scholarly journals EDITORIAL: IS NOW THE TIME FOR COMBINATION THERAPIES FOR ALZHEIMER DISEASE?

2019 ◽  
pp. 1-2
Author(s):  
J.C. Morris
Keyword(s):  
Clinical Trials ◽  
Alzheimer Disease ◽  
Amyloid Beta ◽  
Task Force ◽  
Human Monoclonal Antibody ◽  
The European Union ◽  
Combination Therapies ◽  
Phase 3 ◽  
Amyloidogenic Peptides ◽  
The Eu

In this issue, Gauthier and colleagues from the European Union-North America Clinical Trials in Alzheimer Disease Task Force (EU/US CTAD Task Force) provide a compelling argument for the implementation of clinical trials in persons with Alzheimer disease (AD) dementia that utilize combinations of experimental anti-Alzheimer therapies (1). The rationale for combination therapy in AD rests on the appreciation that AD pathophysiology is complex and involves many pathogenic pathways (2). The EU/US CTAD Task Force recommends that combination therapies should include therapies that target various aspects of the process wherein amyloid precursor protein undergoes proteolytic cleavage to produce amyloidogenic peptides. That anti-amyloid monotherapy alone is insufficient to provide clinical benefit with AD dementia has been underscored once again by the recent decision of Biogen and Eisai to discontinue Phase 3 studies of aducanumab, a human monoclonal antibody that targets aggregated forms of amyloid-beta, because futility analyses indicated that the trials were unlikely to meet their primary endpoint (3); similarly, Roche has announced discontinuation of trials of crenezumab (4). The EU/US CTAD Task Force nonetheless recommends that therapies that target amyloid-beta should be considered for inclusion in combination clinical trials in AD dementia, given the preponderance of evidence that disruptions in amyloid-beta production, clearance, or processing are very likely to be involved with, or even initiate, AD pathogenesis (5).

COMMENTARY: COMBINATION THERAPY FOR ALZHEIMER’S DISEASE: PERSPECTIVES OF THE EU/US CTAD TASK FORCE

2019 ◽  
pp. 1-2
Author(s):  
E. Siemers
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
European Union ◽  
Clinical Trials ◽  
Task Force ◽  
Pharmaceutical Companies ◽  
The European Union ◽  
Combination Therapies ◽  
Regulatory Pathways ◽  
The Eu

In October 2018, the European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) met to discuss an increasingly important topic, the scientific, regulatory, and logistical challenges to the development of combination therapies for AD. Challenges related to ever-changing scientific knowledge, challenges related to complex regulatory pathways and challenges related to the necessity for pharmaceutical companies to collaborate must all be addressed. These challenges must be met since task Force members unanimously agreed that successful treatment of AD will likely require combination therapies targeting multiple mechanisms and pathways.

COMBINATION THERAPY FOR ALZHEIMER’S DISEASE: PERSPECTIVES OF THE EU/US CTAD TASK FORCE

2019 ◽  
pp. 1-5
Author(s):  
S. Gauthier ◽  
J. Alam ◽  
H. Fillit ◽  
T. Iwatsubo ◽  
H. Liu-Seifert ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
European Union ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Successful Treatment ◽  
Task Force ◽  
The European Union ◽  
Accelerate Development ◽  
The Eu

Combination therapy is expected to play an important role for the treatment of Alzheimer’s disease (AD). In October 2018, the European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) met to discuss scientific, regulatory, and logistical challenges to the development of combination therapy for AD and current efforts to address these challenges. Task Force members unanimously agreed that successful treatment of AD will likely require combination therapy approaches that target multiple mechanisms and pathways. They further agreed on the need for global collaboration and sharing of data and resources to accelerate development of such approaches.

scholarly journals THE FUTURE OF ANTI-AMYLOID TRIALS

2020 ◽  
pp. 1-6
Author(s):  
P.S. Aisen ◽  
J. Cummings ◽  
R. Doody ◽  
L. Kramer ◽  
S. Salloway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Task Force ◽  
Safety Concern ◽  
Combination Therapies ◽  
Interim Analyses ◽  
New Biomarkers ◽  
Insight Into ◽  
The Eu

The termination of many clinical trials of amyloid-targeting therapies for the treatment of Alzheimer’s disease (AD) has had a major impact on the AD clinical research enterprise. However, positive signals in recent studies have reinvigorated support for the amyloid hypothesis and amyloid-targeting strategies. In December 2019, the EU-US Clinical Trials on Alzheimer’s Disease (CTAD) Task Force met to share learnings from these studies in order to inform future trials and promote the development of effective AD treatments. Critical factors that have emerged in studies of anti-amyloid monoclonal antibody therapies include developing a better understanding of the specific amyloid species targeted by different antibodies, advancing our insight into the mechanism by which those antibodies may reduce pathology, implementing more comprehensive repertoires of biomarkers into trials, and identifying appropriate doses. Studies suggest that Amyloid-Related Imaging Abnormalities – effusion type (ARIA-E) are a manageable safety concern and that caution should be exercised before terminating studies based on interim analyses. The Task Force concluded that opportunities for developing effective treatments include developing new biomarkers, intervening in early stages of disease, and use of combination therapies.

scholarly journals Methodological Characteristics of Clinical Trials Supporting the Marketing Authorisation of Advanced Therapies in the European Union

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolina Iglesias-Lopez ◽  
Antònia Agustí ◽  
Antonio Vallano ◽  
Merce Obach
Keyword(s):  
European Union ◽  
Clinical Trials ◽  
Added Value ◽  
Life Cycle Approach ◽  
The European Union ◽  
Open Label ◽  
Advanced Therapy ◽  
Advanced Therapies ◽  
Number Of Patients ◽  
The Eu

Several advanced therapy medicinal products (ATMPs) have been approved in the European Union (EU). The aim of this study is to analyse the methodological features of the clinical trials (CT) that supported the marketing authorization (MA) of the approved ATMPs in the EU. A systematic review of the characteristics of pivotal CT of ATMPs approved in the EU until January 31st, 2021 was carried out. A total of 17 ATMPs were approved and 23 CT were conducted to support the MA (median, 1, range, 1–3). Of those studies, 8 (34.78%) were non-controlled and 7 (30.43%) used historical controls. Only 7 (30.4%) were placebo or active-controlled studies. Among all CT, 21 (91.3%) were open-label and 13 (56.52%) had a single-arm design. To evaluate the primary endpoint, 18 (78.26%) studies used an intermediate and single variable. The median (IQR) number of patients enrolled in the studies was 75 (22–118). To date, ATMPs’ approval in the EU is mainly supported by uncontrolled, single-arm pivotal CT. Although there is a trend toward an adaptive or a life cycle approach, a switch to more robust clinical trial designs is expected to better define the benefit and the therapeutic added value of ATMPs.

scholarly journals PLASMA BIOMARKERS OF AD EMERGING AS ESSENTIAL TOOLS FOR DRUG DEVELOPMENT: AN EU/US CTAD TASK FORCE REPORT

2019 ◽  
pp. 1-5
Author(s):  
R.J. Bateman ◽  
K. Blennow ◽  
R. Doody ◽  
S. Hendrix ◽  
S. Lovestone ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Task Force ◽  
Accurate Estimate ◽  
Current Status ◽  
The European Union ◽  
Neurofilament Light ◽  
Stakeholder Collaboration ◽  
Task Force Report

There is an urgent need to develop reliable and sensitive blood-based biomarkers of Alzheimer’s disease (AD) that can be used for screening and to increase the efficiency of clinical trials. The European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) discussed the current status of blood-based AD biomarker development at its 2018 annual meeting in Barcelona, Spain. Recent improvements in technologies to assess plasma levels of amyloid beta indicate that a single sample of blood could provide an accurate estimate of brain amyloid positivity. Plasma neurofilament light protein appears to provide a good marker of neurodegeneration, although not specific for AD. Plasma tau shows some promising results but weak or no correlation with CSF tau levels, which may reflect rapid clearance of tau in the bloodstream. Blood samples analyzed using -omics and other approaches are also in development and may provide important insight into disease mechanisms as well as biomarker profiles for disease prediction. To advance these technologies, international multidisciplinary, multi-stakeholder collaboration is essential.

scholarly journals Preclinical Alzheimer Disease Drug Development: Early Considerations Based on Phase 3 Clinical Trials

2020 ◽  
Vol 26 (7) ◽  
pp. 888-900
Author(s):  
Anna Hung ◽  
Monika Schneider ◽  
Marianne Hamilton Lopez ◽  
Mark McClellan
Keyword(s):  
Clinical Trials ◽  
Alzheimer Disease ◽  
Drug Development ◽  
Phase 3

scholarly journals IDENTIFYING BETTER OUTCOME MEASURES TO IMPROVE TREATMENT OF AGITATION IN DEMENTIA: A REPORT FROM THE EU/US/CTAD TASK FORCE

2018 ◽  
pp. 1-5
Author(s):  
M. Sano ◽  
M. Soto ◽  
M. Carrillo ◽  
J. Cummings ◽  
S. Hendrix ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Outcome Measures ◽  
Primary Outcome ◽  
Task Force ◽  
Neuropsychiatric Symptoms ◽  
Training And Education ◽  
The Past ◽  
Global Ratings ◽  
Power Studies ◽  
The Eu

