Periodic Reporting for period 2 - UNITE4TB (ACADEMIA AND INDUSTRY UNITED INNOVATION AND TREATMENT FOR TUBERCULOSIS)
Período documentado: 2022-06-01 hasta 2023-05-31
The UNITE4TB consortium aims to accelerate and improve the clinical evaluation of novel compounds and combinations of drugs to develop new and highly active anti-tuberculosis (TB) treatment regimens for drug-resistant (DR) and -sensitive (DS) TB. With the EFPIA and Associated Partners joining, UNITE4TB will gain access to the majority of the most innovative TB compounds, currently in late pre-clinical, clinical phase 1 and early 2 stages. The consortium will deliver an efficient, global clinical trials (CTs) network equipped to implement phase 2A and 2B/C trials that conform to the highest regulatory standards. We will integrate state-of-the-art adaptive trial designs with conventional and new biomarkers of treatment success and employ advanced pharmacokinetic (PK) and pharmacodynamic (PD) modelling techniques and artificial intelligence (AI) and machine learning (ML) techniques to select, test and deliver novel combination regimens with a high probability of success in subsequent phase 3 CTs. Thus, UNITE4TB aims to set a new standard for anti-TB regimen development, upgrading current CT methodology and enhancing the efficiency with which new regimens are delivered to the world.
The overall management, leadership, and governance structure, which was set up in year 1 of the project, continued largely unchanged in year 2. The main results achieved so far include:
-The final study protocols for the phase 2B trial (DECISION) and phase 2B/C trial (PARADIGM4TB) have been finalized including trial design, selected compounds and combinations to be tested. For PARADIGM4TB, a dedicated EMA scientific advice was sought on an initial version of the protocol and the feedback was incorporated into the final version.
-Trial sponsors (KUM for DECISION and UCL for PARADIGM4TB) have set up their trial teams. Trial sites have been assessed and approved, and subsequently clinical trial applications have been submitted to the independent ethics committee and regulatory authority of the first countries. For PARADIGM4TB, the site selection process remains ongoing and additional trial sites are expected to be included in the trial, and filing of Clinical Trial applications.
-After finalizing the early-stage target product profile (TPP) in year 1, the consortium completed the late-stage TPP in year 2 and started to concentrate on practical implementation of selected biomarkers into the planned clinical Phase 2B/C trial.
-Starting with publicly available clinical, pre-clinical, and molecular data from different research fields, ML/AI architectures are being designed in order to provide prediction of relapse-free cure, prioritisation of drug combinations for further clinical evaluation, and feedback into adaptive CT design.
-Validation of an assay covering the background drugs used in PARADIGM4TB has been finalized and transfers and validations of assays for BTZ-043 and GSK656 are ongoing.
-Optimal biomarker sampling, sampling schedule for PK analysis and pharmacogenetic sampling were defined and included in the PARADIGM4TB protocol.
-Digital Adherence Technologies (DAT) have been assessed and optimal DAT selected in year 2.
-An Ethics Advisory Board (EAB), a Scientific Advisory Board, and a Community Advisory Group have been established and are meeting on a regular basis. An internal Regulatory Advisory Board is providing guidance to relevant WPs.
-The Data Collection Platform (DCP) prototype is available and being transformed into a production DCP. In year 2, four Data Contribution Agreements have been executed with GSK, Janssen, Otsuka and TB Alliance establishing a legal framework to enable the initial flow of Background data into the project.
-A continuous flow of dissemination and exploitation occurred in year 2 through scientific publications, presentations, webinars, social media, online news sharing. Finally, the first round of interviews with key stakeholders were completed in year 2 and produced a set of ten key recommendations.
-Discussions with other TB research consortia has been continued to stimulate cross-learning, and to ensure alignment of trial design and outcomes to facilitate trial comparability. Finally, UNITE4TB organized its 2nd TB symposium that serves as a platform for the most pressing topics within the TB ecosystem to be discussed with key proponents in the field.
-The final study protocols for the phase 2B trial (DECISION) and phase 2B/C trial (PARADIGM4TB) have been finalized including trial design, selected compounds and combinations to be tested. For PARADIGM4TB, a dedicated EMA scientific advice was sought on an initial version of the protocol and the feedback was incorporated into the final version.
-Trial sponsors (KUM for DECISION and UCL for PARADIGM4TB) have set up their trial teams. Trial sites have been assessed and approved, and subsequently clinical trial applications have been submitted to the independent ethics committee and regulatory authority of the first countries. For PARADIGM4TB, the site selection process remains ongoing and additional trial sites are expected to be included in the trial, and filing of Clinical Trial applications.
-After finalizing the early-stage target product profile (TPP) in year 1, the consortium completed the late-stage TPP in year 2 and started to concentrate on practical implementation of selected biomarkers into the planned clinical Phase 2B/C trial.
-Starting with publicly available clinical, pre-clinical, and molecular data from different research fields, ML/AI architectures are being designed in order to provide prediction of relapse-free cure, prioritisation of drug combinations for further clinical evaluation, and feedback into adaptive CT design.
-Validation of an assay covering the background drugs used in PARADIGM4TB has been finalized and transfers and validations of assays for BTZ-043 and GSK656 are ongoing.
-Optimal biomarker sampling, sampling schedule for PK analysis and pharmacogenetic sampling were defined and included in the PARADIGM4TB protocol.
-Digital Adherence Technologies (DAT) have been assessed and optimal DAT selected in year 2.
-An Ethics Advisory Board (EAB), a Scientific Advisory Board, and a Community Advisory Group have been established and are meeting on a regular basis. An internal Regulatory Advisory Board is providing guidance to relevant WPs.
-The Data Collection Platform (DCP) prototype is available and being transformed into a production DCP. In year 2, four Data Contribution Agreements have been executed with GSK, Janssen, Otsuka and TB Alliance establishing a legal framework to enable the initial flow of Background data into the project.
-A continuous flow of dissemination and exploitation occurred in year 2 through scientific publications, presentations, webinars, social media, online news sharing. Finally, the first round of interviews with key stakeholders were completed in year 2 and produced a set of ten key recommendations.
-Discussions with other TB research consortia has been continued to stimulate cross-learning, and to ensure alignment of trial design and outcomes to facilitate trial comparability. Finally, UNITE4TB organized its 2nd TB symposium that serves as a platform for the most pressing topics within the TB ecosystem to be discussed with key proponents in the field.
Our ambition is to advance TB drug development by conducting innovative phase 2A and 2B/C trials that will accelerate the progress of new regimens into phase 3 trials with a high chance of success, regulatory approval, and ultimately treatment for people with DR and/or DS-TB. UNITE4TB will contribute substantially towards the goals of End TB Strategy and Sustainable Development Goals (SDG) and addresses the emergence of DR-TB by developing new treatments.
Expected results of UNITE4TB include:
-New regimen(s) selected for phase 3 trials.
-Innovative multi-arm multi-stage (MAMS) trial design, with analyses-driven decision-making throughout the process and including stratification for disease severity.
-New endpoints in phase 2A trials to quantify change in bacterial load.
-Investigation of truncated treatment regimens with an early relapse endpoint
-Exploration of biomarkers for the predication of relapse-free cure.
-PK/PD modelling in 2A and 2B/C trials, to define optimal doses and to complement the primary outcome analysis of early relapse.
-AI/ML to predict relapse-free cure, prioritise treatment regimens and optimise design for phase 2C or 3 clinical trials.
The main potential impacts of the project are:
-Providing new tools and understanding on how to progress TB science for the discovery and development of new clinical candidates and combinations thereof across the TB R&D landscape with special emphasis on innovative clinical trial design and development of novel biomarkers.
-Contributing to the EU’s ambition of being a ‘best practice region’ for addressing AMR, and profit from its medical capacity to individualize and implement into medical practice combination therapies addressing MDR/XDR.
-Developing new knowledge and tools, innovative clinical trial designs, imaging technology, biomarkers and pharmacogenomics diagnostics and exploiting AI for the development of new clinical candidates and combinations.
-Enabling the progression of potential new safe, efficacious, shorter, and affordable treatment solutions for people with TB worldwide, with the intent to improve quality of life and life expectancy.
-Contributing to the development of a vibrant TB research environment in the EU, fostering private-public collaboration across EFPIA, Academia, NGO’s and SME’s and strengthening the competitiveness and industrial leadership of Europe
-Providing a legal frame and agreement on IP terms and exploitation, as paradigm of public and private international collaboration in the development of combination regimens.
-Implementing agreements with other consortia facilitating prompt data exploitation, including data sharing with the external TB research community to accelerate future TB drug regimen development.
-Act as a platform for TB drug development breakthroughs beyond the lifetime of the project and set-up of smaller partnerships specifically designed to progress individual compounds/regimens.
-Awareness of regulators, policy makers, and future procurers on the UNITE4TB project, goals and findings in support of future policy development.
Expected results of UNITE4TB include:
-New regimen(s) selected for phase 3 trials.
-Innovative multi-arm multi-stage (MAMS) trial design, with analyses-driven decision-making throughout the process and including stratification for disease severity.
-New endpoints in phase 2A trials to quantify change in bacterial load.
-Investigation of truncated treatment regimens with an early relapse endpoint
-Exploration of biomarkers for the predication of relapse-free cure.
-PK/PD modelling in 2A and 2B/C trials, to define optimal doses and to complement the primary outcome analysis of early relapse.
-AI/ML to predict relapse-free cure, prioritise treatment regimens and optimise design for phase 2C or 3 clinical trials.
The main potential impacts of the project are:
-Providing new tools and understanding on how to progress TB science for the discovery and development of new clinical candidates and combinations thereof across the TB R&D landscape with special emphasis on innovative clinical trial design and development of novel biomarkers.
-Contributing to the EU’s ambition of being a ‘best practice region’ for addressing AMR, and profit from its medical capacity to individualize and implement into medical practice combination therapies addressing MDR/XDR.
-Developing new knowledge and tools, innovative clinical trial designs, imaging technology, biomarkers and pharmacogenomics diagnostics and exploiting AI for the development of new clinical candidates and combinations.
-Enabling the progression of potential new safe, efficacious, shorter, and affordable treatment solutions for people with TB worldwide, with the intent to improve quality of life and life expectancy.
-Contributing to the development of a vibrant TB research environment in the EU, fostering private-public collaboration across EFPIA, Academia, NGO’s and SME’s and strengthening the competitiveness and industrial leadership of Europe
-Providing a legal frame and agreement on IP terms and exploitation, as paradigm of public and private international collaboration in the development of combination regimens.
-Implementing agreements with other consortia facilitating prompt data exploitation, including data sharing with the external TB research community to accelerate future TB drug regimen development.
-Act as a platform for TB drug development breakthroughs beyond the lifetime of the project and set-up of smaller partnerships specifically designed to progress individual compounds/regimens.
-Awareness of regulators, policy makers, and future procurers on the UNITE4TB project, goals and findings in support of future policy development.