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Autism Innovative Medicine Studies – 2 – Trials

Fact Sheet

Reporting

Results

Project information

AIMS-2-TRIALS

Grant agreement ID: 777394

Project website

Status

Ongoing project

Start date

1 June 2018
End date

31 May 2023

Funded under:

H2020-EU.3.1.7.

Overall budget:

€ 113 274 914,75
EU contribution

€ 54 999 998,75

Coordinated by:

KING'S COLLEGE LONDON

United Kingdom

Objective

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition affecting over five million people in the European Union. The combination of core symptoms (deficits in social-communication and repetitive and restricted behaviours and interests) and common comorbidities (e.g. epilepsy and depression) significantly reduces the quality of life and life-span of affected individuals. Currently there are no effective drug treatments for the core symptoms. Key factors that have hampered progress include; 1) limited understanding of the underlying pathophysiolog(ies); 2) lack of successful translation from animal models to humans; 3) testing of drugs with specific actions in biologically heterogeneous populations; 4) limited expertise of many European ASD centres in running large-scale clinical trials; and 5) trial designs (e.g. placebo effects).

Our vision, therefore, is to apply a precision medicine approach to ASD and improve patient outcomes by tailoring treatments to a patient’s biological profile. Our efforts will build on the achievements of 5 other IMI initiatives, 4 Horizon 2020 networks, and 6 SMEs for the first time to; 1) align global resources to validate and qualify stratification biomarkers from infancy to adulthood; 2) develop objective outcome measures that can be used in trials; 3) create a European-wide clinical trials network that reliably carries out studies able to support filings to the EMA/FDA; 4) carry out better targeted clinical trials linked to other international efforts – including quick wins or “fast fails” of ineffective agents; 5) translate molecular mechanisms and drug effects between preclinical models and particular subtypes of ASD.

Together we will bring Europe to the forefront of clinical research in ASD. Also we will provide a sustainable legacy that is accessible by others across the world, attracts industry into ASD, and helps transform healthcare.

Programme(s)

H2020-EU.3.1.7. - Innovative Medicines Initiative 2 (IMI2)

Topic(s)

IMI2-2016-10-08 - Personalised medicine approaches in autism spectrum disorders

Call for proposal

H2020-JTI-IMI2-2016-10-two-stage

See other projects for this call

Funding Scheme

IMI2-RIA - Research and Innovation action

Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Coordinator

KING'S COLLEGE LONDON

Address

Strand
Wc2r 2ls London

United Kingdom

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 20 598 874,25

Website

Contact the organisation

Participants (47)

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F. HOFFMANN-LA ROCHE AG

Switzerland

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE

United Kingdom

EU Contribution

€ 2 808 026,25

STICHTING KATHOLIEKE UNIVERSITEIT

Netherlands

EU Contribution

€ 4 635 793,75

SERVICIO MADRILENO DE SALUD

Spain

EU Contribution

€ 5 411 635

INSTITUT PASTEUR

France

EU Contribution

€ 2 817 986,25

UNIVERSITAT BASEL

Switzerland

EU Contribution

€ 1 205 000

ZENTRALINSTITUT FUER SEELISCHE GESUNDHEIT

Germany

EU Contribution

€ 924 135

BIOSCI CONSULTING BVBA

Belgium

EU Contribution

€ 192 343,75

RIJKSUNIVERSITEIT GRONINGEN

Netherlands

EU Contribution

€ 837 500

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

United Kingdom

EU Contribution

€ 805 000

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

EU Contribution

€ 851 500

THE UNIVERSITY OF EDINBURGH

United Kingdom

EU Contribution

€ 245 000

ASSISTANCE PUBLIQUE HOPITAUX DE PARIS

France

EU Contribution

€ 236 625

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Ireland

EU Contribution

€ 392 346,25

BIRKBECK COLLEGE - UNIVERSITY OF LONDON

United Kingdom

EU Contribution

€ 2 899 831,25

STICHTING BURO ECNP

Netherlands

EU Contribution

€ 187 498,75

NOLDUS INFORMATION TECHNOLOGY BV

Netherlands

EU Contribution

€ 272 500

ARTTIC

France

EU Contribution

€ 549 525

DEMCON ADVANCED MECHATRONICS ENSCHEDE B.V.

