A Study to Assess the Efficacy, Safety, and Tolerability of CAT-354 in Subjects With Asthma

A Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of CAT-354

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

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Other: Placebo; Biological: CAT-354 1 mg/kg; Biological: CAT-354 5 mg/kg; Other: CAT-354 10 mg/kg

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincents Hospital, Thoracic Medicine Unit
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Respiratory Medicine Department, Mater Adult Hospital,
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandria Hospital, Dept of Respiratory Medicine
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Clinical Research Unit
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre, Dept Respiratory Medicine.
    • Footscray, Victoria, Australia, 3011
      • Dep of Respiratory & Sleep Medicine, Western Hospital
    • Parkville, Victoria, Australia, 3050
      • Respiratory & Sleep Medicine, Royal Melbourne Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Lung Institute WA, Sir Charles Gardner Hospital
    • Nedlands, Western Australia, Australia, 6009
      • WA Lung Research, Sir Charles Gairdner Hospital
• Germany
  • Berlin, Germany, 13125
    • Evangelische Lungenklinik Berlin - Kardiologie/Pneumologie - 1.OG, Haus 23
  • Berlin, Germany, D-13353
    • Med. Klinik m. S. Infektiologie und Pneumologie, Charite - Universitätsmedizin Berlin
  • Bonn, Germany, 53123
    • Lungen und Bronchialheikunde
  • Bonn, Germany, 53123
    • Praxis für Lungen-und Bronchialheilkunde, Allergologie und Umweltmedizin
  • Bonn, Germany, 53127
    • Rheinische Friedrich-Wilhelms-Universität, Medizinische Klinik und Poliklinik II, Innere Medizin
  • Frankfurt, Germany, 60596
    • Internistisches Facharztzentrum Stresemannallee
  • Magdeburg, Germany, 39120
    • Universitätsklinikum Magdeburg Fachbereich Pneumologie
  • Mainz, Germany, 55131
    • Universitätsklinikum Mainz, Klinische Forschung Pneumologie, III. med. Klinik
  • Munster, Germany, 48149
    • Universitätsklinikum Münster Klinik und Poliklinik für Dermatologie
  • Rostock, Germany, 18057
    • Universität Rostock, Medizinische Fakultät Klinik und Poliklinik für Innere Medizin
  • Treuenbrietzen, Germany, 14929
    • Johanniter-Krankenhaus im Fläming gGmbH, Pneumologie
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
• Poland
  • Bialystok, Poland, 15-025
    • Prywatny Gabinet Internistyczno-Alergologiczny
  • Białystok, Poland, 15-003
    • ISPL Centrum Medyczne
  • Katowice, Poland, 40-752
    • Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej Akademii Medycznej, Klinika Pneumologii
  • Kraków, Poland, 31-159
    • Niepubliczny Zakład Opieki Zdrowotnej Atopia
  • Lubin, Poland, 59-300
    • Szpital ZOZ Lubin Oddzial Alergologiczny i Chorob Wewnetrznych
  • Lublin, Poland, 20-093
    • Wojewodzki Szpital Specjalistyczny, Poradnia Alergologiczna
  • Lublin, Poland, 20-607
    • Alergopneuma Przychodnia Alergologiczno-Pulmonologiczna Marek Michnar i wsp.
  • Warszawa, Poland, 01-138
    • Instytut Gruzlicy i Chorob Pluc
  • Zgierz, Poland, 95-100
    • Wojewódzki Szpital Specjalistyczny w Zgierzu
  • Łódź, Poland, 91-153
    • Uniwersytecki Szpital Kliniczny nr 1 Im. Norberta Barlickiego w Łodzi
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Glasgow, United Kingdom, G12 OYN
    • Gartnavel General Hospital
  • Leicester, United Kingdom, LE3 9QP
    • University Hospitals of Leicester NHS Trust, Glenfield Hospital
  • London, United Kingdom, SW3 6HP
    • Royal Brompton Hospital
  • Manchester, United Kingdom, M23 9LT
    • University Hospital of South Manchester NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Newport, United Kingdom, NP20 2UB
    • Royal Gwent Hospital
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk and Norwich University Hospital
  • Stevenage, Hertfordshire, United Kingdom, SG1 4AB
    • Lister Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.	Other: Placebo; Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.; Other Names: Tralokinumab
Experimental: CAT-354 1 mg/kg; CAT-354 1 milligram per kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Biological: CAT-354 1 mg/kg; CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.; Other Names: Tralokinumab
Experimental: CAT-354 5 mg/kg; CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Biological: CAT-354 5 mg/kg; CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.; Other Names: Tralokinumab
Experimental: CAT-354 10 mg/kg; CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56	Other: CAT-354 10 mg/kg; CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Doubling Concentration of Methacholine at Day 28	Change in doubling concentrations of methacholine was calculated as Log2 PC20 (Visit x) - Log2 PC20 (Baseline), where x was the post-baseline assessment (Day 28) and PC20 was provocative concentration of methacholine causing 20 percent fall in forced expiratory volume in 1 second (FEV1). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Change in doubling concentration was summarized for sub-therapeutic dose (placebo and CAT-354 1 milligram/kilogram [mg/kg]) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.	Baseline and Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination	Change in doubling concentrations of methacholine was calculated as Log2 PC20 (Visit x) - Log2 PC20 (Baseline), where x was the post-baseline assessment (Day 28) and PC20 was provocative concentration of methacholine causing 20 percent fall in forced expiratory volume in 1 second (FEV1). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Change in doubling concentration was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.	Baseline, Day 56, 84 or early termination (any time before Day 84)
