Work Packages
A-TANGO consists of eight tightly inter-linked work packages (WPs). Briefly, WP1 will perform the tasks related to obtaining regulatory and ethical approvals. Substantial work will be performed in WP2 to ensure safe and cost-effective drug production and delivery to all clinical trial sites. The Charité will lead WP3, which will implement the clinical trial protocol in about 30 European clinical sites that are connected to EF CLIF. In WP4, the biological samples will be bio-banked and analyzed. The biomarker data obtained from the trial will then be analyzed in more detail by WP5, including data management and statistical analyses. WP6 will conduct a market analysis as a basis for business planning, exploitation, and valorisation of A-TANGO results, including a health economic analysis to estimate the cost-effectiveness and impact of G-TAK administration on quality of life, and will foster engagement with all identified stakeholders. Through WP7, A-TANGO’s aims, progress, and results will be continuously disseminated by focusing on patient and public awareness of alcohol abuse, liver disease, cirrhosis, and acute-on-chronic liver failure (ACLF). Professional project management is covered in WP8 to oversee and streamline all activities and to ensure that the project as a whole performs at a high-quality level on time and within budget. You can cruise through the different work packages and their objectives in more detail below.
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This WP deals with development of all ethics and regulatory documents and obtaining approvals for clinical trials. WP1 will pursue the following specific objectives:
- To review, manage and approve conflict of interest of involved researchers.
- To finalize the study design and protocol.
- To harmonise and finalise the IMPD and investigator brochure for submission to the competent authorities (CAs).
- To obtain regulatory approval for clinical trials to be carried out in WP3.
- To develop the quality management system (QMS) of YAQ, including bridge procedures coordinating the work between EU-partners and to consider ISO certification.
- To conclude contracts with 27 additional clinical sites to perform the trial.
- To generate all documents needed to obtain CA authorisation and ethical approval for the clinical trial and to perform the submission procedure.
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The objective of WP02 is to organize the sourcing, manufacturing, packaging, labelling, and distribution of G-CSF and TAK-242 in accordance with all relevance regulations including but not limited to Good Manufacturing Practice (GMP) and developing and using an appropriate Quality Management System (QMS). WP2 will pursue the following specific objectives:
- Selection, validation and contracting of manufacturer of two bulk active pharmaceutical ingredients (TAK-242 and G-CSF) and two placebos, to be followed by a similar process for formulating active pharmaceutical ingredients (APIs) into patient-ready dosages.
- Provision and management of all third-party testing processes of active ingredients and placebos to ensure all regulatory requirements have been met. This includes certification of conformity and analysis, conformity to regulations and stability testing (chemical, physical, functional) for all APIs and placebos and of the final patient-ready dosages.
- Sourcing of all other elements of the patient-ready kits including packaging, labelling, translations, and insert printing provision.
- Final assembly in house of patient kits, documentation and distribution of kits to trial sites, include handling and environmentally friendly disposal of returned materials.
- Expansion of current regulatory infrastructure to include implementation of new QMS.
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The objective of WP03 is to establish safety, pharmacokinetics and efficacy of G-TAK in patients with srAH and ACLF and produce meaningful advances for this group of patients with non-communicable disease so that G-TAK is ready for late stage clinical trials.WP3 will pursue the following specific objectives:
- To establish safety, pharmacokinetics and efficacy in patients with srAH and ACLF.
- To produce meaningful advances for this group of patients with srAH and ACLF.
- To hand over trial data to WP 5 to prepare G-TAK for late-stage clinical trials.
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The role of WP4 is to coordinate biobanking of clinical samples collected in the different clinical sites and to assess Pharmacokinetics (PK) data and biomarkers endpoints to a) ascertain optimal treatment delivery and; b) guide further optimisation of G-TAK regimen. There is no pre-clinical work involved in this WP or the project. WP4 will pursue the following specific objectives:
- To prepare Standard Operating Procedures (SOPs), instructions for sample collection, labelling, storage and shipping instructions and disseminate to clinical sites taking part to the study.
- To prepare and distribute reagents and SOPs for the biomarker “Ex vivo all blood LPS stimulation” to be performed by the participating clinical sites and to validate this method across these centres.
- To provide central sample biobanking facilities.
- To validate methods and conduct pharmacokinetics analyses from the first thirty patients recruited in the treatment arms for the scheduled interim analysis.
- To quantify biomarkers to assess both treatment efficacy and further optimize G-TAK regimen for late-phase clinical trials (Phase 3).
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The A-TANGO project will generate and analyse clinical and biological data from 121 patients (including 15% dropouts) to establish safety, pharmacokinetics and efficacy of G-TAK in patients with srAH and ACLF. Legally and ethically sound data management, correct integration and high-quality analysis are therefore tasks of strategic importance. WP5 will pursue the following specific objectives:
- To set the legal and ethical terms for the efficient and GDPR compliant transfer of biological materials and data to and from each of the A-TANGO partners involved in sample processing.
- To provide professional and high-quality data management services to support generation and analysis of trial data.
- To plan, conduct and summarize statistical analyses of G-TAK safety, pharmacokinetics, and efficacy.
- To analyse biomarker data.
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The key objective of prepare A-TANGO results for market roll-out and late-stage trials. This includes the following specific objectives:
- To prepare commercialization and market roll-out plans and raise commercial interest in the continued development of G-TAK to facilitate smooth entry into clinical practice.
- To exploit the trial results from a health economic perspective including impact on quality of life and incremental cost per health outcome to evaluate the value of G-TAK for insurance companies and health systems.
- To conduct market analyses for potential revenues of G-TAK and explore its commercial value for drug manufacturers with the aim to inform a business plan.
- To foster sustainability of A-TANGO results by preparing for late-stage clinical trials of G-TAK in patients with srAH and ACLF.
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The objective of WP7 is the development of a communication strategy and dissemination plan aimed at stakeholders of the EU member states, namely patients suffering from liver disease and, in particular, from cirrhosis, hepatologists, geneticists, clinicians, bio-informaticians, policy makers and politicians concerned with liver diseases, pharma and biotech companies, international professional networks and the general public. The strategy will include the following specific aims:
- To make A-TANGO known to all relevant stakeholder types.
- To inform and foster exchange with the scientific community and patient organizations.
- To disseminate to a range of stakeholder types the results of this trial and the therapeutic potential of G-TAK.
- To prepare the next generation of scientists in the field of liver research.
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Effective project management is a central element of successful research. This is because large research projects entail a lot of administrative work. The following objectives will be actively pursued by WP8:
- To make A-TANGO achieve its objectives and to deliver its milestones and deliverables in time, within budget, and in a high-quality.
- To help the consortium abide by the regulations and contractual obligations according to the grant agreement, its annexes, and the consortium agreement.
- To look after the project`s finances and to report them properly to the EC.
- To establish a communication infrastructure which enables the partners to communicate efficiently and to stay connected for the run-time of the project.
- To preserve the rights of the partners regarding intellectual property and to act as a mediator in case of disputes.