Netherlands

EU Contribution

€ 482 500

KAROLINSKA INSTITUTET

Sweden

EU Contribution

€ 1 175 481,10

JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN

Germany

EU Contribution

€ 783 500

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Netherlands

EU Contribution

€ 1 022 332,50

UNIVERSITEIT GENT

Belgium

EU Contribution

€ 958 462,35

UNIVERSITY OF NEWCASTLE UPON TYNE

United Kingdom

EU Contribution

€ 245 000

UNIVERSITAET ULM

Germany

EU Contribution

€ 805 577,50

CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE TOURS

France

EU Contribution

€ 24 125

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN

Germany

EU Contribution

€ 202 500

Fondazione Stella Maris

Italy

EU Contribution

€ 68 125

UNIVERSIDAD DE SALAMANCA

Spain

EU Contribution

€ 68 125

UNIVERSITY OF GLASGOW

United Kingdom

EU Contribution

€ 245 000

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES

France

EU Contribution

€ 916 023,75

UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS

Germany

EU Contribution

€ 68 125

STELLENBOSCH UNIVERSITY

South Africa

EU Contribution

€ 419 543,75

UPPSALA UNIVERSITET

Sweden

EU Contribution

€ 149 995

UNIVERSIDADE DE COIMBRA

Portugal

EU Contribution

€ 780 299,80

FUNDAZIOA POLICLINICA GIPUZKOA FUNDACION

Spain

EU Contribution

€ 68 125

FUNDACIO CLINIC PER A LA RECERCA BIOMEDICA

Spain

EU Contribution

€ 203 125

JANSSEN PHARMACEUTICA NV

Belgium

NOVARTIS PHARMA AG

Switzerland

UCB BIOPHARMA SRL

Belgium

TEVA PHARMACEUTICAL INDUSTRIES LIMITED

Israel

AUTISM SPEAKS INC. NON PROFIT CORPORATION

United States

THE SIMONS FOUNDATION, INC

United States

AUTISTICA

United Kingdom

AUTISME-EUROPE AISBL

Belgium

EU Contribution

€ 268 600

UNIVERSITY OF BRISTOL

United Kingdom

EU Contribution

€ 51 812,50

STARLAB BARCELONA SL

Spain

EU Contribution

€ 122 500

Project information

AIMS-2-TRIALS

Grant agreement ID: 777394

Project website

Status

Ongoing project

Start date

1 June 2018
End date

31 May 2023

Funded under:

H2020-EU.3.1.7.

Overall budget:

€ 113 274 914,75
EU contribution

€ 54 999 998,75

Coordinated by:

KING'S COLLEGE LONDON

United Kingdom

Project information

AIMS-2-TRIALS

Grant agreement ID: 777394

Project website

Status

Ongoing project

Start date

1 June 2018
End date

31 May 2023

Funded under:

H2020-EU.3.1.7.

Overall budget:

€ 113 274 914,75
EU contribution

€ 54 999 998,75

Coordinated by:

KING'S COLLEGE LONDON

United Kingdom

Periodic Reporting for period 1 - AIMS-2-TRIALS (Autism Innovative Medicine Studies – 2 – Trials)

Reporting period: 2018-06-01 to 2019-05-31

Summary of the context and overall objectives of the project

Currently, there are no effective medical treatments for the core features of autism and effective therapies for frequent associated features (anxiety, depression, sleep, epilepsy) are limited. Autistic individuals and families who are seeking treatment frequently use costly nonevidence based interventions. Developing effective therapies for autism has been challenging because of the considerable diversity among autistic individuals and a limited understanding of the underlying biological mechanisms. Thus, AIMS-2-TRIALS is working towards generating new treatment options for core and associated features. With this objective, we have defined the following aims: 1) To improve our understanding of the mechanisms underpinning core and associated features of autism, and to translate these findings into clinical practice 2) To identify early neurodevelopmental pathways that modify a child’s clinical and behavioural outcome 3) To provide biomarkers that can identify and separate autistic individuals into more biologically similar subgroups to select specific treatment option for individuals with particular neurobiological profiles 4) To create objective outcome measures (i.e. instruments that are sensitive to change in core and associated features of autism) to measure the effectiveness of particular treatments 5) To test a variety of potential treatments in clinical trials 6) To partner with stakeholders including autistic people and families, clinicians, policymakers, regulators and payers to identify the barriers to testing and adopting new treatments 7) To create a scientific legacy to ensure that our databases, medical devices and products are open to others and sustainable after the life of the project.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In terms of aim 1, we have analysed our data across various levels of inference: from genetic to molecular and cellular levels, to brain circuits, cognitive differences and clinical features. For example, we have sequenced all of our DNA samples using single nucleotide polymorphism (SNP) analysis (i.e. information about single genetic building block substitutions occurring between individuals) and we also calculated genetic scores, which can indicate the extent to which a specific individual is predisposed to certain autistic traits. For aim 2, we have set up protocols for our PHENOCADES study (siblings of infants that have diagnosed autism), and data-collection and preliminary analysis for this project has started. We are working towards establishing environmental likelihood/resilience factors (e.g. pre-natal factors (i.e. maternal infection and diet) through setting up a research study in South Africa (SPS-AIMS) associated with brain development, cognition and presence/severity of clinical features. For aim 3, we have analysed data at multiple levels of inference (e.g. genetic, EEG, MRI, fMRI, DTI, clinical symptomatology and, cognition). We collaborated with colleagues in the USA to submit a letter of intent to the FDA and have had our joint work accepted by the FDA into their biomarker development program. This is the first time that this has been achieved by an academic consortium in autism. We are now preparing to submit our work to the EMA. The initial results from biomarker work are: 1) Our resting state-fMRI analysis demonstrated reduced functional connectivity in sensory-motor regions, alongside increased functional connectivity in prefrontal and parietal cortices. These differences were associated with core autism features related to communication and daily living skills. Importantly, we replicated these findings in 4 separate international cohorts containing over 2000 individuals; and obtained proof of concept that differences in brain functional connectivity can be modified by specific pharmacological compounds (even in adults) 2). Another promising result is the electrophysiological responses to pictures of upright and inverted faces – we found that some autistic individuals had differences in the timing of the EEG response to faces – this finding is also replicated by the ABC-CT consortium. We also found proof of concept that these differences predict clinical outcome ~ 2 years later. For aim 4, we are developing remote monitoring for people with autism to assess clinical change. These include measures of language and communication skills, a working memory task, and a learning task involving cooperation with a remote agent. Through working closely with industry and autistic people we have already developed a ‘wearable’ device, and this is being incorporated into our first clinical trial. For aim 5, we are testing new medicines. To support this aim, we have established a European-wide AIMS-2-TRIALS Clinical Trials Network (CTN) which includes 118 sites across 37 countries with access to >20,000 new patients per year. In our first year we have worked closely with a charity and industry to identify and train sites for our first clinical trial, link our work to another network in North America in order to increase the study size, identified the medication to be tested (arbaclofen), showed that this drug can impact on EEG and imaging biomarkers in a dose dependant manner, and registered our clinical-trials protocol. The trial protocol (for the first time in autism) includes testing of both our novel EEG biomarkers and our new ‘wearable’ device. We have already obtained ethical approval in the UK and Spain, submitted our protocol for regulatory approval in Europe, and launched the trial in North America. For aim 6, we have successfully recruited a group of individuals from the autism community (autistic people, parents and carers) from across Europe (the Autism Representatives group, or A-Reps).

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We have generated the largest database of “deep-phenotyped” autistic participants in the world so far, which includes information across multiple levels of inference. Based on this (and through collaborating with autistic individuals; together with colleagues in North America, charities and industry) our work has been instrumental in having an EEG biomarker accepted into the FDA development program. Also, we incorporated that biomarker into a clinical trial that employs our new objective outcome measure. This work is underpinning multiple analysis packages to submit to the EMA. We have also created a large, highly trained CTN, which ensures researcher access to many consenting autistic individuals, thereby increasing the efficiency of clinical trials. Furthermore, by establishing the A-Reps group we have attempted to ensure that our work includes collaborative efforts and incorporates what autistic people and their families feel is beneficial and needed. Finally, one of our most significant steps forward includes the stratification markers that we are identifying helping the scientific and clinical community to form more biologically similar subgroups of autistic individuals, with the knowledge that some subgroups may better benefit from more tailored treatments.

Logo of the project AIMS-2-TRIALS

Project information

AIMS-2-TRIALS

Grant agreement ID: 777394

Project website

Status

Ongoing project

Start date

1 June 2018
End date

31 May 2023

Funded under:

H2020-EU.3.1.7.

Overall budget:

€ 113 274 914,75
EU contribution

€ 54 999 998,75

Coordinated by:

KING'S COLLEGE LONDON

Project information

AIMS-2-TRIALS

Grant agreement ID: 777394

Project website

Status

Ongoing project

Start date

1 June 2018
End date

31 May 2023

Funded under:

H2020-EU.3.1.7.

Overall budget:

€ 113 274 914,75
EU contribution

€ 54 999 998,75

Coordinated by:

KING'S COLLEGE LONDON

United Kingdom

Project information

AIMS-2-TRIALS

Grant agreement ID: 777394

Project website

Status

Ongoing project

Start date

1 June 2018
End date

31 May 2023

Funded under:

H2020-EU.3.1.7.

Overall budget:

€ 113 274 914,75
EU contribution

€ 54 999 998,75

Coordinated by:

KING'S COLLEGE LONDON

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Last update: 30 March 2020

Record number: 218658

Permalink: https://cordis.europa.eu/project/id/777394

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Periodic Reporting for period 1 - AIMS-2-TRIALS (Autism Innovative Medicine Studies – 2 – Trials)

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CORDIS

Project information

Objective

Coordinator

Participants (47)

Project information

Project information

Periodic Reporting for period 1 - AIMS-2-TRIALS (Autism Innovative Medicine Studies – 2 – Trials)

Project information

Project information

Deliverables

Publications

Project information

Project information

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