Clinical trial NCT02054130: Study to Evaluate the Efficacy and Safety of MEDI9929 (AMG 157) in Adult Subjects With Inadequately Controlled, Severe Asthma
Official title: A Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of MEDI9929 in Adult Subjects With Inadequately Controlled, Severe Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2014-02-04
Enrollment: 584
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the effect of 3 dose levels of MEDI9929 (AMG 157) on asthma exacerbations in adult subjects with inadequately controlled, severe asthma.


Eligibility criteria: Inclusion Criteria:

* Age 18 through 75
* Body mass index (BMI) between 18-40 kg/m2 and weight greater than or equal 40 kg
* Documented physician-diagnosed asthma - Subjects must have received a physician-prescribed asthma controller regimen with medium- or high-dose inhaled corticosteroids (ICS) plus long acting β2 agonist (LABA) -If on asthma controller medications in addition to ICS plus LABA, the dose of the other asthma controller medications (leukotriene receptor inhibitors, theophylline, secondary ICS, long-acting anti-muscarinics (LAMA), cromones, or maintenance oral prednisone or equivalent up to a maximum of 10 mg daily or 20 mg every other day for the maintenance treatment of asthma) must be stable. -Subjects must have a documented history of at least 2 asthma exacerbation events OR at least 1 severe asthma exacerbation resulting in hospitalization within the 12 months prior to first study visit.

Exclusion Criteria:

* Diagnosis of vocal cord dysfunction, reactive airways dysfunction syndrome, hyperventilation and panic attacks, or other mimics of asthma.
* Current smokers or subjects with a smoking history of ≥ 10 pack years
* Former smokers with \< 10 pack years must have stopped for at least 1 year to be eligible.
* Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of subject safety or study results (eg, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, bronchiectasis, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome).
* Evidence of active liver disease.
* History of Cancer, except for basal cell carcinoma or insitu carcinoma of the cervix treated with apparent success with curative therapy or other malignancies are eligible provided that curative therapy was completed -Known history of active tuberculosis (TB)
* History of anaphylaxis to any biologic therapy
* Positive medical history for hepatitis B or C
* Subject with human immunodeficiency virus (HIV) or subject taking antiretroviral medications, as determined by medical history and/or subject's verbal report.

Primary outcomes:
measure: Annualized Asthma Exacerbation Rate (AER) Through Week 52
timeFrame: Week 0 (Day 1) up to Week 52
Secondary outcomes:
measure: Reduction in AER on Subpopulations at Week 52
timeFrame: Week 52
measure: Change From Baseline in Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Week 52
timeFrame: Baseline (Week 0 [Day 1]) to Week 52
measure: Change From Baseline in FEV1 on Subpopulations at Week 52
timeFrame: Baseline and up to Week 52
measure: Change From Baseline in Post-bronchodilator (Post-BD) FEV1 and FVC at Week 52
timeFrame: Baseline (Week 0 [Day 1]) to Week 52
measure: Change From Baseline in Overall Symptoms Score on Subpopulations at Week 52
timeFrame: Baseline and up to Week 52
measure: Change From Baseline in Asthma Symptoms Measured by Asthma Daily Diary at Week 52
timeFrame: Baseline (Week 0 [Day 1]) and Week 52
measure: Change From Baseline in Asthma Symptoms Measured by Asthma Control Questionnaire (ACQ-6) Score at Week 52
timeFrame: Baseline (Week 0 [Day 1]) and Week 52
measure: Rate of Severe Asthma Exacerbation Through Week 52
timeFrame: Week 0 (Day 1) up to Week 52
measure: Time to First Asthma Exacerbation Through Week 52
timeFrame: Week 0 (Day 1) through Week 52
measure: Time to First Severe Asthma Exacerbation Through Week 52
timeFrame: Week 0 (Day 1) through Week 52
measure: Number of Participants With at Least One Asthma Exacerbations Through Week 52
timeFrame: Week 0 (Day 1) through Week 52
measure: Number of Participants With at Least One Severe Asthma Exacerbations Through Week 52
timeFrame: Week 0 (Day 1) through Week 52
measure: Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ [S]) Overall Score at Week 52
timeFrame: Baseline (Week 0 [Day 1]) and Week 52
measure: Change From Baseline in European Quality of Life-5 Dimensions 5 Level Version (EQ-5D-5L) Health State Evaluation at Week 52
timeFrame: Baseline (Week 0 [Day 1]) and Week 52
measure: Total Amount of Study Drug Exposure
timeFrame: Week 0 (Day 1) through Week 52
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 upto Week 64
measure: Number of Participants With TEAEs Related to Vital Sign Parameters
timeFrame: Day 1 upto Week 64
measure: Number of Participants With TEAEs Related to Clinical Laboratory Evaluation
timeFrame: Day 1 upto Week 64
measure: Number of Participants With TEAEs Related to Electrocardiogram Evaluations
timeFrame: From the start of study drug administration upto Week 64
measure: Mean Serum Concentrations of MEDI9929
timeFrame: Week 0 (Day 1) to Week 64
measure: Number of Participants With Positive Antibodies to MEDI9929
timeFrame: Week 0 (Day 1) to Week 64
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Oviedo
country: United States
facility: Research Site
state: Florida
city: Savannah
country: United States
facility: Research Site
state: Georgia
city: Peoria
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Dublin
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Rock Hill
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Velingrad
country: Bulgaria
facility: Research Site
city: Brandys nad Labem
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Mlada Boleslav
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Strakonice
country: Czechia
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Csorna
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Farkasgyepü
country: Hungary
facility: Research Site
city: Gödöllő
country: Hungary
facility: Research Site
city: Komarom
country: Hungary
facility: Research Site
city: Mateszalka
country: Hungary
facility: Research Site
city: Nagykanizsa
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Százhalombatta
country: Hungary
facility: Research Site
city: Torokbalint
country: Hungary
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar-Saba
country: Israel
facility: Research Site
city: Petach Tikva
country: Israel
facility: Research Site
city: Rehovot
country: Israel
facility: Research Site
city: Tel Hashomer
country: Israel
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fujisawa-shi
country: Japan
facility: Research Site
city: Kiyose-shi
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Maebashi-shi
country: Japan
facility: Research Site
city: Ora-gun
country: Japan
facility: Research Site
city: Sagamihara-shi
country: Japan
facility: Research Site
city: Saitama-Ken
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Taito-ku
country: Japan
facility: Research Site
city: Toshima-ku
country: Japan
facility: Research Site
city: Yokkaichi-shi
country: Japan
facility: Research Site
city: Daugavpils
country: Latvia
facility: Research Site
city: Rezekne
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Klaipeda
country: Lithuania
facility: Research Site
city: Klaipeda
country: Lithuania
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Sremska Kamenica
country: Serbia
facility: Research Site
city: Bardejov
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Ilava
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Nove Zamky
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Spisska Nova Ves
country: Slovakia
facility: Research Site
city: Sturovo
country: Slovakia
facility: Research Site
city: Surany
country: Slovakia
facility: Research Site
city: Topolcany
country: Slovakia
facility: Research Site
city: Zvolen
country: Slovakia
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Middelburg
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Mykolayiv
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Poltava
country: Ukraine
facility: Research Site
city: Suprunivka Vil., Poltava Regio
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, van der Merwe R. Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med. 2017 Sep 7;377(10):936-946. doi: 10.1056/NEJMoa1704064.
citation: Corren J, Pham TH, Garcia Gil E, Salapa K, Ren P, Parnes JR, Colice G, Griffiths JM. Baseline type 2 biomarker levels and response to tezepelumab in severe asthma. Allergy. 2022 Jun;77(6):1786-1796. doi: 10.1111/all.15197. Epub 2022 Feb 9.
citation: Corren J, Ambrose CS, Salapa K, Roseti SL, Griffiths JM, Parnes JR, Colice G. Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4334-4342.e6. doi: 10.1016/j.jaip.2021.07.045. Epub 2021 Aug 3.
citation: Ly N, Zheng Y, Griffiths JM, van der Merwe R, Agoram B, Parnes JR, Roskos L. Pharmacokinetic and Pharmacodynamic Modeling of Tezepelumab to Guide Phase 3 Dose Selection for Patients With Severe Asthma. J Clin Pharmacol. 2021 Jul;61(7):901-912. doi: 10.1002/jcph.1803. Epub 2021 Jan 16.
citation: Corren J, Garcia Gil E, Griffiths JM, Parnes JR, van der Merwe R, Salapa K, O'Quinn S. Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY. Ann Allergy Asthma Immunol. 2021 Feb;126(2):187-193. doi: 10.1016/j.anai.2020.10.008. Epub 2020 Oct 23.