About: AGILE-ACCORD: A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19: A structured summary of a study protocol for a randomised platform trial

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About: AGILE-ACCORD: A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19: A structured summary of a study protocol for a randomised platform trial Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	AGILE-ACCORD: A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19: A structured summary of a study protocol for a randomised platform trial
Source	Medline; PMC
abstract	OBJECTIVES: Phase I - To determine the optimal dose of each candidate (or combination of candidates) entered into the platform. Phase II - To determine the efficacy and safety of each candidate entered into the platform, compared to the current Standard of Care (SoC), and recommend whether it should be evaluated further in a later phase II & III platforms. TRIAL DESIGN: AGILE-ACCORD is a Bayesian multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19. Designed as a master protocol with each candidate being evaluated within its own sub-protocol (Candidate Specific Trial (CST) protocol), randomising between candidate and SoC with 2:1 allocation in favour of the candidate (N.B the first candidate has gone through regulatory approval and is expected to open to recruitment early summer 2020). Each dose will be assessed for safety sequentially in cohorts of 6 patients. Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort. PARTICIPANTS: Patient populations can vary between CSTs, but the main eligibility criteria include adult patients (≥18 years) who have laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We will include both severe and mild-moderate patients defined as follows: Group A (severe disease) - patients with WHO Working Group on the Clinical Characteristics of COVID-19 infection 9-point ordinal scale of Grades 4 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, non-invasive ventilation or high flow oxygen), 6 (hospitalised, intubation and mechanical ventilation) or 7 (hospitalised, ventilation and additional organ support); Group B (mild-moderate disease) - ambulant or hospitalised patients with peripheral capillary oxygen saturation (SpO(2)) >94% RA. If any CSTs are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible. Participants will be recruited from England, North Ireland, Wales and Scotland. INTERVENTION AND COMPARATOR: Comparator is the current standard of care (SoC), in some CSTs plus placebo. Candidates that prevent uncontrolled cytokine release, prevention of viral replication, and other anti-viral treatment strategies are at various stages of development for inclusion into AGILE-ACCORD. Other CSTs will be added over time. There is not a set limit on the number of CSTs we can include within the AGILE-ACCORD Master protocol and we will upload each CST into this publication as each opens to recruitment. MAIN OUTCOMES: Phase I: Dose limiting toxicities using Common Terminology Criteria for Adverse Events v5 Grade ≥3 adverse events. Phase II: Agreed on a CST basis depending on mechanism of action of the candidate and patient population. But may include; time to clinical improvement of at least 2 points on the WHO 9-point category ordinal scale [measured up to 29 days from randomisation], progression of disease (oxygen saturation (SaO(2)) <92%) or hospitalization or death, or change in time-weighted viral load [measured up to 29 days from randomisation]. RANDOMISATION: Varies with CST, but default is 2:1 allocation in favour of the candidate to maximise early safety data. BLINDING (MASKING): For the safety phase open-label although for some CSTs may include placebo or SoC for the efficacy phase. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Varies between CSTs. However simulations have shown that around 16 participants are necessary to determine futility or promise of a candidate at a given dose (in efficacy evaluation alone) and between 32 and 40 participants are required across the dose-finding and efficacy evaluation when capping the maximum number of participants contributing to the evaluation of a treatment at 40. TRIAL STATUS: Master protocol version number v5 07 May 2020, trial is in setup with full regulatory approval and utilises several digital technology solutions, including Medidata’s Rave EDC [electronic data capture], RTSM for randomisation and patient eConsent on iPads via Rave Patient Cloud. The recruitment dates will vary between CSTs but at the time of writing no CSTs are yet open for recruitment. TRIAL REGISTRATION: EudraCT 2020-001860-27 14(th) March 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
has issue date	2020-06-19(xsd:dateTime)
bibo:doi	10.1186/s13063-020-04473-1
bibo:pmid	32560744
has license	cc-by
sha1sum (hex)	a9c1bcfffbd312586072c2e4e0e10307e5620c4f
schema:url	https://doi.org/10.1186/s13063-020-04473-1
resource representing a document's title	AGILE-ACCORD: A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19: A structured summary of a study protocol for a randomised platform trial
has PubMed Central identifier	PMC7303573
has PubMed identifier	32560744
schema:publication	Trials
resource representing a document's body	covid:a9c1bcfffbd312586072c2e4e0e10307e5620c4f#body_text
is schema:about of	named entity 'Safety' named entity '8 days' named entity 'ordinal scale' named entity 'control group' named entity 'antiviral therapies' named entity 'gynaecologist' named entity 'Bayesian model' named entity 'CST' named entity 'trial protocol' named entity 'Urea' named entity 'causal relationship' named entity 'hazard ratio' named entity 'Bayesian' named entity 'University of Oxford' named entity '2-step' named entity 'risk assessment' named entity 'CST' named entity 'phase III' named entity 'mechanical ventilation' named entity 'CST' named entity 'WHO' named entity 'medical record' named entity 'NHS Trusts' named entity 'China' named entity 'CST' named entity 'renal replacement therapy' named entity 'control group' named entity 'adverse event' named entity 'follow-up' named entity 'toxicity' named entity 'sample size' named entity 'trial protocol' named entity 'lacks capacity' named entity 'SAEs' named entity 'CST' named entity 'follow-up' named entity 'premature ovarian failure' named entity 'life-threatening' named entity 'fatigue' named entity 'PCR' named entity 'coronavirus' named entity 'ordinal scale' named entity 'COVID' named entity 'clinical trials' named entity 'throat swab' named entity 'CST' named entity 'dose-finding' named entity 'Medical History' named entity 'dose-finding' named entity 'therapeutic agents' named entity 'precautionary measure' named entity 'pre-existing condition' named entity 'probability' named entity 'contraception' named entity 'toxicity' named entity 'treatment compliance' named entity 'pregnancy' named entity 'sample size' named entity 'clinical setting' named entity 'Subgroup analyses' named entity 'RRT' named entity 'viral titers' named entity 'medical history' named entity 'CSTs' named entity 'primary endpoint' named entity 'phase I/II' named entity 'placebo' named entity 'Data queries' named entity 'research team' named entity 'pre-existing conditions' named entity 'adverse event' named entity 'NIHR' named entity 'probability' named entity 'throat swab' named entity 'CST' named entity 'blood count' named entity 'sexual abstinence' named entity 'eCRF' named entity '95%' named entity 'Liver Function Tests' named entity 'Common Terminology Criteria for Adverse Events' named entity 'first-in-human'

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