For the second time in the past 3 years, the EU-US CTAD Task Force addressed challenges related to designing clinical trials for agitation in dementia, which is one of the most disruptive aspects of the condition for both patients and caregivers. Six recommendations emerged from the Task Force meeting: 1 – Operationalizing agitation criteria established by the IPA; 2 – Combining clinician- and caregiver-derived outcomes as primary outcome measures; 3 – Using global ratings to define clinically meaningful effects and power studies; 4 – Improving the accuracy of caregiver reports by better training and education of caregivers; 5 – Employing emerging technologies to collect near real-time behavioral data; and 6 – Utilizing innovative trial designs and increasing the use of biomarkers to maximize the productivity of clinical trials for neuropsychiatric symptoms.

scholarly journals Response to hybrid threats: peculiarities of the European Union strategy on countering the disinformation

2020 ◽  
Vol 10 (27) ◽  
pp. 106-116
Author(s):  
Lesia Dorosh ◽  
Keyword(s):  
Task Force ◽  
Public Awareness ◽  
Legal Framework ◽  
Practical Training ◽  
The European Union ◽  
Alert System ◽  
Code Of Practice ◽  
Hybrid Threats ◽  
Rapid Alert System ◽  
The Eu

The features of the European Union’s comprehensive strategy on countering the disinformation have been analyzed. It is emphasized on the creation of the legal framework and the activities of institutions aimed at countering the hybrid challenges, combating disinformation, exposing false messages and strengthening of the independent media. 10 actions of the EU to tackle the disinformation have been analyzed, such as creating the EuvsDisinfo public database, protection the integrity of EU elections, debunking Euromyths, monitoring disinformation messages with the Rapid Alert System, establishing the EU-wide Code of Practice on Disinformation, organizing events that promote media literacy, empowering civil society to both identify and expose disinformation, facilitating the work of fact-checkers, creating campaigns that raize public awareness on the disinformation’s negative effects, supporting media freedom and pluralism for a healthy democracy. The instruments of the EU in response to the hybrid threats such as the East StratCom Task Force (ESTF), the Hybrid Fusion Cell (HFC) and the Rapid Alert System - Disinformation (RAS-DIS) have been monitored. It has been determined that the EU is particularly attentive to practical training in combating hybrid threats. It is alleged that the use of a multilevel, cross-sectoral approach enables the EU to gradually increase its defence to counter modern hybrid threats. It is highlighted that Ukraine, which is suffering from the hybrid war, should involve the experience of the use of the instruments developed within the EU, adopting and sharing experience in combating disinformation and provide the resistance to hybrid challenges.

scholarly journals Platform Trials to Expedite Drug Development in Alzheimer’s Disease: A Report from the EU/US CTAD Task Force

2021 ◽  
pp. 1-7
Author(s):  
P.S. Aisen ◽  
R.J. Bateman ◽  
M. Carrillo ◽  
R. Doody ◽  
K. Johnson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Task Force ◽  
Lessons Learned ◽  
Combination Therapies ◽  
Diverse Range ◽  
Interim Analyses ◽  
Treatment Regimens ◽  
Experimental Therapies ◽  
The Eu

A diverse range of platforms has been established to increase the efficiency and speed of clinical trials for Alzheimer’s disease (AD). These platforms enable parallel assessment of multiple therapeutics, treatment regimens, or participant groups; use uniform protocols and outcome measures; and may allow treatment arms to be added or dropped based on interim analyses of outcomes. The EU/US CTAD Task Force discussed the lessons learned from the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU) platform trial and the challenges addressed by other platform trials that have launched or are in the planning stages. The landscape of clinical trial platforms in the AD space includes those testing experimental therapies such as DIAN-TU, platforms designed to test multidomain interventions, and those designed to streamline trial recruitment by building trial-ready cohorts. The heterogeneity of the AD patient population, AD drugs, treatment regimens, and analytical methods complicates the design and execution of platform trials, yet Task Force members concluded that platform trials are essential to advance the search for effective AD treatments, including combination therapies.

Regulation of Clinical Trials

2021 ◽  
pp. 195-212
Keyword(s):  
Clinical Trial ◽  
European Union ◽  
Information System ◽  
Clinical Trials ◽  
Well Being ◽  
The European Union ◽  
Approval Process ◽  
Clinical Trials Regulation ◽  
Clinical Trial Information ◽  
The Eu

This chapter discusses the publication of the European Clinical Trials Directive in 2001 and its incorporation into the law of Member States. It explores the intention of the Directive in harmonising the rules for conducting clinical trials within the EU to facilitate the internal market in medicinal products and to protect the rights, safety, and well-being of participants. It also covers the passing of the new Clinical Trials Regulation (CTR) by the EU in 2014, which was prompted by concern that the system for approving clinical trials was overly bureaucratic and that it was hampering multinational trials. The CTR could not come into force until the Clinical Trial Information System (CTIS), which is intended to provide a single coordinated approval process, became fully functional. This happened too late for the CTR to be automatically incorporated into UK law by the European Union (Withdrawal) Act 2018.

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