A Study to Assess the Efficacy, Safety,and Tolerability of CAT-354

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00640016
• Other study ID #: CAT-354-0603
• Status: Terminated
• Phase: Phase 2
• First received: March 13, 2008
• Last updated: September 11, 2012
• Start date: March 2008
• Est. completion date: April 2009

Study information

• Verified date: September 2012
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesAustralia: National Health and Medical Research CouncilUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: April 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Signed and dated written informed consent is obtained prior to any study related procedure taking place.

• Women either infertile (e.g. hysterectomised, sterile or post menopausal with amenorrhoea of least one year duration) or who are practicing an acceptable form of birth control (contraceptive pill or double-barrier contraception - partner using condom and subject using spermicide, diaphragm, intra-uterine device or contraceptive sponge) for 1 month prior to Visit 1 (screening visit) or longer if requested by the investigator. Women of childbearing potential must continue to practice birth control during the study and for at least 2 months after completing the study. Women of childbearing potential must have a negative pregnancy test at screening and Visit 2, 5, 7 and 9.

• Uncontrolled (refractory) asthma despite optimal treatment - subjects will have Global Initiative for Asthma (GINA 2006) clinical features of uncontrolled asthma despite treatment with a minimum dose of 800 µg beclomethasone dipropionate or equivalent inhaled corticosteroid per day plus one or more additional controller i.e. long-acting b-agonist, leukotriene antagonist or theophylline. Oral corticosteroids (not parenteral) as additional treatment at any dose are acceptable. The dose of inhaled and oral corticosteroids must have been stable within 4 weeks preceding Visit 1 (screening visit) and will be expected to remain stable for the duration of the study. If subjects are on single inhaler combination products at Visit 1 (e.g. fluticasone/salmeterol - Advair®/Seretide® or Symbicort (budesonide/formoterol) SMART®) they must receive the two components as two separate inhaler medications for the purpose of the trial. This will facilitate withholding the long-acting b-agonist component before lung function and challenge testing (see Section 9.5.7). The GINA 2006 [14] levels of asthma control and treatment are described in Appendix 3.

• A forced expiratory volume in 1 second (FEV1) acceptable for AHR challenge tests (= 60% of predicted normal) on the challenge days.

• A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) = 4 mg/mL.

• Aged 18-80 years and are ambulatory and able to travel to the clinic.7. A 12-lead electrocardiogram (ECG) with no-clinically significant abnormalities.

• Clinical chemistry, haematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator.

• Body weight of =130 kg.

• No other clinically significant abnormality on history and clinical examination (see also Exclusion Criteria).

• Able to comply with the requirements of the protocol.

Exclusion Criteria:

• Experienced a severe exacerbation within 28 days preceding Visit 1.

• Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Visit 1. Subjects with a history of allergic rhinitis, seasonal allergy or oesophagitis must be optimally controlled and remain on a stable treatment regimen during the study.

• Participation in another study within five half lives or three months of the start of this study, whichever is the longer. This does not apply to methodological or observational studies in which no investigational medicinal product (IMP) was given.

• Lower respiratory tract infection within six weeks of Visit 1.5.

• Current smokers or ex-smokers with greater than 10 pack-years (number of pack years = (number of cigarettes per day/20) x number of years smoked, e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years).

• Blood donation (more than 550 mL) in the previous two 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 Visit 1 (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 > 200 mmHg, or diastolic blood pressure > 100 mmHg, heart disease, psoriasis requiring treatment and subjects who have had a heart attack or stroke within the 3 months preceding Visit 1, or who have a known aneurysm.

• Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Visit 1. Subjects with a history of allergic rhinitis, seasonal allergy or oesophagitis must be optimally controlled and remain on a stable treatment regimen during the study.

• Any factor which, in the opinion of the Investigator, would jeopardise the evaluation or safety or be associated with poor adherence to the protocol (i.e. inability to complete study diary, perform 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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• CAT-354
1 mg/kg CAT-354 on Day 0, 28, and 56 5 mg/kg CAT-354 on Day 0, 28, and 56 10 mg/kg CAT-354 on Day 0, 28, and 56
• Placebo
Placebo to match all doses of CAT-354 on Day 0, 28, and 56.

