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A Study to Assess Pharmacokinetics, Safety and Tolerability of Multiple Doses of CAT-354 in Subjects With Moderate Asthma

This study has been terminated.
(Study recruitment was terminated before the planned number of subjects was enrolled in CAT-354 10 mg/kg group due to the slow recruitment rate.)
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00974675
First received: September 8, 2009
Last updated: March 22, 2017
Last verified: March 2017
  Purpose
The study includes participants with moderate asthma who were randomly assigned to receive the study medication (CAT-354) or placebo.

Condition Intervention Phase
Moderate Asthma Biological: CAT-354 1mg/kg Biological: CAT-354 5 mg/kg Biological: CAT-354 10mg/kg Other: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo Controlled Study to Assess the Pharmacokinetics, Safety and Tolerability of Multiple Intravenous Doses of 3 Dose Levels of CAT-354 in Subjects With Moderate Asthma

Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]
  • Maximum Observed Serum Concentration (Cmax) for CAT-354 After Second Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 28; Day 35 ]
  • Maximum Observed Serum Concentration (Cmax) for CAT-354 After Third Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 56; Day 63, 84, 105 and 147 ]
  • Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - t]) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]
  • Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - Infinity]) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]
    AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).

  • Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]
    Terminal elimination phase half-life is the time measured for the serum concentration to decrease by one half.

  • Clearance (CL) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]
    Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance was normalized by the body weight of the participant.

  • Volume of Distribution (Vd) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]
    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Volume of distribution was normalized to the body weight of the participant.

  • Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose [ Time Frame: Pre-dose on Day 28 ]
  • Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose [ Time Frame: Pre-dose on Day 56 ]
  • Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose [ Time Frame: Day 84 ]
  • Accumulation Ratio (R0) for CAT-354 [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0 and 56; Pre-dose on Day 28; Day 4, 7, 14, 21, 63 and 84 ]
    Accumulation ratio is calculated as: R0 = AUC(56 - 84)/AUC(0 - 28) where AUC(0 - 28) and AUC(56 - 84) are the area under the serum concentration time curve over a dosage interval determined after the first dose (Day 0 to Day 28) and after the third dose (Day 56 to Day 84), respectively.


Secondary Outcome Measures:
  • Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 0 to Day 147 ]
    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 147 that were absent before treatment or that worsened relative to pre-treatment state.


Enrollment: 23
Actual Study Start Date: September 29, 2006
Study Completion Date: August 3, 2007
Primary Completion Date: August 3, 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CAT-354 1 mg/kg
CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Biological: CAT-354 1mg/kg
CAT-354 1 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Other Name: Tralokinumab
Experimental: CAT-354 5 mg/kg
CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Biological: CAT-354 5 mg/kg
CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Other Name: Tralokinumab
Experimental: CAT-354 10mg/kg
CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Biological: CAT-354 10mg/kg
CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Other Name: Tralokinumab
Placebo Comparator: Placebo
Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.
Other: Placebo
Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.

Detailed Description:
This study is a randomized, double-blind, placebo controlled study. Following confirmation of eligibility, subjects with moderate asthma will be recruited sequentially to one of three dose groups and randomly assigned within dose group to either CAT-354 or placebo. Doses of the assigned treatment will be administered on three occasions 28 days apart. Follow up for pharmacokinetic blood sampling and safety will continue to Day 147 post-first dose (91 days post-third dose).
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or infertile females
  • Subjects with asthma, well controlled on inhaled corticosteroid and taken as required (PRN) short acting beta 2 agonist therapy only
  • Unchanged dose of inhaled corticosteroid for 3 months prior to Day 0 and no expected need for change in dose during study
  • Forced expiratory volume in 1 second (FEV1) greater than or equal to 80% predicted at Screening (Baseline)
  • 18-60 years
  • General Practitioner diagnosis of asthma of 1 year's minimum duration (with respect to Day 0)
  • No significant abnormality on clinical examination or medical history (excluding atopic skin signs, symptoms and history)
  • 12-lead electrocardiogram with no clinical significant abnormality
  • Clinical chemistry hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator
  • A negative screen for drugs of abuse and alcohol
  • Body weight between 50-120 kg
  • Subjects aged between 18-40 years inclusive must have body mass index (BMI) 18-32 kilogram per square meter (kg/m^2) inclusive. Subjects aged between 41-60 years must have BMI between 18-30 kg/m^2 inclusive.

Exclusion Criteria:

  • Active concomitant disease, with exception of eczema
  • Expected onset of seasonal allergy before the administration of the last dose of study medication
  • History of severe exacerbation within 3 years of Day 0
  • Recorded use of inhaled short acting beta 2 agonist medication for symptoms within 14 days of Day 0 of: More than 6 doses per day on any 1 day or more than 3 doses per day on 6 or more days
  • Any medication other than: inhaled short-acting beta 2 agonist, inhaled corticosteroids, topic eczema treatments (with the exception of fluorinated corticosteroid, dermatological preparations which are not permitted), hormone replacement therapy, vitamin preparation/food supplements, occasional use of proton pump inhibitors, ranitidine, cimetidine, antacids or over-the-counter analgesics
  • Treatment within 6 months of Day 0 with any of the following: methylxanthines, inhaled cromones, leukotriene modifiers, anti- immunoglobulin E (IgE), anticholinergics, ketotifen, oral short acting B2 agonists, long-acting B2 agonists, oral or injected corticosteroids
  • Treatment of atopic symptoms, other than eczema, within 4 weeks of Day 0
  • History of medication that might carry-over effects into the study
  • Previously received monoclonal antibody, or a similar related protein, that might sensitize to CAT-354
  • Participation in another study within three months of the start of the study or 5 half lives of the previously administered investigational medicinal product (IMP), whichever is longer
  • Lower respiratory tract infection within 4 weeks of Day-14
  • Any acute illness in the two weeks before Day 0
  • Current smokers, those who have smoked in previous year, and those with smoking history of greater than or equal to 10 pack years
  • Considered by the investigator to be at risk of transmitting, through blood, the agents responsible for infectious diseases
  • Blood donation (550 ml) in the previous 2 months
  • Excessive intake of alcohol (more than 21 units a week for females or 28 units a week for males)
  • The subject's general practitioner has suggested a reason the subject should not participate in the study
  • The Investigator considers the subject should not take part for any reason.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00974675

Locations
United Kingdom
Chiltern International Limited
Slough, Berkshire, United Kingdom, SL1 2AD
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: MedImmune LLC MedImmune LLC
  More Information

Publications:
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00974675     History of Changes
Other Study ID Numbers: CAT-354-0602
2006-003199-36 ( EudraCT Number )
Study First Received: September 8, 2009
Results First Received: March 22, 2017
Last Updated: March 22, 2017

Keywords provided by MedImmune LLC:
Asthma
CAT-354
Tralokinumab

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on August 17, 2017