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

NCT00974675 | Terminated Phase 1 Results

• 2 other identifiers: CAT-354-06022006-003199-36
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The study includes participants with moderate asthma who were randomly assigned to receive the study medication (CAT-354) or placebo.

Conditions

Moderate Asthma

Keywords

Asthma; CAT-354; Tralokinumab

Outcome Measures

Primary Outcomes (12)

• Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose

  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

  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

  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

  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

  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).

  Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21

• Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose

  Terminal elimination phase half-life is the time measured for the serum concentration to decrease by one half.

  Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21

• Clearance (CL) for CAT-354 After First Dose

  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.

  Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21

• Volume of Distribution (Vd) for CAT-354 After First Dose

  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.

  Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21

• Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose

  Pre-dose on Day 28

• Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose

  Pre-dose on Day 56

• Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose

  Day 84

• Accumulation Ratio (R0) for CAT-354

  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.

  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

Secondary Outcomes (1)

• Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  Day 0 to Day 147

Study Arms (4)

CAT-354 1 mg/kg

EXPERIMENTAL

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 5 mg/kg

EXPERIMENTAL

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 10mg/kg

EXPERIMENTAL

CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.

Biological: CAT-354 10mg/kg

Placebo

PLACEBO COMPARATOR

Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.

Other: Placebo

Interventions

CAT-354 1mg/kg BIOLOGICAL

CAT-354 1 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.

Also known as: Tralokinumab

CAT-354 1 mg/kg

CAT-354 5 mg/kg BIOLOGICAL

CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.

Also known as: Tralokinumab

CAT-354 5 mg/kg

CAT-354 10mg/kg BIOLOGICAL

CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.

Also known as: Tralokinumab

CAT-354 10mg/kg

Placebo OTHER

Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)
• 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)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (1)

Chiltern International Limited

Slough, Berkshire, SL1 2AD, United Kingdom

Location

Related Publications (1)

• Singh D, Kane B, Molfino NA, Faggioni R, Roskos L, Woodcock A. A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma. BMC Pulm Med. 2010 Jan 8;10:3. doi: 10.1186/1471-2466-10-3.

  PMID: 20064211 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

tralokinumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Limitations and Caveats

Recruitment to the study was terminated before the planned number of participants was enrolled in CAT-354 10 mg/kg group due to the slow recruitment rate.

Results Point of Contact

• Title: Meena Jain, MB BChir/Associate Medical Director
• Organization: MedImmune, LLC

jainm@medimmune.com

301-398-0000

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2009
• First Posted: September 10, 2009
• Study Start: September 29, 2006
• Primary Completion: August 3, 2007
• Study Completion: August 3, 2007
• Last Updated: May 2, 2017
• Results First Posted: May 2, 2017

Record last verified: 2017-03

Locations

GB (1)