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

Covid19 Clinical Trial

— ARCADIA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04516759
• Other study ID #: SGS.1656.201
• Secondary ID: 2020-002211-21
• Status: Completed
• Phase: Phase 2
• Start date: August 12, 2020
• Est. completion date: May 12, 2021

Study information

• Verified date: April 2022
• Source: St George Street Capital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: May 12, 2021
• Est. primary completion date: April 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Drug:
• AZD1656
50mg film-coated tablets (at daily dose of 100mg BID)

Other:
• Placebo
Matched placebo tablets

Locations

Country	Name	City	State
Czechia	Masarykova Univerzita - Fakultni Nemocnice U SV Anny V Brne (308)	Brno
Czechia	Nemocnice Horovice (309)	Horovice
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 Trebíc (305)	Trebíc
Romania	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 Constanta (207)	Constanta
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" Iasi (205)	Iasi
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Timisoara (201)	Timisoara
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
St George Street Capital

Countries where clinical trial is conducted

Czechia,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Improvement by Day 14	The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 14 versus baseline, comparing AZD1656 treatment with placebo. The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient.; Results are presented as number of responders. Patients who were assigned a WHO score of 1, 2 or 3 at Day 14 were considered a treatment responder. A patient who was discharged before Day 14 was also considered a responder. All other patients (WHO scores 4-8 at Day 14) were considered treatment failures.	Day 1 to Day 14
Secondary	Clinical Improvement at Day 7, 14 and 21	The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 7, Day 14 and Day 21 versus baseline, comparing AZD1656 treatment with placebo.; Results are presented as the percentage of patients categorised at each severity rating at each timepoint on the WHO 8-point OSCI scale.; The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient.; Study Drug Discontinuation was the date on which a patient discontinued treatment. Treatment was given for a maximum of 21 days, or until date of hospital discharge (WHO score 1 or 2), or date mechanical ventilation was required (WHO score 6 or 7) or until date of death (WHO score 8).	Day 1 to Day 21
Secondary	Glycaemic Control	Degree of glycaemic control as measured by the need to increase baseline medication requirements or the need to add additional diabetic medications to maintain appropriate blood glucose levels in patients receiving AZD1656 compared with placebo	Day 1 to Day 21
Secondary	Occurrence of Adverse Events	Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo	Day 1 to Day 28
Secondary	Occurrence of Serious Adverse Events	Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo	Day 1 to Day 28
Secondary	Duration of Hospitalisation	Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo	Day 1 to Day 21
Secondary	Mortality Rate	Mortality rate in patients receiving AZD1656 compared with placebo.	Day 1 to Day 28
Secondary	Intubation/Mechanical Ventilation	Number of Patients Receiving Intubation/Mechanical Ventilation	Day 1 to Day 21

External Links

•   Link to St George Street Capital's website