Clinical trial NCT00640016: A Study to Assess the Efficacy, Safety, and Tolerability of CAT-354 in Subjects With Asthma
Official title: A Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of CAT-354
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
CAT-354
Tralokinumab
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: Cambridge Antibody Technology
name: PRA Health Sciences
First posted: 2008-03-20
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the effects of CAT-354 on airway hyper-responsiveness (AHR) in uncontrolled asthma.

Detailed description: This is a randomized, stratified, double-blind, placebo-controlled, multicenter, multinational study in subjects with uncontrolled asthma despite optimal treatment. Following confirmation of eligibility, subjects will be randomly assigned on Day 0, to 1 of 4 dose groups 1 mg/kg CAT-354, 5 mg/kg CAT-354, 10 mg/kg CAT or Placebo to match all doses of CAT-354. Doses of the assigned treatment will be administered on three occasions 28 days apart. Subjects will be assessed for efficacy, including airway hyper-responsiveness (AHR), safety, pharmacokinetic, pharmacodynamics and immunogenicity until Day 84 post-first dose.

Eligibility criteria: Inclusion Criteria:

* Signed and dated written informed consent is obtained prior to any study related procedure taking place
* Women either infertile (example \[e.g.\], hysterectomized, sterile or post-menopausal with amenorrhea of least 1 year duration) or who are practicing an acceptable form of birth control
* Uncontrolled (refractory) asthma despite treatment with a minimum dose of 800 microgram (mcg) beclomethasonedipropionate or equivalent inhaled corticosteroid per day plus 1 or more additional controller, that is, long-acting beta-agonist, leukotriene antagonist or theophylline. Oral corticosteroids (not parenteral) as additional treatment at any dose are acceptable
* A forced expiratory volume in 1 second (FEV1) acceptable for airway hyper-responsiveness (AHR) challenge tests (greater than 60 percent of predicted normal) on the challenge days
* A provocative concentration of methacholine causing a 20 percent fall in FEV1 (PC20) less than 4 milligram per milliliter (mg/mL)
* Aged 18-80 years
* A 12-lead electrocardiogram (ECG) with no-clinically significant abnormalities
* Clinical chemistry, hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator
* Body weight of less than 130 kilogram (kg)
* No other clinically significant abnormality on history and clinical examination
* Able to comply with the requirements of the protocol.

Exclusion Criteria:

* Experienced a severe exacerbation within 28 days preceding Day -28/-14 to Day 0
* Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Day -28/-14 to Day 0
* Subjects with a history of allergic rhinitis, seasonal allergy or esophagitis must be optimally controlled and remain on a stable treatment regimen during the study
* Participation in another study within 5 half-lives or 3 months of the start of this study, whichever is the longer
* Lower respiratory tract infection within 6 weeks of Day -28/-14 to Day 0
* Current smokers or ex-smokers with greater than 10 pack-years
* Blood donation (more than 550 mL) in the previous 2 months
* Excessive intake of alcohol (as judged by the Investigator) or evidence of drug or solvent abuse
* Subjects with a physician-diagnosis of any other significant lung disease, including a primary diagnosis of chronic obstructive pulmonary disease or bronchiectasis, or lung cancer, sarcoidosis, tuberculosis, pulmonary fibrosis and cystic fibrosis
* Concurrent medication from Day -28/-14 to Day 0 (Screening visit) and for the duration of the study with any of the prohibited medications
* Significant, uncontrolled disease including serious psychological disorders, chronic renal failure, uncontrolled hypertension
* systolic blood pressure greater than 200 millimeters of mercury (mmHg), or diastolic blood pressure greater than 100 mmHg, heart disease, psoriasis requiring treatment and subjects who have had a heart attack or stroke within the 3 months preceding Day -28/-14 to Day 0, or who have a known aneurysm
* Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Day -28/-14 to Day 0
* Subjects with a history of allergic rhinitis, seasonal allergy or esophagitis must be optimally controlled and remain on a stable treatment regimen during the study
* Any factor which, in the opinion of the Investigator, would jeopardize the evaluation or safety or be associated with poor adherence to the protocol (that is, inability to complete study diary, perform peak expiratory flow (PEF) measurements)
* The subject's primary care physician recommends the subject should not take part in the study
* Known hypersensitivity to CAT-354 or its components, to the challenge agents used in the study or to related drugs.

Primary outcomes:
measure: Change From Baseline in Doubling Concentration of Methacholine at Day 28
timeFrame: Baseline and Day 28
Secondary outcomes:
measure: Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination
timeFrame: Baseline, Day 56, 84 or early termination (any time before Day 84)
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84)
measure: Forced Vital Capacity (FVC)
timeFrame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84)
measure: Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC)
timeFrame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, Day 63, 84 or early termination (any time before Day 84)
measure: Asthma Control Questionnaire (ACQ) Total Score
timeFrame: Baseline, Day 28, 56, 84 or early termination (any time before Day 84)
measure: Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Day 0 to 84
measure: Number of Participants With Diary Data
timeFrame: Day 0, 4, 14, 28, 35, 56, 63 to Day and 84
measure: Number of Participants With Exacerbations
timeFrame: Day 0 to Day 84
measure: Morning Peak Flow and Peak Flow Variability
timeFrame: Day 0 to Day 84
measure: Adult Asthma Quality of Life (QoL) Questionnaire Final Score
timeFrame: Day 0, 28, 84 or early termination (any time before Day 84)
measure: Maximum Observed Serum Concentration (Cmax) for CAT-354
timeFrame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
measure: Minimum Observed Serum Concentration (Cmin) for CAT-354
timeFrame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
measure: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354
timeFrame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
measure: Accumulation Ratio for CAT-354 (RA)
timeFrame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 0 to 84
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St. Vincents Hospital, Thoracic Medicine Unit
state: New South Wales
city: South Brisbane
country: Australia
facility: Respiratory Medicine Department, Mater Adult Hospital,
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandria Hospital, Dept of Respiratory Medicine
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre, Dept Respiratory Medicine.
state: Victoria
city: Footscray
country: Australia
facility: Dep of Respiratory & Sleep Medicine, Western Hospital
state: Victoria
city: Parkville
country: Australia
facility: Respiratory & Sleep Medicine, Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Lung Institute WA, Sir Charles Gardner Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: WA Lung Research, Sir Charles Gairdner Hospital
state: Western Australia
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin - Kardiologie/Pneumologie - 1.OG, Haus 23
city: Berlin
country: Germany
facility: Med. Klinik m. S. Infektiologie und Pneumologie, Charite - Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: Lungen und Bronchialheikunde
city: Bonn
country: Germany
facility: Praxis für Lungen-und Bronchialheilkunde, Allergologie und Umweltmedizin
city: Bonn
country: Germany
facility: Rheinische Friedrich-Wilhelms-Universität, Medizinische Klinik und Poliklinik II, Innere Medizin
city: Frankfurt
country: Germany
facility: Internistisches Facharztzentrum Stresemannallee
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg Fachbereich Pneumologie
city: Mainz
country: Germany
facility: Universitätsklinikum Mainz, Klinische Forschung Pneumologie, III. med. Klinik
city: Munster
country: Germany
facility: Universitätsklinikum Münster Klinik und Poliklinik für Dermatologie
city: Rostock
country: Germany
facility: Universität Rostock, Medizinische Fakultät Klinik und Poliklinik für Innere Medizin
city: Treuenbrietzen
country: Germany
facility: Johanniter-Krankenhaus im Fläming gGmbH, Pneumologie
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Bialystok
country: Poland
facility: Prywatny Gabinet Internistyczno-Alergologiczny
city: Białystok
country: Poland
facility: ISPL Centrum Medyczne
city: Katowice
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej Akademii Medycznej, Klinika Pneumologii
city: Kraków
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej Atopia
city: Lubin
country: Poland
facility: Szpital ZOZ Lubin Oddzial Alergologiczny i Chorob Wewnetrznych
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny, Poradnia Alergologiczna
city: Lublin
country: Poland
facility: Alergopneuma Przychodnia Alergologiczno-Pulmonologiczna Marek Michnar i wsp.
city: Warszawa
country: Poland
facility: Instytut Gruzlicy i Chorob Pluc
city: Zgierz
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Zgierzu
city: Łódź
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 1 Im. Norberta Barlickiego w Łodzi
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust, Glenfield Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester NHS Foundation Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Newport
country: United Kingdom
facility: Royal Gwent Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Stevenage, Hertfordshire
country: United Kingdom
facility: Lister Hospital
Study officials:
affiliation: PRA Health Sciences
name: Thomas Mayer, M.D.
role: STUDY_DIRECTOR
References: