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

October 12, 2016 updated by: University Hospital Southampton NHS Foundation Trust

Safety and Efficacy of Parenteral KGF in Moderate Asthmatic Subjects

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD
        • Biomedical Research Unit (Respiratory)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
A standard bronchoprovocation test, metacholine challenge, will be used to assess airway hyperreactivity (by measuring the concentration needed to drop FEV1 by 20%, PC20)
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
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).
Symptoms will be assessed using standardised questionnaires, Asthma control questionnaire (ACQ) and Asthma Quality of Life questionnaire (AQLQ)
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
Time Frame: Throughout study
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
Throughout study
Adverse event reporting
Time Frame: Throughout study
Adverse events will be recorded if they occur
Throughout study
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)
Bronchial biopsies, brush specimens and lavage fluid before and after intervention will be analysed to determine markers of activation, inflammation and epithelial integrity
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)
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)
Bronchial biopsy specimens will be analysed for markers of proliferation e.g. Ki67 before and after treatment
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)
Exhaled nitric Oxide
Time Frame: This is measured on the same days as PD15 mannitol, with an additional baseline measurement at the screening visit
Exhaled nitric oxide, as a surrogate marker of eosinophilic inflammation, will be measured before/during and after intervention
This is measured on the same days as PD15 mannitol, with an additional baseline measurement at the screening visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Southampton NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Peter H Howarth, BSc, MBBS, Reader in Medicine and Honorary Consultant Physician, Southampton General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 24, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 30, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 13, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 12, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RHM MED 0879

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Bronchial Asthma

Clinical Trials on Keratinocyte Growth factor

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings