C38072-AS-10069

Teva Branded Pharmaceutical Products R&D, Inc

41 Moores Road, Frazer, Pennsylvania, United States, 19355

Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 215-591-3000, info.era-clinical@teva.de

Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 215-591-3000, info.era-clinical@teva.de

Yes

No

Yes

Final

07 Aug 2017

No

Yes

15 Feb 2017

No

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.

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.

09 Aug 2016

No

No

United States: 37

37

0

0

0

0

0

37

0

0

0

0

Overall Trial (overall period)

Randomised - controlled

Note that the study was randomised but not controlled.

Yes

reslizumab

CEP-38072, Cinqair, Cinqaero

Solution for injection in pre-filled syringe

Subcutaneous use

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.

reslizumab

CEP-38072, Cinqair, Cinqaero

Solution for injection in pre-filled syringe

Subcutaneous use

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.

reslizumab

CEP-38072, Cinqair, Cinqaero

Solution for injection in pre-filled syringe

Subcutaneous use

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.

Reslizumab 33 mg

Reslizumab 110 mg

Reslizumab 165 mg

Reslizumab 33 mg

Reslizumab 110 mg

Reslizumab 165 mg

Maximum observed serum drug concentration, obtained directly from the observed concentration-time data.

Primary

PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84

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

Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg

35

Pre-specified

0.882

2-sided

Standard error of the mean

0.09

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.

Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg

35

Pre-specified

0.931

2-sided

Standard error of the mean

0.061

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.

Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg

35

Pre-specified

0.93

2-sided

Standard error of the mean

0.062

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.

Primary

PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84

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.

Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg

35

Pre-specified

0.982

2-sided

Standard error of the mean

0.088

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.

Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg

35

Pre-specified

1.016

2-sided

Standard error of the mean

0.077

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.

Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg

35

Pre-specified

1.025

2-sided

Standard error of the mean

0.074

AUC from time 0 extrapolated to infinity; calculated as [AUCt + (Ct/λz)] where Ct is the last quantifiable serum drug concentration.

Primary

PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84

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.

Reslizumab 110 mg v Reslizumab 165 mg v Reslizumab 33 mg

35

Pre-specified

0.975

2-sided

Standard error of the mean

0.09

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.

Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg

35

Pre-specified

1.006

2-sided

Standard error of the mean

0.081

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.

Reslizumab 33 mg v Reslizumab 110 mg v Reslizumab 165 mg

35

Pre-specified

1.016

2-sided

Standard error of the mean

0.079

Time to maximum observed serum drug concentration was obtained directly from the observed concentration-time data.

Primary

PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84

Apparent terminal elimination half-life was calculated as [(ln 2)/λz].

Primary

PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84

Apparent total body clearance was calculated as dose/AUC0-∞.

Primary

PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84

Apparent volume of distribution during the terminal phase was calculated as dose/(AUC0-∞ x λz).

Primary

PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84

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.

Primary

PK sampling times: prior to study drug administration (day 1), and on days 3, 7, 14, 28, 56 and 84

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.

Primary

prior to study drug administration (day 1), and on days 3, 7, 14, 28

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.

Secondary

Day 1 predose, Days 14, 28, 56 and 84

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.

Secondary

Day 1 predose and Days 14, 28, 56 and 84

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.

Secondary

Day 1 to Day 84

Day 1 to Day 84

19.0

Reslizumab 33 mg

Reslizumab 110 mg

Reslizumab 165 mg