Clinical Trial Results:
A Single-Dose, Open-Label, Parallel Group Study to Characterize the Pharmacokinetics, Pharmacodynamics, Immunogenicity, Safety, and Tolerability of Reslizumab Following Subcutaneous Administration in Children with Asthma (6 to Less Than 12 Years of Age)
Summary
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EudraCT number |
2017-002060-40 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
15 Feb 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Jul 2018
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First version publication date |
19 Jul 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C38072-AS-10069
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Teva Branded Pharmaceutical Products R&D, Inc
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Sponsor organisation address |
41 Moores Road, Frazer, Pennsylvania, United States, 19355
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Public contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 215-591-3000, info.era-clinical@teva.de
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Scientific contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 215-591-3000, info.era-clinical@teva.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001202-PIP02-13 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Aug 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Feb 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of reslizumab in pediatric patients with asthma 6 to less than 12 years of age following administration of a single subcutaneous (sc) dose.
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Protection of trial subjects |
This study was conducted in full accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (eg, Code of Federal Regulations [CFR] Title 21, Parts 50, 54, 56, 312, and 314).
The investigator, or a qualified person designated by the investigator, fully informed the patient and parent or other legally acceptable representative of all pertinent aspects of the study, including the written information approved by the IRB. All written and/or oral information about the study was provided in a language as nontechnical as practical and understood by the parent or legally acceptable representative, and the patient as far as is practical. The patient and parent/legal representative were given ample time and opportunity to inquire about details of the study and to decide whether or not to participate in the study. The above was detailed in the source documentation.
A personally signed and dated informed consent form was obtained from each parent/legal representative and a signed and dated assent form was obtained from each patient (if the patient was able) before any study-specific procedures or assessments were done and after the aims,
methods, anticipated benefits, and potential hazards were explained; according to local IRB requirements. The forms were also signed and dated by the person who conducted the informed consent discussion. The investigator will keep the original consent and assent forms, and copies were given to the parent(s)/guardian(s) of the patients. It was also explained to the patients (and parent/legal representative) that they were free to refuse entry into the study and free to withdraw from the study at any time without prejudice to future treatment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Aug 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 37
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Worldwide total number of subjects |
37
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
37
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 56 patients with asthma were screened for enrollment into this study. Of the 56 patients screened, 37 patients at 6 centers in the US were randomized into the study. | ||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Of the 19 patients who were not randomized, 14 patients were excluded on the basis of inclusion/exclusion/randomization criteria, and 5 patients withdrew consent. Randomized patients were assigned 1:1:1 to one of the three treatment regimens (reslizumab 33, 110, and 165 mg sc). | ||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
Blinding implementation details |
Note that the study was randomised but not controlled.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Reslizumab 33 mg | ||||||||||||||||||||||||||||
Arm description |
A single 33-mg subcutaneous (sc) injection of reslizumab in the upper arm on Day 1. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
reslizumab
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Investigational medicinal product code |
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Other name |
CEP-38072, Cinqair, Cinqaero
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Drug was supplied in pre-filled syringes containing either 33, 55, or 110 mg. Injections were made in the upper arm the morning of Day 1. Patients in the 165 mg treatment arm were given two sequential injections (55 mg and 110 mg) in the same upper arm at least 1 inch away from each other.
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Arm title
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Reslizumab 110 mg | ||||||||||||||||||||||||||||
Arm description |
A single 110-mg subcutaneous (sc) injection of reslizumab in the upper arm on Day 1. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
reslizumab
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Investigational medicinal product code |
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Other name |
CEP-38072, Cinqair, Cinqaero
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Drug was supplied in pre-filled syringes containing either 33, 55, or 110 mg. Injections were made in the upper arm the morning of Day 1. Patients in the 165 mg treatment arm were given two sequential injections (55 mg and 110 mg) in the same upper arm at least 1 inch away from each other.
