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

NCT02512900 | Completed Phase 1 Results

• 2 other identifiers: D5180C000022014-005450-19
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

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.

Conditions

Asthma

Keywords

Asthma

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (5)

• Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events

  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

  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

  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

  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

  Days 1 (predose), 29, 57 and 85

Study Arms (2)

MEDI9929, 140 mg, Cohort 1 (12 to 14 years)

EXPERIMENTAL

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

MEDI9929, 140 mg, Cohort 2 (15 to 17 years)

EXPERIMENTAL

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

Interventions

MEDI9929, 140 mg DRUG

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.

Also known as: Subcutaneous single-dose

MEDI9929, 140 mg, Cohort 1 (12 to 14 years); MEDI9929, 140 mg, Cohort 2 (15 to 17 years)

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead
• Amgen: collaborator

Study Sites (4)

Research Site

Kielce, 25-040, Poland

Location

Research Site

Lodz, 71-329, Poland

Location

Research Site

Wroclaw, 51-162, Poland

Location

Research Site

Wroclaw, 53-201, Poland

Location

MeSH Terms

Conditions

Asthma

Interventions

tezepelumab; Injections, Subcutaneous

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Rene van der Merwe, Senior Director, Clinical Development, Respiratory, and Inflammation
• Organization: MedImmune, LLC

301-398-0000

Study Officials

• Rene van der Merwe, MBChB, MSc, FFPM

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2015
• First Posted: July 31, 2015
• Study Start: September 10, 2015
• Primary Completion: May 17, 2016
• Study Completion: May 17, 2016
• Last Updated: June 21, 2017
• Results First Posted: February 23, 2017

Record last verified: 2017-05

Locations

PL (4)