A Study to Assess Safety and Efficacy of a Novel Treatment, Keratinocyte Growth Factor (KGF), in Asthmatic Patients - Full Text View

Purpose

This study will look at the permeability, or 'leakiness' of the airway epithelium (the inner lining of the lung) in asthmatic patients. Increased leakiness of this lining has been shown in asthmatic patients by other studies, not only in the lung but also possibly in the gut, perhaps reflecting a widespread defect. This leakiness may underline the interaction between the environment and a person's genetic make up, and may contribute to why some people get asthma, and how severe it is. Increased leakiness may allow increased exposure to inhaled allergic substances, helping to perpetuate the inflammation in the lungs that is a hallmark of asthma.

Specifically, this study will attempt to modify and reduce this permeability through the use of a substance called 'keratinocyte growth factor', or 'kgf'. KGF is a naturally occuring human protein, which is involved in stimulating the growth of cells lining the layers of the skin and gut, helping to repair damage and maintain their structure. It has been manufactured in a laboratory as the commercial compound 'Palifermin', which has already been used in humans to reduce damage to the lining of the mouth after chemotherapy. The study will see if Palifermin can similarly improve the lining of the lung in asthma patients and improve their symptoms. To date no treatments have been used in this area in asthma, and if successful the study will open up a whole new area of therapy

Condition	Intervention	Phase
Bronchial Asthma	Drug: Keratinocyte Growth factor Drug: Saline placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Safety and Efficacy of Parenteral KGF in Moderate Asthmatic Subjects

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Palifermin

U.S. FDA Resources

Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Primary Outcome Measures:

Change in PD15 Mannitol [ Time Frame: Baseline (7 days prior to drug), during drug administration period (3 days after first dose of drug), and short/intermediate term post drug period (3, 6 and 24 days after second drug administration) ] [ Designated as safety issue: No ]
A standard bronchoprovocation test, the mannitol test, will be used to assess airway hyperreactivity (measured as the dose required to drop FEV1 (forced expiratory volume in 1 second) by 15%, PD15)

Secondary Outcome Measures:

Change in PC20 Metacholine [ Time Frame: Baseline (6 days prior to drug) and short/intermediate term post drug period (7 and 25 days after second drug administration) ] [ Designated as safety issue: No ]
A standard bronchoprovocation test, metacholine challenge, will be used to assess airway hyperreactivity (by measuring the concentration needed to drop FEV1 by 20%, PC20)
Change in asthma symptoms [ Time Frame: ACQ is measured weekly during study. AQLQ is measured at baseline screening visit, and on day 35 (35 days post first administration of drug). ] [ Designated as safety issue: No ]
Symptoms will be assessed using standardised questionnaires, Asthma control questionnaire (ACQ) and Asthma Quality of Life questionnaire (AQLQ)
Short acting beta-agonist use/PEFR variability [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
A diary card will be used throughout the study for participants to record beta-agonist use and morning/evening peak expiratory flow rates (PEFR), from the latter PEFR variability will be calculated
Adverse event reporting [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Adverse events will be recorded if they occur
Epithelial integrity/activation [ Time Frame: Specimens are taken at 2 bronchoscopies, the first before the drug (4 days prior to the first drug administration) and the second after the drug (21 days after the first drug administration) ] [ Designated as safety issue: No ]
Bronchial biopsies, brush specimens and lavage fluid before and after intervention will be analysed to determine markers of activation, inflammation and epithelial integrity
Epithelial proliferation [ Time Frame: Specimens are taken at 2 bronchoscopies, the first before the drug (4 days prior to the first drug administration) and the second after the drug (21 days after the first drug administration) ] [ Designated as safety issue: Yes ]
Bronchial biopsy specimens will be analysed for markers of proliferation e.g. Ki67 before and after treatment
Exhaled nitric Oxide [ Time Frame: This is measured on the same days as PD15 mannitol, with an additional baseline measurement at the screening visit ] [ Designated as safety issue: No ]
Exhaled nitric oxide, as a surrogate marker of eosinophilic inflammation, will be measured before/during and after intervention

Estimated Enrollment:	20
Study Start Date:	August 2009
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Study drug Keratinocyte growth factor (KGF) will be administered intravenously in a 'collapsed dose' regime of 180ug/kg on day 0 and day 11.	Drug: Keratinocyte Growth factor KGF will be administered intravenously in a 'collapsed dose' regime of 180ug/kg on day 0 and day 11 Other Name: Palifermin, rhKGF, Kepivance
Placebo Comparator: Placebo Saline will be used as a placebo comparator	Drug: Saline placebo Normal (0.9%) saline will be used as a placebo.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18 - 60 years, either gender
Confirmed diagnosis of asthma for > 1 year as defined by BTS guidelines, requiring treatment with high dose inhaled corticosteroids +/- long acting β2 agonists, with persisting symptoms requiring use of short-acting beta agonist therapy >3x/week.
Never-smoker or ex-smoker, having stopped >1 year ago, with <10 pack year history.
Subject must understand the procedures of the study and agree to participation in the study by providing written informed consent
Subject considered fit enough to undergo lung function testing including provocation tests, and bronchoscopy.
Subject must not be participating in another clinical trial or have done so within the last 12 weeks.

Exclusion Criteria:

Patients requiring regular maintenance oral steroids for their asthma, or those who are adhering to symbicort SMART single inhaler regime.
Pregnancy (where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test >5mIU/ml), an intention to become pregnant or breast-feeding (lactating).
Subjects with active lung disease other than asthma
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.
Current participation in another clinical trial or previous participation within the last 12 weeks.
Alcohol or active drug abuse.
Ongoing allergen desensitisation therapy
Regular use of sedatives, hypnotics, tranquilisers
Cancer or previous history of cancer
Inability to understand directions for dosing and study assessment.
Inability to be contacted in case of emergency.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01386151

Contacts

Contact: Peter H Howarth, BSc, MBBS, MRCP, FRCP	02380 796990	P.H.Howarth@soton.ac.uk
Contact: Patrick W Dennison, BA(Phys Sci), BMBCh, MRCP	02380777222 ext 3308	pd1d08@soton.ac.uk

Locations

United Kingdom
Biomedical Research Unit (Respiratory)	Recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Principal Investigator: Peter H Howarth, BSc, MBBS
Sub-Investigator: Patrick W Dennison, BA(Phys Sci), BMBCh

Sponsors and Collaborators

University Hospital Southampton NHS Foundation Trust.

Investigators

Principal Investigator:

Peter H Howarth, BSc, MBBS

Reader in Medicine and Honorary Consultant Physician, Southampton General Hospital

More Information

No publications provided

Responsible Party:	Dr Peter Howarth (Principal Investigator), Biomedical Research Unit (Respiratory), Southampton General Hospital
ClinicalTrials.gov Identifier:	NCT01386151 History of Changes
Other Study ID Numbers:	RHM MED 0879
Study First Received:	June 24, 2011
Last Updated:	June 29, 2011
Health Authority:	United Kingdom: Medicines and Health Regulatory Authority (MHRA)

Keywords provided by University Hospital Southampton NHS Foundation Trust.:

Moderate asthmatic, uncontrolled

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate

Hypersensitivity
Immune System Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013