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Arm title
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Reslizumab 165 mg | ||||||||||||||||||||||||||||
Arm description |
Patients in the 165 mg treatment arm were given two sequential injections (55 mg and 110 mg) in the same upper arm at least 1 inch away from each other on the morning of Day 1. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
reslizumab
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Investigational medicinal product code |
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Other name |
CEP-38072, Cinqair, Cinqaero
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Drug was supplied in pre-filled syringes containing either 33, 55, or 110 mg. Injections were made in the upper arm the morning of Day 1. Patients in the 165 mg treatment arm were given two sequential injections (55 mg and 110 mg) in the same upper arm at least 1 inch away from each other.
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Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: One patient (reslizumab 165 mg) was excluded from the pharmacokinetic analysis set because pharmacokinetic samples were not collected at critical time points (48, 648, 1320, and 1992 hours [days 3, 28, 56, and 84]); therefore, 35 of the 36 dosed patients were included in the pharmacokinetic analysis set. |
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Baseline characteristics reporting groups
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Reporting group title |
Reslizumab 33 mg
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Reporting group description |
A single 33-mg subcutaneous (sc) injection of reslizumab in the upper arm on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Reslizumab 110 mg
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Reporting group description |
A single 110-mg subcutaneous (sc) injection of reslizumab in the upper arm on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Reslizumab 165 mg
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Reporting group description |
Patients in the 165 mg treatment arm were given two sequential injections (55 mg and 110 mg) in the same upper arm at least 1 inch away from each other on the morning of Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Reslizumab 33 mg
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Reporting group description |
A single 33-mg subcutaneous (sc) injection of reslizumab in the upper arm on Day 1. | ||
Reporting group title |
Reslizumab 110 mg
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Reporting group description |
A single 110-mg subcutaneous (sc) injection of reslizumab in the upper arm on Day 1. | ||
Reporting group title |
Reslizumab 165 mg
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Reporting group description |
Patients in the 165 mg treatment arm were given two sequential injections (55 mg and 110 mg) in the same upper arm at least 1 inch away from each other on the morning of Day 1. |
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End point title |
Maximum Observed Serum Drug Concentration (Cmax) | ||||||||||||||||
End point description |
Maximum observed serum drug concentration, obtained directly from the observed concentration-time data.
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End point type |
Primary
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End point timeframe |
PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84
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Notes [1] - PK analysis set [2] - PK analysis set [3] - PK analysis set |
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Statistical analysis title |
Dose Proportionality of Reslizumab: Cmax | ||||||||||||||||
Statistical analysis description |
A power model was fit separately to describe the linear relationship between Cmax and dose (33 mg, 110 mg, and 165 mg) using the least-squares linear
regression model as follows: ln(Cmax) = α + β ln(dose) + ε
This linear model was used to provide a 90% confidence interval (CI) for β (slope). Dose proportionality was concluded if the 90% CI of the slope β lies entirely within the limits (0.861 to 1.139).
However, the study was not powered to statistically demonstrate dose proportionality
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Comparison groups |
Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [4] | ||||||||||||||||
Method |
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Parameter type |
Slope | ||||||||||||||||
Point estimate |
0.882
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Confidence interval |
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level |
90% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.729 | ||||||||||||||||
upper limit |
1.035 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.09
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Notes [4] - dose proportionality. This analysis is without weight as a covariate. |
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Statistical analysis title |
Dose Proportionality (Covariate Weight): Cmax | ||||||||||||||||
Statistical analysis description |
The power model, ln (parameter) = a + b*ln (dose) + c*Weight + error, was used to estimate the slope and corresponding 90% confidence interval. Dose proportionality was to have been concluded if the 90% confidence interval of the slope lay entirely within 0.861 to 1.139 over the dose range of 33 mg to 165 mg. However, the study was not powered to statistically demonstrate dose proportionality.