Locations

Country	Name	City	State
Australia	Eastern Clinical Research Unit	Box Hill	Victoria
Australia	Monash Medical Centre, Dept Respiratory Medicine.	Clayton	Victoria
Australia	St. Vincents Hospital, Thoracic Medicine Unit	Darlinghurst	New South Wales
Australia	Dep of Respiratory & Sleep Medicine, Western Hospital	Footscray	Victoria
Australia	Lung Institute WA, Sir Charles Gardner Hospital	Nedlands	Western Australia
Australia	WA Lung Research, Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Respiratory & Sleep Medicine, Royal Melbourne Hospital	Parkville	Victoria
Australia	Respiratory Medicine Department, Mater Adult Hospital,	South Brisbane	Queensland
Australia	Princess Alexandria Hospital, Dept of Respiratory Medicine	Woolloongabba	Queensland
Germany	Evangelische Lungenklinik Berlin - Kardiologie/Pneumologie - 1.OG, Haus 23	Berlin
Germany	Med. Klinik m. S. Infektiologie und Pneumologie, Charite - Universitätsmedizin Berlin	Berlin
Germany	Lungen und Bronchialheikunde	Bonn
Germany	Praxis für Lungen-und Bronchialheilkunde, Allergologie und Umweltmedizin	Bonn
Germany	Rheinische Friedrich-Wilhelms-Universität, Medizinische Klinik und Poliklinik II, Innere Medizin	Bonn
Germany	Internistisches Facharztzentrum Stresemannallee	Frankfurt
Germany	Universitätsklinikum Magdeburg Fachbereich Pneumologie	Magdeburg
Germany	Universitätsklinikum Mainz, Klinische Forschung Pneumologie, III. med. Klinik	Mainz
Germany	Universitätsklinikum Münster Klinik und Poliklinik für Dermatologie	Munster
Germany	Universität Rostock, Medizinische Fakultät Klinik und Poliklinik für Innere Medizin	Rostock
Germany	Johanniter-Krankenhaus im Fläming gGmbH, Pneumologie	Treuenbrietzen
Netherlands	Academisch Medisch Centrum	Amsterdam
Poland	ISPL Centrum Medyczne	Bialystok
Poland	Prywatny Gabinet Internistyczno-Alergologiczny	Bialystok
Poland	Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej Akademii Medycznej, Klinika Pneumologii	Katowice
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Atopia	Kraków
Poland	Uniwersytecki Szpital Kliniczny nr 1 Im. Norberta Barlickiego w Lodzi	Lódz
Poland	Szpital ZOZ Lubin Oddzial Alergologiczny i Chorob Wewnetrznych	Lubin
Poland	Alergopneuma Przychodnia Alergologiczno-Pulmonologiczna Marek Michnar i wsp.	Lublin
Poland	Wojewodzki Szpital Specjalistyczny, Poradnia Alergologiczna	Lublin
Poland	Instytut Gruzlicy i Chorob Pluc	Warszawa
Poland	Wojewódzki Szpital Specjalistyczny w Zgierzu	Zgierz
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Gartnavel General Hospital	Glasgow
United Kingdom	University Hospitals of Leicester NHS Trust, Glenfield Hospital	Leicester
United Kingdom	Royal Brompton Hospital	London
United Kingdom	University Hospital of South Manchester NHS Foundation Trust	Manchester
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Royal Gwent Hospital	Newport
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United Kingdom	Lister Hospital	Stevenage, Hertfordshire

Sponsors (3)

Lead Sponsor	Collaborator
MedImmune LLC	Cambridge Antibody Technology, PRA Health Sciences

Countries where clinical trial is conducted

Australia,  Germany,  Netherlands,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary endpoint for this study will be the doubling concentration of methacholine at Visit 5 compared with the pre dose value at Visit 2.		TBD	No