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

NCT01386151 | Completed Phase 2

• 1 other identifier: RHM MED 0879
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Bronchial Asthma

Keywords

Moderate asthmatic, uncontrolled

Outcome Measures

Primary Outcomes (1)

• Change in PD15 Mannitol

  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)

  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)

Secondary Outcomes (7)

• Change in PC20 Metacholine

  Baseline (6 days prior to drug) and short/intermediate term post drug period (7 and 25 days after second drug administration)

• Change in asthma symptoms

  ACQ is measured weekly during study. AQLQ is measured at baseline screening visit, and on day 35 (35 days post first administration of drug).

• Short acting beta-agonist use/PEFR variability

  Throughout study

• Adverse event reporting

  Throughout study

• Epithelial integrity/activation

  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)

Study Arms (2)

Study drug

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Saline will be used as a placebo comparator

Drug: Saline placebo

Interventions

Keratinocyte Growth factor DRUG

KGF will be administered intravenously in a 'collapsed dose' regime of 180ug/kg on day 0 and day 11

Also known as: Palifermin, rhKGF, Kepivance

Study drug

Saline placebo DRUG

Normal (0.9%) saline will be used as a placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead

Study Sites (1)

Biomedical Research Unit (Respiratory)

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

Fibroblast Growth Factor 7

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Peter H Howarth, BSc, MBBS

  Reader in Medicine and Honorary Consultant Physician, Southampton General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2011
• First Posted: June 30, 2011
• Study Start: August 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: October 13, 2016

Record last verified: 2016-10

Locations

GB (1)