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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by University Hospital Southampton NHS Foundation Trust..
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier:
NCT01386151
First received: June 24, 2011
Last updated: June 29, 2011
Last verified: June 2010
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 21, 2014