogen (high): \>=10.71 mmol/L and increase \>0 Creatine Phosphokinase (high): \>10\* ULN and increase \>0 Creatine Phosphokinase (medium high): \>=3.1\*ULN and \<=10\*ULN and increase \>0 Creatinine (high): \>=177 micromol/L and increase \>0

Participants with >=1 abnormality
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo12
Reslizumab 110 mg; Previous Treatment Reslizumab10
Alanine Aminotransferase (high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo1
Reslizumab 110 mg; Previous Treatment Reslizumab2
Aspartate Aminotransferase (high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo1
Reslizumab 110 mg; Previous Treatment Reslizumab1
Bilirubin (high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2
Reslizumab 110 mg; Previous Treatment Reslizumab1
Blood Urea Nitrogen (high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2
Reslizumab 110 mg; Previous Treatment Reslizumab4
Creatine Phosphokinase (high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2
Reslizumab 110 mg; Previous Treatment Reslizumab1
Creatine Phosphokinase (medium high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo6
Reslizumab 110 mg; Previous Treatment Reslizumab4
Creatinine (high)
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab1
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Secondary · Weeks 4, 8, 12, 16, 20, 24, 28, and 36

The worst finding for participants in each tolerability and injection site domain from all treatment weeks is summarized. Local tolerability at the injection site was assessed approximately 1 hour after study drug administration. Severity was rated on a 4-level scale of none, mild, moderate and severe.

Pain - None
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo191
Reslizumab 110 mg; Previous Treatment Reslizumab194
Pain - Mild
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo3
Reslizumab 110 mg; Previous Treatment Reslizumab2
Pain - Moderate
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab0
Pain - Severe
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab0
Tenderness - None
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo193
Reslizumab 110 mg; Previous Treatment Reslizumab192
Tenderness - Mild
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo1
Reslizumab 110 mg; Previous Treatment Reslizumab4
Tenderness - Moderate
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab0
Tenderness - Severe
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab0
Participants With Potentially Clinically Significant Abnormal Vital Sign Values Secondary · Week 0 (baseline), Weeks 4, 8, 12, 16,20, 24, 28, 32, 36 plus any unscheduled visits

Participants are included in the counts if the worst study value reaches the following clinically significant levels: Diastolic blood pressure (high): \>100 mmHg and increase \>=12 for participants \>=18 years; \>85 mmHg and increase \>=12 for participants 12 - \< 18 years Pulse rate (high): \>100 beats/minute and increase \>=12 Respiratory rate (high): \>24 breaths/minute and increase \>=10 for participants \>=18 years \>20 breaths/minute and increase \>=10 for participants 12 - \< 18 years Systolic blood pressure (high): \>160 mmHg and increase \>=30 for participants \>=18 years; \>130 mmHg

Participants with >=1 abnormality
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo20
Reslizumab 110 mg; Previous Treatment Reslizumab16
Diastolic Blood Pressure - High
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0
Reslizumab 110 mg; Previous Treatment Reslizumab1
Pulse Rate - High
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo1
Reslizumab 110 mg; Previous Treatment Reslizumab2
Respiratory Rate - High
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2
Reslizumab 110 mg; Previous Treatment Reslizumab0
Systolic Blood Pressure - High
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2
Reslizumab 110 mg; Previous Treatment Reslizumab0
Temperature - High
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo1
Reslizumab 110 mg; Previous Treatment Reslizumab0
Temperature - Low
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo14
Reslizumab 110 mg; Previous Treatment Reslizumab13
Annualized Rate of Clinical Asthma Exacerbations (CAEs) Secondary · Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.

Data is included between the first dose of study drug to the end of treatment visit for completed participants, and the first dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early. Annual rate is defined as the number of events/(duration of treatment \[days\]/365.25). Participants with zero events are included.

GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.42± 1.104
Reslizumab 110 mg; Previous Treatment Reslizumab0.70± 1.538
Annualized Rate of Clinical Asthma Exacerbations (CAEs) Requiring Asthma-Specific Hospital Admissions or Emergency Room Visits Secondary · Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.

Data is included between the first dose of study drug to the end of treatment visit for completed participants, and the first dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early. Annual rate is defined as the number of events/(duration of treatment \[days\]/365.25). Participants with zero events are included.

GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.06± 0.362
Reslizumab 110 mg; Previous Treatment Reslizumab0.11± 0.514
Mean Number of Days of Hospital Stay During the Treatment Period Secondary · Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug

Participants with no hospitalizations are included.

GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.25± 1.658
Reslizumab 110 mg; Previous Treatment Reslizumab1.02± 7.848
Mean Number of School/Work Days Missed Due to Asthma During the Treatment Period Secondary · Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug

Participants with no school or work days missed due to asthma are included in the counts.

GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.11± 1.202
Reslizumab 110 mg; Previous Treatment Reslizumab0.00± 0.000
Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Secondary · Week 0 (baseline), Weeks 8, 24, 36

The FEV1 is the volume of air that can be forcibly exhaled from the lungs in the first second, measured in liters. Pre-bronchodilator spirometry assessments at designated clinic visits (weeks 0, 8, and 24, and 36) should only be performed after withholding short-acting bronchodilators (ie, inhaled short-acting beta-adrenergic agonists and/or short-acting anticholinergics) for at least 6 hours and long-acting bronchodilators ie, inhaled long-acting beta-adrenergic agonists and long acting anticholinergic agents) for at least 12 or 24 hours, according to their labeled dose schedule.

Baseline - observed value
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2.162± 0.980
Reslizumab 110 mg; Previous Treatment Reslizumab2.117± 0.927
Change at Week 8
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.099± 0.704
Reslizumab 110 mg; Previous Treatment Reslizumab0.031± 0.529
Change at Week 24
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.169± 0.851
Reslizumab 110 mg; Previous Treatment Reslizumab-0.020± 0.472
Change at Week 36
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.245± 0.677
Reslizumab 110 mg; Previous Treatment Reslizumab0.010± 0.550
Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Secondary · Week 0 (baseline), Weeks 1, 4, 8, 24, 36

A weekly average of daily morning ambulatory FEV1 (measured by the handheld spirometry device) was derived using 7-day window intervals. The average was calculated as the sum of all values divided by the number of non-missing assessments. There will be no imputation of missing data. At least 4 of the 7 measurements need to be recorded for a week to be included in the analysis; otherwise the week was treated as missing.

Baseline - observed value
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo2.057± 0.814
Reslizumab 110 mg; Previous Treatment Reslizumab2.027± 0.847
Change at Week 1
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.002± 0.345
Reslizumab 110 mg; Previous Treatment Reslizumab-0.044± 0.291
Change at Week 4
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.051± 0.490
Reslizumab 110 mg; Previous Treatment Reslizumab-0.049± 0.319
Change at Week 8
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.028± 0.463
Reslizumab 110 mg; Previous Treatment Reslizumab-0.039± 0.345
Change at Week 24
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.051± 0.492
Reslizumab 110 mg; Previous Treatment Reslizumab-0.062± 0.403
Change at Week 36
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo0.061± 0.273
Reslizumab 110 mg; Previous Treatment Reslizumab-0.053± 0.465
Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36 Secondary · Week 0 (baseline), Weeks 16-20, Weeks 32-36

Daily OCS dose is defined as total OCS dose in a day (accounting for reported dose and dose frequency) and converting the total daily dose to a prednisone-equivalent dose. Baseline dose is the prescribed OCS dose on the day of first dose of study drug in this study. Dose at Weeks 16-20 and 32-36 is the mean of all daily OCS doses during the week range. Percent change = 100 \* (absolute change / baseline dose)

% change at Week 16-20
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo-2.19± 51.347
Reslizumab 110 mg; Previous Treatment Reslizumab-6.96± 40.904
% change at Week 32-36
GroupValue95% CI
Reslizumab 110 mg; Previous Treatment Placebo-8.44± 24.236
Reslizumab 110 mg; Previous Treatment Reslizumab-8.75± 29.666

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Reslizumab 110 mg
Serious: 16/390 (4%)
Deaths: 0/390

Serious adverse events (18 terms)

ReactionSystemReslizumab 110 mg
PneumoniaInfections and infestations
AsthmaRespiratory, thoracic and mediastinal disorders
Abdominal distensionGastrointestinal disorders
DysphagiaGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
VomitingGastrointestinal disorders
Chest painGeneral disorders
AppendicitisInfections and infestations
InfluenzaInfections and infestations
Peritonsillar abscessInfections and infestations
Post procedural haematomaInjury, poisoning and procedural complications
Neck painMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Synovial cystMusculoskeletal and connective tissue disorders
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Abortion spontaneousPregnancy, puerperium and perinatal conditions
NephrolithiasisRenal and urinary disorders
Hypertensive crisisVascular disorders
Other adverse events (2 terms — click to expand)

ReactionSystemReslizumab 110 mg
Viral upper respiratory tract infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations

Most-reported serious reactions: Pneumonia, Asthma, Abdominal distension, Dysphagia, Inguinal hernia, Vomiting, Chest pain, Appendicitis.

Data from ClinicalTrials.gov NCT03052725 adverse events section.

Sponsor's own description

This is a multicenter, open-label (OL) extension study to obtain additional long-term safety data for subcutaneous (sc) administration of reslizumab treatment administered at a fixed dose of 110 mg in patients 12 years of age and older with severe eosinophilic asthma who completed the treatment period of a placebo-controlled Phase 3 trial of sc reslizumab. The study consists of a screening/baseline visit followed by a 36-week OL treatment period and a 15-week follow-up period.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons.
    Hussain M, Liu G. · · 2024 · cited 60× · PMID 38474348 · DOI 10.3390/cells13050384
  2. Packaging and Delivery of Asthma Therapeutics.
    Mathis BJ, Kusumoto M, Zaboronok A, Hiramatsu Y. · · 2021 · cited 9× · PMID 35056988 · DOI 10.3390/pharmaceutics14010092

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