AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19

NCT ID: NCT04516759

Last Updated: 2022-04-25

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-12

Study Completion Date

2021-05-12

Brief Summary

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The ARCADIA Trial is a randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with either Type 1 or Type 2 diabetes, hospitalised with COVID-19.

Detailed Description

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The ARCADIA Trial will assess the safety and efficacy of AZD1656 in 150 patients with either Type 1 or Type 2 diabetes who have been hospitalised with COVID-19.

AZD1656 is a glucokinase (GK; hexokinase 4) activator which has been shown to reduce blood glucose for up to 4 months in humans. Diabetic patients admitted to hospital with COVID-19 often present with hyperglycaemia and are particularly vulnerable to progression to severe COVID-19. Treatment with AZD1656 (in addition to their usual care) may provide additional glucose control which could help improve clinical outcomes in both Type 1 and Type 2 diabetic populations.

In addition to its glucose lowering effect, AZD1656 may have additional benefits to COVID-19 patients via its effects on immune function. In many patients with severe COVID-19, an overreaction of the body's own immune system can cause severe problems including damage to the lungs and heart, which can lead to breathing problems necessitating intubation and ventilation. AZD1656 has been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments. This migration of Treg cells to inflamed tissue is crucial for their immune-modulatory function (Kishore et al (2017)). AZD1656 could enhance Treg migratory capacity and may prevent the development of cardiorespiratory complications observed in hospitalised patients with COVID-19, leading to lower requirements for oxygen therapy and assisted ventilation, and reduced incidences of pneumonia and acute respiratory distress syndrome (ARDS).

Diabetic patients hospitalised with COVID-19 will be randomised to receive either AZD1656 tablets or placebo tablets on a 1:1 basis until they are discharged from hospital or until they require intubation/mechanical ventilation. The aim of the study is to determine whether AZD1656 improves clinical outcomes in diabetic patients hospitalised with COVID-19. The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement will be used as the standard methodology for measuring patient outcomes.

Conditions

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Covid19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a randomised double-blind study. Eligible patients will be randomly assigned to one of two groups (AZD1656 plus usual care or placebo plus usual care) on a 1:1 basis
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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AZD1656 (plus Usual Hospital Care)

50mg film-coated tablets at a dose of 100mg BID

Group Type EXPERIMENTAL

AZD1656

Intervention Type DRUG

50mg film-coated tablets (at daily dose of 100mg BID)

Matched Placebo (plus Usual Hospital Care)

Matched placebo tablets

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matched placebo tablets

Interventions

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AZD1656

50mg film-coated tablets (at daily dose of 100mg BID)

Intervention Type DRUG

Placebo

Matched placebo tablets

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Male or Female.
2. Aged 18 and older.
3. Have either Type I or Type II Diabetes Mellitus.
4. Hospitalised with suspected or confirmed novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) infection at time of enrolment, categorised as stage 3, 4 or 5 on the WHO Ordinal Scale for Clinical Improvement.
5. Blood glucose level at or above 4 mmol/L.
6. Able to take oral (tablet) formulation of medication.
7. Patient is able to provide written informed consent prior to initiation of any study procedures.

Exclusion Criteria

1. In the opinion of the clinical team, progression to intubation or mechanical ventilation is imminent and inevitable, within the next 24 hours, irrespective of the provision of treatments.
2. Patients admitted with primary suspected or proven Mycoplasma pneumoniae, Chlamydia pneumoniae and bacterial pneumonia, who acquired COVID-19 while hospitalized.
3. Treatment with immunomodulators or anti-rejection drugs within the last 3 months.
4. Pregnant or breast feeding.
5. Men, and women of child-bearing potential, unwilling to use highly effective contraception during their participation in the trial and for 2 weeks after study completion.
6. Anticipated transfer to another hospital which is not a study site within 72 hours.
7. Known sensitivity to any of the study medication/placebo excipients.
8. Prior dosing with AZD1656 on a previous clinical trial.
9. Patients admitted as a result of and receiving immediate treatment for an acute asthmatic attack, acute myocardial infarction, acute cerebrovascular event.
10. Any known non-COVID-19, non-diabetes related, serious condition which, in the opinion of the clinical team, makes the patient unsuitable for the trial.
11. Known history of drug or alcohol abuse within previous 12 months of screening.
12. Known history of HIV, hepatitis C or unresolved hepatitis B or severe liver disease.
13. Current or planned use of gemfibrozil or any other strong inhibitors of CYP2C8.
14. Current or previous participation in another clinical trial where the patient has received a dose of an Investigational Medicinal Product (IMP) containing small molecule treatment(s) within 30 days or 5 half-lives (whichever is longer) prior to enrolment into this study, or containing biological treatment(s) within 3 months prior to entry into this study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St George Street Capital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kieran McCafferty, MD

