by Dr Martin Boeree
Representatives of 11 African clinical trial sites and 3 European Universities, representatives of EDCTP, and pharmaceutical industry met for a kick-off of this new Consortium. Intensive and constructive discussions were held on the science, the governance, the timelines and the capacity development aspects of the sites. They were very nicely hosted by the KCRI, the Kilimanjaro Clinical Research Institute, in Moshi, through it Director and site PI, Dr. Gibson Kibiki.
Current treatment regimens for tuberculosis (TB) remain unacceptably long, which may result in poor compliance, the risk of relapse, and the development of drug resistant strains of TB. Improving treatment outcomes requires the development of new drugs and drug regimens to shorten and simplify TB treatment.
On 31 May 2007, in Dublin, Ireland, the European and Developing Countries Clinical Trials Partnership (EDCTP) held a stakeholder meeting to address the state of TB drugs. With the goal of shortening and simplifying treatment of drug-sensitive TB, EDCTP recommended a brokered approach to conducting clinical trials for new drugs. An important outcome of this meeting was a Call for Expression of Interest issued on 1 August 2007.
Subsequently, EDCTP invited five applicants, each representing a consortium of institutions, to participate in a brokering meeting held in The Hague on 4 December 2007. One outcome of this meeting was the formation of a consortium of consortia to develop a proposal to EDCTP focused on (1) collaboration across the consortia in the conduct of regulatory-standard Phase IIa, IIb, and Phase III clinical trials for 4 TB drugs, and (2) collaboration across the consortia to develop increased capacity in sub-Saharan Africa for the conduct of ICH-GCP and GCLP compliant clinical trials for TB drugs.
This TB consortium of consortia, known as the Pan African Consortium for Evaluation of Antituberculosis Antibiotics (PanACEA), will provide synergies and efficiencies in the conduct of the trials and capacity development. The PanACEA participating institutions have 20 years of experience in developing Research and Development and Capacity Development programs in Africa. All three of the clinical trials’ Principal Investigators (PIs) are committed to a joint Clinical Trials and Capacity Development Program as presented in a recently approved proposal to the EDCTP.
The overall objectives for the PanACEA program focus on the effective, efficient conduct of the proposed clinical trials and on establishing an enduring framework to benefit future trials of TB drugs. Only with a consortium of clinical trials and trial sites can these objectives be accomplished at the comprehensive scope required to transform TB drug development and improve TB treatment regimens that have not changed significantly over the past 35 years.
The proposed objectives for PanACEA include the following:
- Shorten and Simplify TB Therapy: To develop new regimens for shortening and simplifying TB treatment from the current 6 months to 4 months. This objective will be accomplished by conducting regulatory-quality EBA, Phase II and III clinical trials initially for three drugs. A fourth drug (rifapentine) will enter clinical trials later.
- Establish TB Clinical Trial Capacity: To establish the required clinical trial capacity as new TB drugs move through the development pipeline. This objective will be accomplished by the development of registration-quality TB clinical trial capacity at 12 sites in sub-Saharan Africa.
- Establish Tools and Framework for TB Trials: To develop an enduring framework for the efficient conduct of the proposed and future clinical trials for TB drugs. This objective will be accomplished by establishing an African-led consortium board that will develop experience in generating and disseminating best practices in the form of standard operating procedures (SOPs), manuals, training curricula, and other tools and processes for TB clinical trials.
The PanACEA consists of three consortia
- REMox: the Rapid Evaluation of Moxifloxacin in Tuberculosis, sponsored by the University College London. Chief Investigator: Stephen Gillespie
- HIGHRIF: the Rapid Evaluation of High-Dose Rifampicin and Other Rifamycines, sponsored by the Radboud University Nijmegen Medical Centre. Chief Investigator: Martin Boeree
- SQ109: Evaluation of a Novel TB drug (SQ109) to Shorten and Simplify Tuberculosis Treatment, sponsored by the Ludwig University of Munich. Chief Investigator: Michael Hoelscher
And perform their drug development programme in 12 African sites:
- Aurum Institute for Health Research
- Makarere University
- Mbeya Medical Research Progam
- Kilimanjaro Christian Medical Center – Moshi
- University of Stellenbosch
- University of Cape Town
- University of Zambia
- University of the Witwaterstand
- Bagamoyo IHRDC and Swiss Trop. Inst.
- Albert Schweitzer Hospital – Lambarene
- South African MRC (Durban)
- Kenya Medical Research Institute
PanACEA is funded for a period of 5 years. In this period the deliverables will be to have tried moxifloxacine beyond phase III, high dose rifampicine and SQ 109 beyond phase II, have developed the trial sites to be able to perform GCP/GCLP regulatory standard clinical trials in TB drug development and have secured additional funding to build a sustainable programme.