A study to assess the safety and the effects of using a growth factor, keratinocyte growth factor (KGF), in patients with moderate asthma

ISRCTN	ISRCTN02767559
DOI	https://doi.org/10.1186/ISRCTN02767559
Secondary identifying numbers	BRU 3.1, Sponsor no. RHM MED 0879

Submission date: 16/06/2009
Registration date: 07/10/2009
Last edited: 24/05/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Peter Howarth
Scientific

IIR (RCMB) MP810
Level F, South Block
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Email	P.H.Howarth@soton.ac.uk

Study information

Study design	Randomised double blind placebo controlled parallel group trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Safety and efficacy of parenteral keratinocyte growth factor (KGF) in moderate asthma subjects: a double-blind placebo-controlled randomised parallel group trial
Study objectives	That restoration of the bronchial epithelial barrier in asthma by treatment with KGF will reduce the responsiveness of the lungs to bronchoconstrictor agents, reduce airway inflammation and improve clinical disease expression.
Ethics approval(s)	Pending as of 17/06/2009 from the Southampton and South West Hampshire Local Research Ethics Committee (LREC)
Health condition(s) or problem(s) studied	Asthma
Intervention	The study population will be screened including medical history, examination, spirometry, diary card monitoring, exhaled nitric oxide measurement, skinprick testing, mannitol and metacholine provocation tests and baseline bronchoscopy. The intervention group will receive intravenous keratinocyte growth factor (KGF) in a 'collapsed dose' regime, at a dose of 180 µg/kg, given as an infusion on days 0 and day 11 of the trial. The control group will receive saline infusions. In between the doses and following the second doses the subjects will have further provocation tests and a further bronchoscopy. Subjects will be followed up for 36 days following the initial dose of the study drug/placebo.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Keratinocyte growth factor
Primary outcome measure	Change in provocative concentration in mannitol causing a 20% fall in FEV1 (PC20), measured in screening and on days 3, 14, 18 and 36
Secondary outcome measures	1. Asthma symptoms, assessed continuously during the trial 2. Short acting B-2-agonist usage, assessed continuously during the trial 3. Lung function (home peak expiratory flow rate [PEFR] recording and clinic FEV1 and forced vital capacity [FVC]) 4. Change in PC20 methacholine, assessed in screening and on day 17 and 35 5. Change in exhaled NO (eNO), assessed in screening and on days 3, 14, 18 and 36 6. Expression of ZO-1 and occludin in the bronchial epithelium 7. Bronchial biopsy epithelial integrity 8. Mucosal cellular inflammation (eosinophils, mast cells, neutrophils T-cells), assessed from bronchocopy in screening and on day 21 9. Epithelial activation markers (interleukin-8 [IL-8], regulated upon activation, normal T cell expressed and secreted [RANTES], macrophage inflammatory protein-1alpha [MIP-1a], macrophage chemotactic protein-1 [MCP-1], transforming growth factor alpha [TGF-a], epidermal growth factor receptor [EGFR]), assessed from bronchocopy in screening and on day 21 10. Safety readouts (clinical adverse event reporting), assessed continuously 11. Safety-related histochemistry readouts (epithelial Ki 61), assessed continuously
Overall study start date	01/08/2009
Completion date	01/11/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	50 Years
Sex	Both
Target number of participants	20
Key inclusion criteria	1. Aged 18 - 50 years, either gender 2. Confirmed diagnosis of asthma for greater than 1 year as defined by British Thoracic Society (BTS) guidelines, requiring treatment with high dose inhaled corticosteroids in combination with long acting beta-2-agonists, with persisting symptoms requiring use of short-acting beta agonist therapy greater than 3 x/week 3. Lifelong non-smoker 4. Forced expiratory volume in one second (FEV1) greater than 40% 5. Subject must understand the procedures of the study and agree to participation in the study by providing written informed consent 6. Subject considered fit enough to undergo lung function testing including provocation tests, and bronchoscopy 7. Subject must not be participating in another clinical trial or have done so within the last 12 weeks
Key exclusion criteria	1. Pregnancy (where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin [hCG] laboratory test greater than 5 mIU/ml), an intention to become pregnant or breast-feeding (lactating) 2. Subjects with active lung disease other than asthma 3. Significant medical (cardiopulmonary, neurological, renal, endocrine, gastrointestinal, psychiatric, hepatic or haematological) co-morbidity which in the view of the investigator could impact on the interpretation of results or participation in the trial, or which is uncontrolled with standard treatment 4. Current participation in another clinical trial or previous participation within the last 12 weeks 5. Alcohol or active drug abuse 6. Ongoing allergen desensitisation therapy 7. Regular use of sedatives, hypnotics, tranquilisers 8. Cancer or previous history of cancer 9. Inability to understand directions for dosing and study assessment 10. Inability to be contacted in case of emergency
Date of first enrolment	01/08/2009
Date of final enrolment	01/11/2009

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

IIR (RCMB) MP810

Southampton
SO16 6YD
United Kingdom

Sponsor information

Southampton University Hospitals NHS Trust (UK)
Hospital/treatment centre

Research and Development
Duthie Building (Trust) MP138
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
England
United Kingdom

Phone	+44 (0)2380 794 149
Email	angela.jackson@suht.swest.nhs.uk
Website	http://www.suht.nhs.uk/home.aspx
"ROR"	https://ror.org/0485axj58

Funders

Funder type

Hospital/treatment centre

Southampton General Hospital (UK) - Internal funding by Biomedical Research Unit

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

24/05/2016: No publications found, verifying study status with principal investigator