Clinical trial NCT02512900: A Study to Evaluate the Pharmacokinetics of MEDI9929 (AMG 157) in Adolescents With Mild to Moderate Asthma
Official title: A Phase 1, Open-label Study to Evaluate the Pharmacokinetics of MEDI9929 (AMG 157) in Adolescents With Mild to Moderate Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Asthma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2015-07-31
Enrollment: 21
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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

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.

Primary outcomes:
measure: Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity])
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
measure: Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t])
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
measure: Dose-normalized AUC (0-infinity) (AUC [0 Infinity]/D)
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
measure: Dose-normalized Cmax (Cmax/D)
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
measure: Time to Reach Cmax (Tmax)
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
measure: Terminal Phase Elimination Half Life (t1/2,z)
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
measure: Apparent Clearance (CL/F)
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
measure: Apparent Steady-state Volume of Distribution (Vss/F)
timeFrame: Predose on Day 1 and Day 2, 4, 7, 11, 15, 22, 29, 43, 57 and 85 post-dose.
Secondary outcomes:
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events
timeFrame: From the start of study drug administration up to end of follow-up period, assessed up to Day 85
measure: Treatment-emergent Adverse Events Related to Vital Sign Parameters and Physical Findings
timeFrame: From the start of study drug administration up to end of follow-up period, assessed up to Day 85
measure: Treatment-emergent Adverse Events Related to Laboratory Parameters
timeFrame: From the start of study drug administration up to end of follow-up period, assessed up to Day 85
measure: Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations
timeFrame: From the start of study drug administration up to end of follow-up period, assessed up to Day 85
measure: Number of Participants Positive for Anti-drug Antibodies and With Neutralizing Antibodies for MEDI9929 at Any Visit
timeFrame: Days 1 (predose), 29, 57 and 85
Other outcomes:
Locations:
city: Kielce
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Rene van der Merwe, MBChB, MSc, FFPM
role: STUDY_DIRECTOR
References: