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WORK PACKAGES

Work Package 1: Project Management

Project Management

OBJECTIVES
To perform core administrative, financial, reporting, ethical and regulatory functions, and to facilitate other work packages.

DESCRIPTION OF WORK TO BE CONDUCTED
As lead, Aurum will arrange contracts with participants and contractors, arrange trial insurance, establish billing and other accounting procedures, arrange meetings with FDA and EMA, perform local ethical and regulatory submissions and updates, assist other sites in similar submissions, arrange annual meetings and training activities, arrange TSC and DSMB meetings, and prepare recruitment and other periodic reports. Other participants will establish grant and financial management procedures, execute them, and perform local ethical and regulatory submissions as a part of this work package.

RESPONSIBLE ORGANISATION

The Aurum Institute NPC, South Africa

Work Package 2: Clinical Study

Clinical Study

OBJECTIVES
To screen, enroll, treat, and evaluate patients as described in the study protocol.

DESCRIPTION OF WORK TO BE CONDUCTED
All clinical sites will screen and enroll patients and perform study evaluations. As lead, Aurum will also prepare the study protocol and supervise monitoring activities to ensure study start (including site assessments and initiation visits), execution (including monitoring assessments using a risk-based system), and close-out (including data cleaning and archiving) conform to protocol specifications and international standards.

RESPONSIBLE ORGANISATIONS

Work Package 3: Data Management and Statistics

Clinical Study

OBJECTIVES
To facilitate accurate data collection, monitoring, and analysis.

DESCRIPTION OF WORK TO BE CONDUCTED
The LMU data management team will create and execute Data Management Plan, develop Case Report Forms (CRFs). LMU will work with TECRO research, a South African CRO, to build and maintain study database (eCRF with build in edit-checks), and perform ongoing data cleaning in which they will identify and query data discrepancies for resolution by sites, merge and reconcile external data [eg, lab results] with clinical database. The LMU Stats team will finalize the Statistical Analysis Plan, prepare periodic reports of study data to assist the DSMB during the study assessment process, perform the statistical analysis of the multiple end points, prepare final reports for publication of results in scientific presentations and manuscripts, and summarize data for future meta-analysis projects and also assisting in modelling tasks. Other sites (including clinical and PK) will record and transmit study data.

RESPONSIBLE ORGANISATIONS

Work Package 4: Dissemination and Exploitation

Dissemination and Exploitation

OBJECTIVES
To communicate regarding ongoing study activities, disseminate key study findings, and exploit knowledge gained to maximize impact

DESCRIPTION OF WORK TO BE CONDUCTED
This will include creation of a project website and newsletter, writing and submission of abstracts, presentations and manuscripts, and coordination of activities with professional, normative, and governmental organizations.

RESPONSIBLE ORGANISATION

The Aurum Institute NPC, South Africa

Work Package 5: Modelling

Modelling

OBJECTIVES
To assess short and long-term population health impact.

DESCRIPTION OF WORK TO BE CONDUCTED
Working with Nick Menzies, an Associate Professor of Global Health in the Department of Global Health and Population at Harvard University`s Center for Health Decision Science to adapt a published mathematical model of TB to estimate the short-term effects of a new regimen on likelihood of cure, and the long-term population health benefits, compared to standard of care to the populations of South Africa and Mozambique. The initial modelling will use data from the Gates TB-HDT study to identify key data and components with greatest uncertainty. This will inform the final protocol for the clinical trial as well as the updated modelling, which will use data collected in this trial.

RESPONSIBLE ORGANISATION

The Aurum Institute NPC, South Africa

Work Package 6: Pharmacokinetics (PK)

Pharmacokinetics (PK)

OBJECTIVES
To determine sutezolid PK in plasma using sparse sampling, and to analyze the PK/PD relationship

DESCRIPTION OF WORK TO BE CONDUCTED
RUMC will assist in determining the optimal timing for collection of samples for sutezolid PK based on data from the SUDOCU study. Plasma samples will be shipped from clinical sites to RUMC, who will use previously validated methods to analyze concentrations of sutezolid and U-603. They will also use a previously validated PK model to predict exposures based these sparse samples. An initial sample of the first 10 subjects will be analyzed early in the study. A second sample of all remaining subjects will be examined later in the study. Findings will be examined in relation to study outcomes (efficacy and safety).

RESPONSIBLE ORGANISATION

Radboud umc, Netherlands

Work Package 7: Chemistry, Manufacturing and Control (CMC)

Chemistry, Manufacturing and Control (CMC)

OBJECTIVES
To synthesize drug substance and manufacture 200,000 sutezolid 200mg tablets under GMP conditions for use in the trial.

DESCRIPTION OF WORK TO BE CONDUCTED
Aurum and Sequella jointly identified TB Alliance as the suitable vendor(s) to synthesize, tablet, package, and stability test sutezolid tablets. The tablets were developed at Piramal Pharma Limited in India at using TB Alliance methods.

RESPONSIBLE ORGANISATIONS

This project [RIA2019AMR-2647] is part of the EDCTP2 Programme supported by the European Union