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Comparison groups |
Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [5] | ||||||||||||||||
Method |
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Parameter type |
Slope | ||||||||||||||||
Point estimate |
0.931
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Confidence interval |
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level |
90% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.827 | ||||||||||||||||
upper limit |
1.035 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.061
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Notes [5] - Dose proportionality. This analysis is with weight as a covariate. |
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Statistical analysis title |
Dose Proportionality (Co- Weight, Sex, Age): Cmax | ||||||||||||||||
Statistical analysis description |
The power model, ln (parameter) = a + b*ln (dose) + c*Weight + d*Sex + e*Age + error, was used to estimate the slope and corresponding 90% confidence interval. Dose proportionality was to have been concluded if the 90% confidence interval of the slope lay entirely within 0.861 to 1.139 over the dose range of 33 mg to 165 mg. However, the study was not powered to statistically demonstrate dose proportionality.
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Comparison groups |
Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [6] | ||||||||||||||||
Method |
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Parameter type |
Slope | ||||||||||||||||
Point estimate |
0.93
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Confidence interval |
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level |
90% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.825 | ||||||||||||||||
upper limit |
1.034 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.062
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Notes [6] - Dose proportionality |
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End point title |
Area Under the Serum Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Drug Concentration (AUC 0-t) | ||||||||||||||||
End point description |
Area under the serum concentration-time curve (AUC) from time 0 to the time of the last quantifiable drug concentration; calculated by the linear trapezoidal
method.
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End point type |
Primary
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End point timeframe |
PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84
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Notes [7] - PK analysis set [8] - PK analysis set [9] - PK analysis set |
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Statistical analysis title |
Dose Proportionality of Reslizumab: AUC0-t | ||||||||||||||||
Statistical analysis description |
A power model was fit separately to describe the linear relationship between AUC0-t and dose using the least-squares linear
regression model as follows: ln(AUC0-t) = α + β ln(dose) + ε
This linear model was used to provide a 90% confidence interval (CI) for β (slope). Dose proportionality was concluded if the 90% CI of the slope β lies entirely within the limits (0.861 to 1.139). However, the study was not powered to statistically demonstrate dose proportionality.
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Comparison groups |
Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [10] | ||||||||||||||||
Method |
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Parameter type |
Slope | ||||||||||||||||
Point estimate |
0.982
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Confidence interval |
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level |
90% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.833 | ||||||||||||||||
upper limit |
1.131 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.088
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Notes [10] - dose proportionality |
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Statistical analysis title |
Dose Proportionality (Covariate Weight): AUC0-t | ||||||||||||||||
Statistical analysis description |
The power model, ln (parameter) = a + b*ln (dose) + c*Weight + error, was used to estimate the slope and corresponding 90% confidence interval. Dose proportionality was to have been concluded if the 90% confidence interval of the slope lay entirely within 0.861 to 1.139 over the dose range of 33 mg to 165 mg. However, the study was not powered to statistically demonstrate dose proportionality.
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Comparison groups |
Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [11] | ||||||||||||||||
Method |
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Parameter type |
Slope | ||||||||||||||||
Point estimate |
1.016
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Confidence interval |
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level |
90% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.886 | ||||||||||||||||
upper limit |
1.145 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.077
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Notes [11] - dose proportionality |
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Statistical analysis title |
Dose Proportionality(Co- Weight, Sex, Age): AUC0-t | ||||||||||||||||
Statistical analysis description |
The power model, ln (parameter) = a + b*ln (dose) + c*Weight + d*Sex + e*Age + error, was used to estimate the slope and corresponding 90% confidence interval. Dose proportionality was to have been concluded if the 90% confidence interval of the slope lay entirely within 0.861 to 1.139 over the dose range of 33 mg to 165 mg. However, the study was not powered to statistically demonstrate dose proportionality.
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Comparison groups |
Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [12] | ||||||||||||||||
Method |
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Parameter type |
Slope | ||||||||||||||||
Point estimate |
1.025
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Confidence interval |
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level |
90% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.9 | ||||||||||||||||
upper limit |
1.151 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.074
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Notes [12] - dose proportionality |
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End point title |
Area Under the Serum Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUC0-∞) | ||||||||||||||||
End point description |
AUC from time 0 extrapolated to infinity; calculated as [AUCt + (Ct/λz)] where Ct is the last quantifiable serum drug concentration.
