Single Dose of pGM169/GL67A in CF Patients

NCT00789867 | Completed Phase 1 Results DMC

• 1 other identifier: cro851
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

Single dose; Pilot; Safety; Gene expression; Tolerability; CFTR gene; Cystic fibrosis; Non-viral

Outcome Measures

Primary Outcomes (6)

• Body Maximum Temperature

  6-8h

• Blood Leukocytes

  Blood leukocytes measure

  8h

• Blood Neutrophils

  Blood neutrophils measures

  8h

• FEV1 Relative % Drop

  FEV1 relative % drop measure

  8h

• FVC Relative % Drop

  FVC relative % drop measure

  6h

• Lung Clearance Index - LCI

  Lung clearance index measure is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout technique.

  8h

Study Arms (3)

20ml pGM169/GL67A

EXPERIMENTAL

Received a nebulized dose 20ml via an breath-actuated nebulizer

Drug: pGM169/GL67A

10ml pGM169/GL67A

EXPERIMENTAL

Received a nebulized dose 10ml via an breath-actuated nebulizer

Drug: pGM169/GL67A

5ml pGM169/GL67A

EXPERIMENTAL

Received a nebulized dose 5ml via an breath-actuated nebulizer

Drug: pGM169/GL67A

Interventions

pGM169/GL67A DRUG

Received a nebulized dose via an breath-actuated nebulizer

Also known as: 5ml pGM169/GL67A, 10ml pGM169/GL67A and 20ml pGM169/GL67A

10ml pGM169/GL67A; 20ml pGM169/GL67A; 5ml pGM169/GL67A

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Imperial College London: lead
• Royal Brompton & Harefield NHS Foundation Trust: collaborator
• University of Oxford: collaborator
• University of Edinburgh: collaborator
• Cystic Fibrosis Trust: collaborator
• University of Pennsylvania: collaborator

Study Sites (1)

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Related Publications (2)

• Alton EW, Stern M, Farley R, Jaffe A, Chadwick SL, Phillips J, Davies J, Smith SN, Browning J, Davies MG, Hodson ME, Durham SR, Li D, Jeffery PK, Scallan M, Balfour R, Eastman SJ, Cheng SH, Smith AE, Meeker D, Geddes DM. Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet. 1999 Mar 20;353(9157):947-54. doi: 10.1016/s0140-6736(98)06532-5.

  PMID: 10459902 BACKGROUND

• Alton EW, Boyd AC, Porteous DJ, Davies G, Davies JC, Griesenbach U, Higgins TE, Gill DR, Hyde SC, Innes JA; UK Cystic Fibrosis Gene Therapy Consortium *. A Phase I/IIa Safety and Efficacy Study of Nebulized Liposome-mediated Gene Therapy for Cystic Fibrosis Supports a Multidose Trial. Am J Respir Crit Care Med. 2015 Dec 1;192(11):1389-92. doi: 10.1164/rccm.201506-1193LE. No abstract available.

  PMID: 26623687 RESULT

Related Links

• UK CF Gene Therapy Consortium website

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Samia Soussi
• Organization: Imperial College

s.soussi@imperial.ac.uk

0207 594 7980

Study Officials

• Eric Alton

  Imperial College London

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2008
• First Posted: November 13, 2008
• Study Start: November 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: December 1, 2010
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)