Role: PRINCIPAL_INVESTIGATOR

Barts & The London NHS Trust

Locations

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Masarykova Univerzita - Fakultni Nemocnice U SV Anny V Brne (308)

Brno, , Czechia

Site Status

Nemocnice Hořovice (309)

Hořovice, , Czechia

Site Status

Oblastni Nemocnice Kolín (306)

Kolín, , Czechia

Site Status

Klaudianova Nemonice (302)

Mladá Boleslav, , Czechia

Site Status

Fakultni Nemocnice V Motole (303)

Prague, , Czechia

Site Status

Thomayerova Nemonice (310)

Prague, , Czechia

Site Status

Nemocnice Třebíč (305)

Třebíč, , Czechia

Site Status

Colentina Clinical Hospital (204)

Bucharest, , Romania

Site Status

Spitalul Clinic de Boli Infectioase Cluj-Napoca (203)

Cluj-Napoca, , Romania

Site Status

Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca (202)

Cluj-Napoca, , Romania

Site Status

Spitalul Clinic de Boli Infectioase Constanţa (207)

Constanța, , Romania

Site Status

Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Craiova (206)

Craiova, , Romania

Site Status

Spitalul Judetean de Urgenta Deva (208)

Deva, , Romania

Site Status

Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iaşi (205)

Iași, , Romania

Site Status

Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Timişoara (201)

Timișoara, , Romania

Site Status

Barnsley Hospital NHS Foundation Trust (105)

Barnsley, , United Kingdom

Site Status

Bolton NHS Foundation Trust (122)

Bolton, , United Kingdom

Site Status

Bradford Teaching Hospitals NHS Foundation Trust (103)

Bradford, , United Kingdom

Site Status

North Bristol NHS Trust (116)

Bristol, , United Kingdom

Site Status

County Durham and Darlington NHS Foundation Trust (121)

Darlington, , United Kingdom

Site Status

The Dudley Group NHS Foundation Trust (107)

Dudley, , United Kingdom

Site Status

Medway NHS Foundation Trust (108)

Gillingham, , United Kingdom

Site Status

Hull & East Yorkshire NHS Trust (102)

Hull, , United Kingdom

Site Status

Barts Health NHS Trust (101 and 111)

London, , United Kingdom

Site Status

Royal Free London NHS Foundation Trust (119)

London, , United Kingdom

Site Status

St George's University Hospitals NHS Foundation Trust (114)

London, , United Kingdom

Site Status

Penine Acute Hospitals NHS Trust (106)

Salford, , United Kingdom

Site Status

Sheffield Hospitals NHS Foundation Trust (104)

Sheffield, , United Kingdom

Site Status

Somerset NHS Foundation Trust (109)

Taunton, , United Kingdom

Site Status

Walsall Healthcare NHS Trust (113)

Walsall, , United Kingdom

Site Status

Countries

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Czechia Romania United Kingdom

References

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Chorlton J, Hollowood Z, Dyer C, Lockhart D, Boekman P, McCafferty K, Coffey P, Marelli-Berg F, Martin J. A randomised, double-blind, placebo-controlled, multicentre clinical trial of AZD1656 in diabetic patients hospitalised with COVID-19: The ARCADIA Trial - implications for therapeutic immune modulation. EClinicalMedicine. 2022 Sep;51:101604. doi: 10.1016/j.eclinm.2022.101604. Epub 2022 Aug 18.

Reference Type DERIVED
PMID: 35996565 (View on PubMed)

McCafferty K, Hollowood Z, Allen M, Lockhart D, Chorlton J, Martin J. ARCADIA study protocol: a phase II, randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with diabetes hospitalised with suspected or confirmed COVID-19. BMJ Open. 2021 Dec 1;11(12):e049650. doi: 10.1136/bmjopen-2021-049650.

Reference Type DERIVED
PMID: 34853102 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2020-002211-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SGS.1656.201

Identifier Type: -

Identifier Source: org_study_id

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