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End point type |
Primary
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End point timeframe |
PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84
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Notes [13] - PK analysis set [14] - PK analysis set [15] - PK analysis set |
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Statistical analysis title |
Dose Proportionality of Reslizumab: AUC0-∞ | ||||||||||||||||
Statistical analysis description |
A power model was fit separately to describe the linear relationship between AUC0-∞ and dose (33, 110, and 165 mg) using the least-squares linear
regression model as follows: ln(AUC0-∞) = α + β ln(dose) + ε
This linear model was used to provide a 90% confidence interval (CI) for β (slope). Dose proportionality was concluded if the 90% CI of the slope β lies entirely within the limits (0.861 to 1.139). However, the study was not powered to statistically demonstrate dose proportionality.
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Comparison groups |
Reslizumab 110 mg v Reslizumab 165 mg v Reslizumab 33 mg
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [16] | ||||||||||||||||
Method |
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Parameter type |
Slope | ||||||||||||||||
Point estimate |
0.975
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Confidence interval |
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level |
90% | ||||||||||||||||
sides |
2-sided
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||||||||||||||||
lower limit |
0.822 | ||||||||||||||||
upper limit |
1.127 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.09
|
||||||||||||||||
Notes [16] - dose proportionality |
|||||||||||||||||
Statistical analysis title |
Dose Proportionality (Covariate Weight): AUC0-∞ | ||||||||||||||||
Statistical analysis description |
The power model, ln (parameter) = a + b*ln (dose) + c*Weight + error, was used to estimate the slope and corresponding 90% confidence interval. Dose proportionality was to have been concluded if the 90% confidence interval of the slope lay entirely within 0.861 to 1.139 over the dose range of 33 mg to 165 mg. However, the study was not powered to statistically demonstrate dose proportionality.
|
||||||||||||||||
Comparison groups |
Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg
|
||||||||||||||||
Number of subjects included in analysis |
35
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [17] | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Slope | ||||||||||||||||
Point estimate |
1.006
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
90% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.868 | ||||||||||||||||
upper limit |
1.143 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.081
|
||||||||||||||||
Notes [17] - dose proportionality |
|||||||||||||||||
Statistical analysis title |
Dose Proportionality(Co- Weight, Sex, Age): AUC0-∞ | ||||||||||||||||
Statistical analysis description |
The power model, ln (parameter) = a + b*ln (dose) + c*Weight + d*Sex + e*Age + error, was used to estimate the slope and corresponding 90% confidence interval. Dose proportionality was to have been concluded if the 90% confidence interval of the slope lay entirely within 0.861 to 1.139 over the dose range of 33 mg to 165 mg. However, the study was not powered to statistically demonstrate dose proportionality.
|
||||||||||||||||
Comparison groups |
Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg
|
||||||||||||||||
Number of subjects included in analysis |
35
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [18] | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Slope | ||||||||||||||||
Point estimate |
1.016
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
90% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.881 | ||||||||||||||||
upper limit |
1.151 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.079
|
||||||||||||||||
Notes [18] - dose proportionality |
|
|||||||||||||||||
End point title |
Time to Maximum Observed Serum Drug Concentration (tmax) [19] | ||||||||||||||||
End point description |
Time to maximum observed serum drug concentration was obtained directly from the observed concentration-time data.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84
|
||||||||||||||||
Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||
|
|||||||||||||||||
Notes [20] - PK analysis set [21] - PK analysis set [22] - PK analysis set |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Apparent Terminal Elimination Half-life (t½) [23] | ||||||||||||||||
End point description |
Apparent terminal elimination half-life was calculated as [(ln 2)/λz].
