Official Title
A Phase II, Randomised, Double-blind, Placebo-controlled Clinical Trial to Assess the Safety and Efficacy of AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19
Brief Summary

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

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.

Completed
COVID19

Drug: AZD1656

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

Other: Placebo

Matched placebo tablets

Eligibility Criteria

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.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Czechia
Romania
United Kingdom
Locations

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

Nemocnice Hořovice (309)
Hořovice, Czechia

Oblastni Nemocnice Kolín (306)
Kolín, Czechia

Klaudianova Nemonice (302)
Mladá Boleslav, Czechia

Fakultni Nemocnice V Motole (303)
Prague, Czechia

Thomayerova Nemonice (310)
Prague, Czechia

Nemocnice Třebíč (305)
Třebíč, Czechia

Colentina Clinical Hospital (204)
Bucharest, Romania

Spitalul Clinic de Boli Infectioase Cluj-Napoca (203)
Cluj-Napoca, Romania

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

Spitalul Clinic de Boli Infectioase Constanţa (207)
Constanţa, Romania

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

Spitalul Judetean de Urgenta Deva (208)
Deva, Romania

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

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

Barnsley Hospital NHS Foundation Trust (105)
Barnsley, United Kingdom

Bolton NHS Foundation Trust (122)
Bolton, United Kingdom

Bradford Teaching Hospitals NHS Foundation Trust (103)
Bradford, United Kingdom

North Bristol NHS Trust (116)
Bristol, United Kingdom

County Durham and Darlington NHS Foundation Trust (121)
Darlington, United Kingdom

The Dudley Group NHS Foundation Trust (107)
Dudley, United Kingdom

Medway NHS Foundation Trust (108)
Gillingham, United Kingdom

Hull & East Yorkshire NHS Trust (102)
Hull, United Kingdom

Barts Health NHS Trust (101 and 111)
London, United Kingdom

Royal Free London NHS Foundation Trust (119)
London, United Kingdom

St George's University Hospitals NHS Foundation Trust (114)
London, United Kingdom

Penine Acute Hospitals NHS Trust (106)
Salford, United Kingdom

Sheffield Hospitals NHS Foundation Trust (104)
Sheffield, United Kingdom

Somerset NHS Foundation Trust (109)
Taunton, United Kingdom

Walsall Healthcare NHS Trust (113)
Walsall, United Kingdom

Kieran McCafferty, MD, Principal Investigator
Barts & The London NHS Trust

St George Street Capital
NCT Number
Keywords
Covid-19
Diabetes Mellitus
SARS-CoV-2
Regulatory T Cell
Glucokinase
MeSH Terms
COVID-19