Present: Professor Norman Nevin (Chair), Mrs Debbie Beirne, Professor Martin Gore, Professor Terry Hamblin, Professor Jim Neil, Rev Dr Lee Rayfield, Dr Adrian Lepper, Dr Michael Waterhouse, Dr Richard Ashcroft, Professor Andrew Lever, Dr Caroline Benjamin, Professor David Harrison, Mr Michael Harrison, Mrs Fiona Sandford, Professor Alex Markham, and Dr Peter Harris.

Observer: Dr Mike Mackett (HSE).

Secretariat: Dr Jayne Spink, Dr Monika Preuss, and Mr Daniel Gooch.

Item 1: Introduction

The Chair welcomed the Committee to its first meeting of 2004. The Chair mentioned the press release announcing the halt of the stable angina study GTAC 051. This study was one of the biggest UK gene therapy trials.


Item 2: Minutes of the 45th meeting of GTAC

The minutes were agreed, subject to a few minor amendments, as an accurate and true record of the meeting.

Item 3: Matters Arising

Correspondence. The letters sent out concerning correspondence arising from the last meeting gave rise to a small amount of discussion on the writing of guidance notes, the value of post mortems, and the correspondence regarding the angina trial which was not yet fully resolved.

Update on White Paper commitments. The Secretariat gave a brief update on progress on the Government's White Paper's gene therapy commitments. The Commissioning Panel had met, and an announcement on funding was expected within a few weeks. No decision on the £4 million vector production commitment has yet been made.

Update on the clinical trials regulations. The Secretariat had obtained agreement that GTAC will be named in the Clinical Trials Regulations as the UK body to deal with clinical gene therapy research. A specialist appeals mechanism will be provided. The proposed appeals mechanism was provided as a tabled paper, and Mr Michael Harrison was thanked for his input.

Item 4 - GTAC 089: A Phase I/II Trial of a DNA vaccine given to patients with prostate carcinomas with or without electroporation

A number of members declared potential interests. This was a new protocol for the treatment of prostate cancer at Southampton Hospital. It is an immunotherapy study which aims to stimulate the immune system to act against prostate cancer in patients with incurable disease. The study uses a DNA vaccine that encodes an epitope derived from prostate specific membrane antigen. This is linked to an immune alert sequence (fragment C of tetanus toxin) to further stimulate an appropriate immune response. The applicants wished to use a process called electroporation as a means of improving the efficacy of DNA delivery to muscle cells. Electroporation is the application of a short electric current at the same time as injecting the DNA.

The applicants presented this proposal to the Committee, and answered questions. Following discussion, GTAC decided to conditionally approve the study subject to some amendments.

Tabled paper: GTAC 55 prostate cancer trial: amendment of the liver toxicity criteria

Dr Harris declared a potential interest as he is a consultant to the trial sponsor. The protocol utilises Gene Directed Enzyme Prodrug Therapy for prostate cancer. Tumours are injected with the study product (CTL102, adenovirus) which contains the nitroreductase (NTR) gene. Following delivery of CLT102, patients are dosed with the pro-drug (CB1954). Those tumour cells that produce NTR convert the pro-drug to a toxic form, leading to the death of the cancerous cells.

Recent results had shown that the parameter to determine liver dose-limiting toxicity (DLT) might not be appropriate. The committee discussed several options for review of the trigger for DLT and agreed on the most appropriate parameter. The Secretariat was instructed to write to the proposers giving GTAC approval to the agreed revision.

Item 5 - The draft GTAC Tenth Annual Report

The Committee went through the draft of the Tenth Annual Report, and a number of comments were made which the Secretariat would implement in the preparation of the final version for submission to Ministers for approval.

Item 6 - Chairman's Actions

There were no comments on the five Chairman's actions taken since the last meeting.

Item 7 - SAE Update

There were no substantial comments on the seven SAEs received by the Secretariat since the last meeting.

Item 8: Any other Business

Antisense workshop. As a result of the discussion of the antisense trial at the last meeting, GTAC thought it was appropriate to organise a workshop on antisense trials to develop a strategy for processing applications in future. The Committee provisionally agreed on Wednesday 12 May 2004 as a suitable date for the workshop. A number of suggestions were made as to possible attendees, and it was thought that a primer session before the workshop could be useful.

The public meeting 2004. The Secretariat suggested holding the GTAC open day in Cambridge on the day before or after the 21 July committee meeting. The Secretariat suggested holding both meetings in Cambridge. Possible topics for the open meeting were discussed.

Training of Members. The Secretariat has received many valuable and positive comment / suggestions. The Chairman suggested that the Committee could fit in half-hour training elements to future agendas, at the beginning, and/or end, of the meeting. These could cover topics such as "storage of samples", "implications of clinical trial regulations", and "informed consent". The format could be discussion rather than presentation. An opportunity to visit a clinical gene therapy site could also be useful.

GTAC/CSM recommendation (discussed by RAC) and clinical trial compensation guidelines. Material regarding the above was included for information.

Press cuttings

Provided was some background reading on the marketing of gene therapy drugs, viral vectors, and a research paper on the strategy of Gene Directed Enzyme Prodrug Therapy (also used in the GTAC 055 study). There was also a copy of the Government statement on neuroscience following the decision by Cambridge University not to go ahead with its planned primate research centre. Also reproduced was an article in Nature on the continued resistance in the EU research community to the Clinical Trials Directive.

The next committee meeting is Wednesday, 21 April 2005

GTAC Secretariat
July 2004

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