Forced Expiratory Volume in 1 Second (FEV1)	The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.	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)
Forced Vital Capacity (FVC)	The FVC was volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.	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)
Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC)	Percentage of FEV1 was calculated as (FEV1/FVC)*100. It signified the percentage of the total amount of air exhaled from the lungs during the first second of forced exhalation. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Result was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.	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)
Asthma Control Questionnaire (ACQ) Total Score	The ACQ is questionnaire that comprises of 7-questions evaluating participant's asthma control. Six self-administered questions assess asthma control over the past week covering nocturnal waking, morning symptoms, activity limitations, shortness of breath, wheezing, and short-acting bronchodilator use; using 7-point ordinal rating scale from 0 (good control) to 6 (poor control). Seventh question is completed by a health professional on forced expiratory volume in 1 second (FEV1) percentage (%) predicted; scale: 0 (greater than [>] 95% predicted) to 6 (less than [<] 50% predicted. Final score is the average score of the 7 questions, with a score range of 0 (well controlled) to 6 (extremely poor controlled). Result was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.	Baseline, Day 28, 56, 84 or early termination (any time before Day 84)
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.	Day 0 to 84
Number of Participants With Diary Data	Participants recorded asthma symptoms, use of reliever inhalers (beta-agonist use for symptom relief and as prophylaxis), and morning and evening peak expiratory flow (PEF) measurements in a diary.	Day 0, 4, 14, 28, 35, 56, 63 to Day and 84
Number of Participants With Exacerbations	Exacerbation was defined as: Mild (determined from diary data) - 2 consecutive days satisfying the same or 1 of the following criteria: any night with awakening(s) due to asthma or morning PEF 20 % or more below baseline where baseline = average of the 10 days before randomization or as-needed medication use of 2 inhalations or more in 24 hours above baseline where baseline = average of the 10 days before randomization. Severe (determined by taking an exacerbation update and history): deterioration of asthma resulting in emergency treatment or hospitalization or need for oral steroids for 3 days or more (as judged by the Investigator).	Day 0 to Day 84
Morning Peak Flow and Peak Flow Variability	Peak flow is a participant's maximum speed of expiration.	Day 0 to Day 84
Adult Asthma Quality of Life (QoL) Questionnaire Final Score	The AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants are asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean response to all questions. The 4 domain scores are the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment).	Day 0, 28, 84 or early termination (any time before Day 84)
Maximum Observed Serum Concentration (Cmax) for CAT-354		Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Minimum Observed Serum Concentration (Cmin) for CAT-354		Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354		Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Accumulation Ratio for CAT-354 (RA)	Accumulation ratio (RA) is calculated for Cmax, Cmin and AUC as RA for Cmax = Cmax (56 - 84)/Cmax (0 - 28); Similarily, RA for Cmin = Cmin (56 - 84)/Cmin (0 - 28) and RA for AUC= AUC (56 - 84)/AUC (0 - 28) where Cmax (0 - 28) and Cmax (56 - 84) are the maximum observed serum concentration after first dose (Day 0 to Day 28) and after third dose (Day 56 to Day 84), respectively; Cmin (0 - 28) and Cmin (56 - 84) are the minimum observed serum concentration after first and third dose, respectively; AUC (0 - 28) and AUC (56 - 84) are the area under the serum concentration time curve over a dosage interval determined after first and third dose, respectively.	Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 84 that were absent before treatment or that worsened relative to pre-treatment state.	Day 0 to 84

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: PRA Health Sciences; Cambridge Antibody Technology
• Investigators: Study Director: Thomas Mayer, M.D., PRA Health Sciences

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: March 13, 2008
• First Submitted That Met QC Criteria: March 19, 2008
• First Posted (Estimate): March 20, 2008

Study Record Updates

• Last Update Posted (Estimate): January 31, 2017
• Last Update Submitted That Met QC Criteria: December 7, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Asthma; Tralokinumab; CAT-354
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAT-354-0603; 2007-002090-31 (EudraCT Number)