Clinical trial NCT00873860: Study to Evaluate the Safety and Efficacy of CAT-354
Official title: A Phase 2a, Randomized, Double-blind, Placebo-Controlled, Parallel-Arm, Multicenter Study to Evaluate the Efficacy and Safety of CAT-354, a Recombinant Human Monoclonal Antibody Directed Against Interleukin-13 (IL-13), on Asthma Control in Adults With Uncontrolled, Moderate-to-severe, Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: CAT-354
Tralokinumab
Asthma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2009-04-02
Enrollment: 357
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel-arm study to evaluate the efficacy and safety of 3 subcutaneous (SC) treatment regimens of CAT-354 in adult subjects with uncontrolled, moderate-to-severe, persistent asthma.

Detailed description: Study MI-CP199, a Phase 2a, randomized, double-blind, placebo-controlled, parallel-arm, multicenter study will evaluate the effect of 3 SC treatment regimens of CAT-354 on asthma control in adults with uncontrolled, moderate-to-severe, persistent asthma.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects
* Age 18 to 65 years at the time of Screening
* Subjects must have a body mass index (BMI) between 18 and 40 kilogram per square meter (kg/m\^2)
* Written informed consent obtained from the subject prior to performing any protocol related procedures, including Screening evaluations
* Physician-diagnosed moderate-to-severe, persistent asthma requiring treatment with appropriate asthma controller medication
* Shows forced expiratory volume in 1 second (FEV1) reversibility postbronchodilator of greater than or equal to (\>=)12 percent and \>=200 milliliter (mL) or have shown such values in a previous test within the last year, or have a positive airway hyperresponsiveness (AHR) test result in the last year
* Pre-bronchodilator FEV 1 value \>=40 percent of individual predicted value at Visits 1 and 3
* Uncontrolled asthma consistent with Expert Panel Report (EPR)-3. In the 2 to 4 weeks preceding Screening, subjects should have a history of 1 or more of the following: Daytime asthma symptoms \>=2 days/week, Nighttime awakening \>=1 night/week, Salbutamol use \>=2 days/week
* An Asthma control questionnaire (ACQ) score \>=1.5 at Visits 1 and 3
* At least 1 occurrence of asthma exacerbation in the past year that required an unscheduled medical encounter
* Men, unless surgically sterile, must likewise practice 2 effective methods of birth control (condom with spermicide) and must use such precautions from Day 1 through Study Day 169
* Otherwise healthy by medical history and physical examination for that age group
* A chest x-ray or computed tomography (CT) scan within the previous 12 months with no findings suggestive of acute or chronic respiratory pathology other than asthma
* Ability and willingness to complete the follow-up period until Day 169 as required by the protocol.

Exclusion Criteria:

* Known history of allergy or reaction to any component of the investigational product formulation
* Acute illness other than asthma at the start of the study
* History of an active infection within 4 weeks prior to Screening, or evidence of clinically significant active infection, including ongoing chronic infection
* History of ingestion of untreated water in a location known to be infected with parasites, resulting in acute or chronic diarrhea; or a diagnosis of parasitic infection within 6 months prior to Screening
* Use of immunosuppressive medication (except oral prednisone up to 10 milligram/day (mg/day) and inhaled and topical corticosteroids) within 30 days before randomization into the study
* Receipt of immunoglobulin or blood products within 30 days before randomization into the study
* Receipt of any investigational drug therapy or use of any biologicals including omalizumab within 6 months before the first dose of investigational product in this study or within 5 half-lives of an investigational agent or biologic, whichever is longer
* History of any known immunodeficiency disorder
* A positive hepatitis B surface antigen, or hepatitis C virus antibody
* A positive human immunodeficiency virus test or is taking antiretroviral medications, as determined by medical history and/or subject's verbal report
* A live or attenuated vaccination received within 4 weeks prior to Screening
* Previous medical history, or evidence, of an intercurrent illness that may compromise the safety of the subject in the study
* History of clinically significant abnormality on electrocardiogram (ECG) in the opinion of the investigator
* Lactation (women)
* History of treatment for alcohol or drug abuse within the past year
* History suggestive of chronic obstructive pulmonary disease (COPD) and of cigarette smoking \>=10 pack-years
* Evidence of any systemic disease on physical examination
* History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy less than or equal to (\<=)1 year prior to Study Day 1 or other malignancies treated with apparent success with curative therapy \<=5 years prior to entry
* Known exposure to inhaled occupational agents or fumes
* Any condition (eg, cystic fibrosis \[CF\] or COPD) that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of study results
* Individuals who are legally institutionalized
* Employees of the clinical study site or any other individuals involved with the conduct of the study, or family members of such individuals.

Primary outcomes:
measure: Change From Baseline in the Mean Asthma Control Questionnaire (ACQ) Score at Day 92
timeFrame: Day 1 and 92
Secondary outcomes:
measure: Time to First Observed Asthma Control
timeFrame: Day 1 to Day 92 and Day 169
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites at Day 1, 15, 29, 43, 57, 71, 85, 92, 127 and 169
timeFrame: Day 1, 15, 29, 43, 57, 71, 85, 92, 127 and 169
measure: Change From Baseline in Peak Expiratory Flow (PEF) Recorded at Home Every Week From Day 1 to 169
timeFrame: Day -7 to 1 (predose), Day 2 to 169
measure: Number of Puffs of Rescue Beta-2 Agonist Per Week
timeFrame: Day -7 to 169
measure: Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores
timeFrame: Day 1, 29, 57, 92, 127 and 169
measure: Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores at Day 29, 57, 92, 127 and 169
timeFrame: Day 1, 29, 57, 92, 127 and 169
measure: Patient Global Impression of Change (PGIC)
timeFrame: Day 92 and 169
measure: Percentage of Participants With Mean Asthma Control Questionnaire (ACQ) Score Less Than or Equal to 0.75 or ACQ Score Greater Than 0.75 But Less Than 1.5
timeFrame: Day 92 and 169
measure: Serum Concentration for CAT-354
timeFrame: Predose on Day 15, 29, 43, 57, 71 and 85; Day 88, 92, 99, 127, and 169
measure: Number of Participants With Anti-Drug Antibodies to CAT-354 at Any Visit
timeFrame: Day 1, 92 and 169
measure: Percentage of Participants With Positive Serum Antibodies to CAT-354 at Any Visit
timeFrame: Day 1, 92 and 169
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 to 169
measure: Percentage of Participants With at Least 1 Moderate or Severe Exacerbation
timeFrame: Day 92 and 169
measure: Moderate or Severe Asthma Exacerbations Per Person Per Annum
timeFrame: Day 1 to Day 92 and Day 169
measure: Time to First Moderate or Severe Asthma Exacerbation
timeFrame: Day 1 to Day 92 and Day 169
Other outcomes:
Locations:
city: Burgas
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Rousse
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sofia III
country: Bulgaria
facility: Research Site
city: Sofia II
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: Stara Zagora
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt/Main
country: Germany
facility: Research Site
city: Frankfurt/Main
country: Germany
facility: Research Site
city: Landsberg a. Lech
country: Germany
facility: Research Site
city: Lich
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Bielsko-Biala
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Pikary Slaskie
country: Poland
facility: Research Site
city: Skalskie
country: Poland
facility: Research Site
city: Warsazawa
country: Poland
facility: Research Site
city: Warszawa II
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Zabrze II
country: Poland
facility: Research Site
city: Zabrze
country: Poland
facility: Research Site
city: Zabrze
country: Poland
facility: Research Site
city: Arad
country: Romania
facility: Research Site
city: Arad
country: Romania
facility: Research Site
city: Arad
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Deva
country: Romania
facility: Research Site
city: Deva
country: Romania
facility: Research Site
city: Timisoara Timis
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Wythenshawe
country: United Kingdom
facility: Research Site
state: Manchester
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, She D, Kell C, May RD, Geba GP, Molfino NA. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013 Feb;41(2):330-8. doi: 10.1183/09031936.00223411. Epub 2012 Jun 27.
citation: Baverel PG, White N, Vicini P, Karlsson MO, Agoram B. Dose-Exposure-Response Relationship of the Investigational Anti-Interleukin-13 Monoclonal Antibody Tralokinumab in Patients With Severe, Uncontrolled Asthma. Clin Pharmacol Ther. 2018 May;103(5):826-835. doi: 10.1002/cpt.803. Epub 2017 Sep 28.
citation: Wilkes DS, Chew T, Flaherty KR, Frye S, Gibson KF, Kaminski N, Klemsz MJ, Lange W, Noth I, Rothhaar K. Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis. Eur Respir J. 2015 May;45(5):1393-402. doi: 10.1183/09031936.00105314. Epub 2015 Jan 22.