WP1: 'Candidates'

Overall Objective

The overall objective of this WP is to characterise further the candidate peptide epitopes to be used in the DAVIAD vaccine. The WP will use established in vivo models to generate pharmacodynamic data in support of the CTA application and provide data for the Investigators’ Brochure.

Specific Objectives:

  • Determine the optimal posology in disease models
  • Understand the impact of co-medication on the efficacy of the DAVIAD vaccine
  • Determine the recognition of the GD peptide epitopes by human PBMC and antibodies
  • Prepare a non-clinical regulatory package to support a CTA application

WP2: 'CMC'

Overall Objective:

The overall objective of this WP is to supply GMP grade Investigational Medicinal Product (IMP) for use in toxicity studies and in a Phase I/IIa clinical programme.

Specific Objectives:

  • Develop a small scale, non-GMP manufacturing process for the individual active pharmaceutical ingredient (API) peptides
  • Develop and validate appropriate analytical methods for characterisation and release of API and Investigational Medicinal Product (IMP)
  • Establish impurity profile for API and IMP and identify stability indicating analytical methods
  • Manufacture and release GMP grade API for each peptide in the vaccine
  • Develop IMP formulation suitable for toxicity studies and Phase I/IIa clinical programme
  • Establish provisional specifications for API peptides and IMP
  • Manufacture and release sufficient IMP to support preclinical and clinical programme
  • Complete GMP stability studies on API and IMP

WP3: Toxicology'

Overall Objective:

The overall objective of this WP is to assess the effects of the DAVIAD vaccine peptides in at least one relevant toxicology model sufficient to support a Phase I/IIa clinical programme in patients with GD.

Specific Objectives:

  • To identify a relevant model for performing toxicity studies
  • Perform a GLP cardiovascular and respiratory systems safety pharmacology study
  • Perform a GLP single dose acute toxicity study
  • Perform a GLP repeat dose toxicity study
  • Perform additional non-GLP supportive toxicity studies as required

WP4: 'Regulatory'

Overall Objective:

The overall objective of this WP is to obtain regulatory approval for a Phase I /IIa clinical study in patients with GD.

Specific Objectives:

  • To obtain Scientific Advice from at least one EU national agency
  • To obtain regulatory approval for Phase I /IIa clinical trial in patients with GD
  • To apply for orphan medicinal product designations in EU and US for sight threatening GO and paediatric GD

WP5: 'Clinical Trial'

Overall Objective:

The key objectives of WP5 are to design and execute a Phase I/IIa trial in GD patients to provide a clear assessment of safety and proof of concept of efficacy.

Specific Objectives:

  • Prepare a Phase I/IIa clinical study protocol and study logistics capable of delivering the clinical study in patients with Graves’ Disease
  • Conduct the clinical study to GCP in the timelines proposed
  • Report the results and prepare a Clinical Study Report

WP6: 'Clinical Analysis Method Development'

Overall Objective:

The overall objective of this WP is to develop, validate and execute study specific clinical assays to support patient eligibility and assess secondary exploratory endpoints.

Specific Objectives:

  • Establish and validate robust analytical methods and assays for detecting antibodies to the peptides in the DAVIAD vaccine in human blood
  • Establish a robust and sensitive method to determine the PBMC proliferative response and other immune parameters to DAVIAD vaccine in patients treated with DAVIAD vaccine.
  • Develop a protocol for the clinical trial and support activities in WP5 to obtain approvals for the study.
  • Perform to GCLP all study specific clinical analytical methods and report as per the clinical trial protocol

WP7: 'Dissemination & Exploitation'

Overall Objective:

The overall objective of this WP is to make the results from the project available to the pharmaceutical industry, healthcare systems, GD patients, general public, and to ensure that the results have a route to commercialisation.

Specific Objectives:

  • Develop project website for communication and dissemination activities.
  • Publish results in International referred Journals and trade publications following GPP Guidelines.
  • Disseminate results through conferences and seminars (academic and commercial).
  • Examine routes to commercial exploitation; examine market needs and make appropriate partnerships
  • Increase European regional awareness of SMEs involved in ground-breaking projects
  • Archive relevant data and results from the project

WP8: 'Consortium Management & Reporting to the EC'

Overall Objective:

The overall objective of this WP is to provide both strategic and operational management for DAVIAD ensuring the successful completion of the project within the timescale and resources provided.

Specific Objectives:

  • Establish and implement the Steering Group, Patient Advisory Board, Ethics and Safety Advisory Board and the International Advisory Board (IAB)
  • Draw up the Project Implementation Plan and Regulation of the Consortium Agreement
  • Develop and implement Quality Management, Risk Management Plan and Conflict Resolution Procedure
  • Develop and Implement financial accounting, reporting and management mechanisms
  • Perform day-to-day project management, including assessment of results