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

NCT00640016 | Terminated Phase 2 Results

• 2 other identifiers: CAT-354-06032007-002090-31
• Study Type: interventional
• Target: 14
• Locations: 5 countries
• Sites: 41

Brief Summary

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

Conditions

Asthma

Keywords

Asthma; CAT-354; Tralokinumab

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination

  Baseline, Day 56, 84 or early termination (any time before Day 84)

• Forced Expiratory Volume in 1 Second (FEV1)

  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)

  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)

  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

  Baseline, Day 28, 56, 84 or early termination (any time before Day 84)

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.

Other: Placebo

CAT-354 1 mg/kg

EXPERIMENTAL

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 5 mg/kg

EXPERIMENTAL

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 10 mg/kg

EXPERIMENTAL

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

Interventions

Placebo OTHER

Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.

Also known as: Tralokinumab

Placebo

CAT-354 1 mg/kg BIOLOGICAL

CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 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 60 minutes on Day 0, 28 and 56.

Also known as: Tralokinumab

CAT-354 5 mg/kg

CAT-354 10 mg/kg OTHER

CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

CAT-354 10 mg/kg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• MedImmune LLC: lead
• Cambridge Antibody Technology: collaborator
• PRA Health Sciences: collaborator

Study Sites (41)

St. Vincents Hospital, Thoracic Medicine Unit

Darlinghurst, New South Wales, 2010, Australia

Location

Respiratory Medicine Department, Mater Adult Hospital,

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandria Hospital, Dept of Respiratory Medicine

Woolloongabba, Queensland, 4102, Australia

Location

Eastern Clinical Research Unit

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre, Dept Respiratory Medicine.

Clayton, Victoria, 3168, Australia

Location

Dep of Respiratory & Sleep Medicine, Western Hospital

Footscray, Victoria, 3011, Australia

Location

Respiratory & Sleep Medicine, Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Lung Institute WA, Sir Charles Gardner Hospital

Nedlands, Western Australia, 6009, Australia

Location

WA Lung Research, Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Evangelische Lungenklinik Berlin - Kardiologie/Pneumologie - 1.OG, Haus 23

Berlin, 13125, Germany

Location

Med. Klinik m. S. Infektiologie und Pneumologie, Charite - Universitätsmedizin Berlin

Berlin, D-13353, Germany

Location

Lungen und Bronchialheikunde

Bonn, 53123, Germany

Location

Praxis für Lungen-und Bronchialheilkunde, Allergologie und Umweltmedizin

Bonn, 53123, Germany

Location

Rheinische Friedrich-Wilhelms-Universität, Medizinische Klinik und Poliklinik II, Innere Medizin

Bonn, 53127, Germany

Location

Internistisches Facharztzentrum Stresemannallee

Frankfurt, 60596, Germany

Location

Universitätsklinikum Magdeburg Fachbereich Pneumologie

Magdeburg, 39120, Germany

Location

Universitätsklinikum Mainz, Klinische Forschung Pneumologie, III. med. Klinik

Mainz, 55131, Germany

Location

Universitätsklinikum Münster Klinik und Poliklinik für Dermatologie

Münster, 48149, Germany

Location

Universität Rostock, Medizinische Fakultät Klinik und Poliklinik für Innere Medizin

Rostock, 18057, Germany

Location

Johanniter-Krankenhaus im Fläming gGmbH, Pneumologie

Treuenbrietzen, 14929, Germany

Location

Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

ISPL Centrum Medyczne

Bialystok, 15-003, Poland

Location

Prywatny Gabinet Internistyczno-Alergologiczny

Bialystok, 15-025, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej Akademii Medycznej, Klinika Pneumologii

Katowice, 40-752, Poland

Location

Niepubliczny Zakład Opieki Zdrowotnej Atopia

Krakow, 31-159, Poland

Location

Uniwersytecki Szpital Kliniczny nr 1 Im. Norberta Barlickiego w Łodzi

Lodz, 91-153, Poland

Location

Szpital ZOZ Lubin Oddzial Alergologiczny i Chorob Wewnetrznych

Lubin, 59-300, Poland

Location

Wojewodzki Szpital Specjalistyczny, Poradnia Alergologiczna

Lublin, 20-093, Poland

Location

Alergopneuma Przychodnia Alergologiczno-Pulmonologiczna Marek Michnar i wsp.

Lublin, 20-607, Poland

Location

Instytut Gruzlicy i Chorob Pluc

Warsaw, 01-138, Poland

Location

Wojewódzki Szpital Specjalistyczny w Zgierzu

Zgierz, 95-100, Poland

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Gartnavel General Hospital

Glasgow, G12 OYN, United Kingdom

Location

University Hospitals of Leicester NHS Trust, Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6HP, United Kingdom

Location

University Hospital of South Manchester NHS Foundation Trust

Manchester, M23 9LT, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Royal Gwent Hospital

Newport, NP20 2UB, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

Location

Lister Hospital

Stevenage, Hertfordshire, SG1 4AB, United Kingdom

Location

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

Study was prematurely terminated due to low recruitment rate, delay due to temporary halt and potential for expiry date of study drug. It was not considered possible to draw meaningful conclusions from the small dataset.

Results Point of Contact

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

jainm@medimmune.com

301-398-0000

Study Officials

• Thomas Mayer, M.D.

  PRA Health Sciences

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2008
• First Posted: March 20, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: January 31, 2017
• Results First Posted: January 31, 2017

Record last verified: 2016-12

Locations

DE (11); PL (10); NL (1); GB (10); AU (9)