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84
|
||||||||||||||||
Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||
|
|||||||||||||||||
Notes [24] - PK analysis set [25] - PK analysis set [26] - PK analysis set |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Apparent Total Body Clearance (CL/F) [27] | ||||||||||||||||
End point description |
Apparent total body clearance was calculated as dose/AUC0-∞.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84
|
||||||||||||||||
Notes [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||
|
|||||||||||||||||
Notes [28] - PK analysis set [29] - PK analysis set [30] - PK analysis set |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Apparent Volume of Distribution (Vz/F) [31] | ||||||||||||||||
End point description |
Apparent volume of distribution during the terminal phase was calculated as dose/(AUC0-∞ x λz).
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84
|
||||||||||||||||
Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||
|
|||||||||||||||||
Notes [32] - PK analysis set [33] - PK analysis set [34] - PK analysis set |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Apparent Serum Terminal Elimination Rate Constant (λz) [35] | ||||||||||||||||
End point description |
Apparent serum terminal elimination rate constant was estimated by linear regression of the terminal portion of the log-concentration by time curve in serum; a minimum of 3 non-BLQ data points in the elimination phase (not including Cmax) were used for the calculation. The λz would not be estimated if r-squared is less than 0.8.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84
|
||||||||||||||||
Notes [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||
|
|||||||||||||||||
Notes [36] - PK analysis set [37] - PK analysis set [38] - PK analysis set |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Blood Eosinophil Counts from Baseline to Day 28 [39] | ||||||||||||||||||||||||||||||||||||
End point description |
Blood samples for eosinophil measurement were collected prior to reslizumab administration (baseline) and 48, 144, 312 and 648 hours postdose. The blood eosinophil counts are the pharmacodynamic outcome.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
prior to study drug administration (day 1), and on days 3, 7, 14, 28
|
||||||||||||||||||||||||||||||||||||
Notes [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [40] - Pharmacodynamic analysis set [41] - Pharmacodynamic analysis set [42] - Pharmacodynamic analysis set |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Participants with a Positive Anti-Drug Antibody (ADA) Result by Visit | ||||||||||||||||||||||||||||||||
End point description |
Blood samples to test for the presence of ADAs were collected prior to reslizumab administration and at Day 14, 28, 56 and 84. The ADA analysis in human serum employed a validated homogeneous ELISA, and it was performed in a 3-tier approach consisting of screening, confirmatory, and titer assays.
Data represent the count of participants with a positive ADA status at each visit.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Day 1 predose, Days 14, 28, 56 and 84
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [43] - Safety analysis set [44] - Safety analysis set [45] - Safety analysis set |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Anti-Drug Antibody Titer Result by Visit | ||||||||||||||||||||||||||||||||||||
End point description |
Blood samples to test for the presence of ADAs were collected prior to reslizumab administration and at Day 14, 28, 56 and 84. The ADA analysis in human serum employed a validated homogeneous ELISA, and it was performed in a 3-tier approach consisting of screening, confirmatory, and titer assays.
Titer results are offered for patients with positive ADA tests at visits when blood samples for ADA tests were collected. The number of patients with positive ADA tests is reported in the previous outcome and repeated here in this outcome as the 'n' following the visit day. Values of 0 indicate that all patients had negative ADA analyses for that visit.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1 predose and Days 14, 28, 56 and 84
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [46] - Safety analysis set [47] - Safety analysis set [48] - Safety analysis set |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Participants with Adverse Events | ||||||||||||||||||||||||||||||||||||
End point description |
An adverse event 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. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an
AE which prevents normal daily activities. Relation of AE to treatment was determined by the
investigator and includes possibly, probably and definitely related categories. Serious AEs (SAE) 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1 to Day 84
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [49] - Safety analysis set [50] - Safety analysis set [51] - Safety analysis set |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Day 1 to Day 84
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Reslizumab 33 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
A single 33-mg subcutaneous (sc) injection of reslizumab in the upper arm on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Reslizumab 110 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
A single 110-mg subcutaneous (sc) injection of reslizumab in the upper arm on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Reslizumab 165 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients in the 165 mg treatment arm were given two sequential injections (55 mg and 110 mg) in the same upper arm at least 1 inch away from each other on the morning of Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |