A Study to Evaluate the Pharmacokinetics of MEDI9929 (AMG 157) in Adolescents With Mild to Moderate Asthma

Study Overview
=================
Brief Summary
-----------------
To evaluate the PK profile of a single-dose of 140 mg subcutaneous (SC) administration of MEDI9929 (AMG 157) in adolescent subjects with mild to moderate asthma.

Detailed Description
-----------------
The primary objective is to evaluate the PK profile of a single-dose of 140 mg subcutaneous (SC) administration of MEDI9929 (AMG 157) in adolescent subjects with mild to moderate asthma. The secondary objective is to evaluate the safety and tolerability of MEDI9929 and to evaluate the immunogenicity of MEDI9929 (AMG 157). The exploratory objective is to evaluate the effect of MEDI9929 (AMG 157) on pulmonary function

Official Title
-----------------
A Phase 1, Open-label Study to Evaluate the Pharmacokinetics of MEDI9929 (AMG 157) in Adolescents With Mild to Moderate Asthma

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: MEDI9929, 140 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Age 12 to 17 years (inclusive) at both screening and Day 1. Physician diagnosed asthma for a minimum of 6 months prior to screening. Physician prescribed daily use of asthma controller medication Prebronchodilator FEV1 of ≥ 70% of predicted normal value at screening. A postbronchodilator increase in FEV1 ≥ 12% and ≥ 200 mL at screening. If on allergen immunotherapy, subjects must be on a stable maintenance dose and schedule ≥ 1 month prior to Visit 1. Weight ≥ 30 kg at both screening and Day 1. Body mass index for age at both screening and Day 1 that is between 5th and 95th percentile Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception from screening Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from screening Exclusion Criteria: History of a deterioration in asthma that required a burst of systemic corticosteroids within 3 months of screening, up to and including Day 1. Clinical characteristics at either screening or Day 1 that are consistent with uncontrolled asthma as described in GINA guideline. History of hospitalization (overnight admission) for asthma during the 6 months prior to screening. History of intubation for the management of a deterioration in asthma. History of systemic corticosteroid use for the maintenance treatment of asthma within 3 months prior to screening. History of allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy. Any active medical condition other than asthma, that in the opinion of the investigator and/or medical monitor, may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study (subjects with atopic skin conditions and allergic rhinitis are permitted). Pregnant or breastfeeding females. Current tobacco smoking or cessation of smoking for ≤ 6months prior to screening. Any clinically relevant abnormal findings which in the opinion of the investigator or medical monitor, may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study. Evidence of active liver disease, Positive hepatitis B or hepatitis C virus A positive human immunodeficiency virus (HIV) test at screening or subject taking antiretroviral medications Major surgery within 8 weeks prior to Visit 1, or planned in-patient surgery or hospitalization during the study period. History of any known primary immunodeficiency disorder History of a clinically significant infection A helminth parasitic infection within 24 weeks of Visit 1 that has not been treated or has not responded to standard of care therapy. History of cancer.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI9929, 140 mg, Cohort 1 (12 to 14 years)<br>On Day 1, one MEDI9929 subcutaneous injection of 70 mg was given into the anterior aspect of one thigh immediately followed by the second injection of 70 mg into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants with 12 to 14 years of age. | Drug: MEDI9929, 140 mg<br>* On Day 1, two MEDI9929 subcutaneous injection of 70 mg each were given into the anterior aspect of one thigh immediately followed by the second injection into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants of 12 to 17 years of age.<br>* Other names: Subcutaneous single-dose;|
| Experimental: MEDI9929, 140 mg, Cohort 2 (15 to 17 years)<br>On Day 1, one MEDI9929 subcutaneous injection of 70 mg was given into the anterior aspect of one thigh immediately followed by the second injection of 70 mg into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants with 15 to 17 years of age. | Drug: MEDI9929, 140 mg<br>* On Day 1, two MEDI9929 subcutaneous injection of 70 mg each were given into the anterior aspect of one thigh immediately followed by the second injection into the anterior aspect of the contralateral thigh to make the required dose of 140 mg in participants of 12 to 17 years of age.<br>* Other names: Subcutaneous single-dose;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity]) | The pharmacokinetic (PK) parameter AUC (0 to infinity) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 
| Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) | The PK parameter AUC (0-t) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 
| Dose-normalized AUC (0-infinity) (AUC [0 Infinity]/D) | The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 
| Maximum Observed Serum Concentration (Cmax) | The PK parameter Cmax was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 
| Dose-normalized Cmax (Cmax/D) | The Cmax/D is the maximum observed concentration post dose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 
| Time to Reach Cmax (Tmax) | The Tmax is the time to maximum observed serum concentration of MEDI9929. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 
| Terminal Phase Elimination Half Life (t1/2,z) | The t½,z is the time measured for the serum drug concentration of MEDI9929 to decrease by one half. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 
| Apparent Clearance (CL/F) | The PK parameter CL/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 
| Apparent Steady-state Volume of Distribution (Vss/F) | The PK parameter Vss/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay. | Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events | An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) is any AE resulting in any of the following outcomes such as death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. A TEAE is defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0 | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 | 
| Treatment-emergent Adverse Events Related to Vital Sign Parameters and Physical Findings | Vital signs (blood pressure, temperature, pulse, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported. | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 | 
| Treatment-emergent Adverse Events Related to Laboratory Parameters | Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell count with differential, red blood cell count, hematocrit, hemoglobin and platelet count); serum chemistry: calcium, chloride, potassium, sodium, bicarbonate, aspartate transaminase, alanine transaminase, albumin, uric acid, creatinine, total bilirubin, glucose, alkaline phosphatase, blood urea nitrogen, total protein, and gamma glutamyl transferase; and urinalysis (nitrites, protein, glucose, ketones, urine drug screen, blood, and bilirubin). Number of participants with TEAEs related to laboratory evaluations were reported. | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 | 
| Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Computerized triplicate 12-lead ECGs as well as Qualitative 12-lead ECGs were obtained during the study. ECG parameters included heart rate, PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with TEAEs related to ECG after the start of study drug were to be reported. | From the start of study drug administration up to end of follow-up period, assessed up to Day 85 | 
| Number of Participants Positive for Anti-drug Antibodies and With Neutralizing Antibodies for MEDI9929 at Any Visit | Blood samples for immunogenicity assessment included the determination of anti-drug antibodies (ADA) for MEDI9929. The incidence rate of positive serum antibodies to MEDI9929 were presented. | Days 1 (predose), 29, 57 and 85 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Asthma