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Trial record 1 of 1 for:    NCT00789867
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Single Dose of pGM169/GL67A in CF Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00789867
Recruitment Status : Completed
First Posted : November 13, 2008
Results First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Sponsor:
Collaborators:
Royal Brompton & Harefield NHS Foundation Trust
University of Oxford
University of Edinburgh
Cystic Fibrosis Trust
University of Pennsylvania
Information provided by (Responsible Party):
Imperial College London

Brief Summary:
The study objectives are to assess safety, tolerability and gene expression after a single dose of non-viral CFTR gene therapy (pGM169/GL67A) administered to the nose and lungs of patients with cystic fibrosis.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: pGM169/GL67A Phase 1 Phase 2

Detailed Description:

The trial is designed as single administration to nose and lung. Initially, in Part A, 3 patients will be dosed individually one week apart with 10 ml (26.5mg pDNA) via nebuliser and a nasal dose equivalent to 10% of this (based on relative surface area calculations: conducting airways approximate 540 cm2; nasal epithelium from both nostrils approximately 40 cm2). Based on our previous study, we do not expect any side effects of the nasal dose, but we are taking this opportunity, as this group will not be undergoing bronchoscopic efficacy measures, to assess gene transfer to the nasal epithelium. A further group of 3 patients will then be treated in exactly the same way with 20 ml nebulised and a 2 ml nasal dose.

Subsequently, patients will receive doses of 2 ml (nasal) and 20 ml (nebulised). These patients will undergo more intensive monitoring for gene expression both before and after administration.

In Part B of the protocol, we will test combinations of delivery conditions and dose in an attempt to identify the maximal tolerated dose. We may also use Ibuprofen or Prednisolone in standard clinical doses around the dosing period to reduce the inflammatory response. Delivery conditions include: standard nebulisation (each 5 ml over 25 minutes as in Part A), slow (each 5 ml over 75-150 minutes) and divided (standard rate delivery with a period of up to 6 hours between aliquots). With these conditions we will test the following doses until a tolerable dose is reached: 20 ml (no standard delivery as sufficient data already available from Part A); 10 ml; 5 ml; 2.5 ml. Each dosing strategy will initially be performed in a cohort of 3 patients although numbers may need to be increased to 6 if data are inconclusive. Once a satisfactory Single dose of pGM169/GL67A in CF patients; cro851 Version 10; 16.08.2010 10 dose and nebulisation strategy has been identified, the numbers receiving this will be increased to 6. The maximum number of patients recruited to this arm of the study will be 30. Part B will also allow either these subjects or others to receive a 2 ml nasal dose with both pre and post-measurements of nasal PD.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Safety and Gene Expression With a Single Dose of pGM169/GL67A Administered to the Nose and Lung of Individuals With Cystic Fibrosis
Actual Study Start Date : November 2008
Actual Primary Completion Date : August 2009
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: 20ml pGM169/GL67A
Received a nebulized dose 20ml via an breath-actuated nebulizer
Drug: pGM169/GL67A
Received a nebulized dose via an breath-actuated nebulizer
Other Name: 5ml pGM169/GL67A, 10ml pGM169/GL67A and 20ml pGM169/GL67A

Experimental: 10ml pGM169/GL67A
Received a nebulized dose 10ml via an breath-actuated nebulizer
Drug: pGM169/GL67A
Received a nebulized dose via an breath-actuated nebulizer
Other Name: 5ml pGM169/GL67A, 10ml pGM169/GL67A and 20ml pGM169/GL67A

Experimental: 5ml pGM169/GL67A
Received a nebulized dose 5ml via an breath-actuated nebulizer
Drug: pGM169/GL67A
Received a nebulized dose via an breath-actuated nebulizer
Other Name: 5ml pGM169/GL67A, 10ml pGM169/GL67A and 20ml pGM169/GL67A




Primary Outcome Measures :
  1. Body Maximum Temperature [ Time Frame: 6-8h ]
  2. Blood Leukocytes [ Time Frame: 8h ]
    Blood leukocytes measure

  3. Blood Neutrophils [ Time Frame: 8h ]
    Blood neutrophils measures

  4. FEV1 Relative % Drop [ Time Frame: 8h ]
    FEV1 relative % drop measure

  5. FVC Relative % Drop [ Time Frame: 6h ]
    FVC relative % drop measure

  6. Lung Clearance Index - LCI [ Time Frame: 8h ]
    Lung clearance index measure is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout technique.



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cystic fibrosis confirmed by sweat testing or genetic analysis
  • Males and females aged 16 years and above
  • Forced expiratory volume in the 1st second (FEV1) > 60% predicted values
  • Clinical stability at entry
  • Prepared to take effective contraceptive precautions for the duration of their participation in the study and for 3 months thereafter
  • If taking regular rhDNase (pulmozyme) is willing, and considered able by independent medical carers, to withhold treatment for 24 hours before and 24 hours after the gene therapy dose
  • Written informed consent obtained
  • Permission to inform GP of participation in study

Exclusion Criteria:

  • Infection with Burkholderia cepacia complex organisms or MRSA
  • Significant nasal pathology including polyps, clinically-significant rhinosinusitis, or recurrent severe epistaxis (nose bleeds)
  • Acute upper respiratory tract infection within the last 2 weeks
  • Previous spontaneous pneumothorax without pleurodesis
  • Recurrent severe haemoptysis
  • Current smoker
  • Significant comorbidity including:

    1. Moderate/severe CF liver disease
    2. Significant renal impairment
    3. Significant coagulopathy
  • Receiving 2nd line immunosuppressant drugs such as methotrexate, cyclosporine, intravenous immunoglobulin preparations
  • Pregnant or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00789867


Locations
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United Kingdom
Royal Brompton Hospital
London, United Kingdom, SW3 6NP
Sponsors and Collaborators
Imperial College London
Royal Brompton & Harefield NHS Foundation Trust
University of Oxford
University of Edinburgh
Cystic Fibrosis Trust
University of Pennsylvania
Investigators
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Study Director: Eric Alton Imperial College London
Principal Investigator: Jane C Davies Imperial College London
Principal Investigator: Uta Griesenbach Imperial College London
Principal Investigator: Steve Hyde University of Oxford
Principal Investigator: Deborah Gill University of Oxford
Principal Investigator: David Porteous Edinburgh University
Principal Investigator: Chris Boyd Edinburgh University
Principal Investigator: Alastair Innes Edinburgh University
Additional Information:
Publications of Results:
Other Publications:
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00789867    
Other Study ID Numbers: cro851
First Posted: November 13, 2008    Key Record Dates
Results First Posted: January 18, 2020
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
Single dose
Pilot
Safety
Gene expression
Tolerability
CFTR gene
Cystic fibrosis
Non-viral
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases