Back to resultsAZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19 (ARCADIA)
Primary Purpose
Covid19
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD1656
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring COVID-19, Diabetes Mellitus, SARS-CoV-2, Regulatory T Cell, Glucokinase
Eligibility Criteria
Inclusion Criteria:
- Male or Female.
- Aged 18 and older.
- Have either Type I or Type II Diabetes Mellitus.
- 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.
- Blood glucose level at or above 4 mmol/L.
- Able to take oral (tablet) formulation of medication.
- Patient is able to provide written informed consent prior to initiation of any study procedures.
Exclusion Criteria:
- 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.
- Patients admitted with primary suspected or proven Mycoplasma pneumoniae, Chlamydia pneumoniae and bacterial pneumonia, who acquired COVID-19 while hospitalized.
- Treatment with immunomodulators or anti-rejection drugs within the last 3 months.
- Pregnant or breast feeding.
- 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.
- Anticipated transfer to another hospital which is not a study site within 72 hours.
- Known sensitivity to any of the study medication/placebo excipients.
- Prior dosing with AZD1656 on a previous clinical trial.
- Patients admitted as a result of and receiving immediate treatment for an acute asthmatic attack, acute myocardial infarction, acute cerebrovascular event.
- 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.
- Known history of drug or alcohol abuse within previous 12 months of screening.
- Known history of HIV, hepatitis C or unresolved hepatitis B or severe liver disease.
- Current or planned use of gemfibrozil or any other strong inhibitors of CYP2C8.
- 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.
Sites / Locations
- Masarykova Univerzita - Fakultni Nemocnice U SV Anny V Brne (308)
- Nemocnice Hořovice (309)
- Oblastni Nemocnice Kolín (306)
- Klaudianova Nemonice (302)
- Fakultni Nemocnice V Motole (303)
- Thomayerova Nemonice (310)
- Nemocnice Třebíč (305)
- Colentina Clinical Hospital (204)
- Spitalul Clinic de Boli Infectioase Cluj-Napoca (203)
- Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca (202)
- Spitalul Clinic de Boli Infectioase Constanţa (207)
- Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Craiova (206)
- Spitalul Judetean de Urgenta Deva (208)
- Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iaşi (205)
- Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Timişoara (201)
- Barnsley Hospital NHS Foundation Trust (105)
- Bolton NHS Foundation Trust (122)
- Bradford Teaching Hospitals NHS Foundation Trust (103)
- North Bristol NHS Trust (116)
- County Durham and Darlington NHS Foundation Trust (121)
- The Dudley Group NHS Foundation Trust (107)
- Medway NHS Foundation Trust (108)
- Hull & East Yorkshire NHS Trust (102)
- Barts Health NHS Trust (101 and 111)
- Royal Free London NHS Foundation Trust (119)
- St George's University Hospitals NHS Foundation Trust (114)
- Penine Acute Hospitals NHS Trust (106)
- Sheffield Hospitals NHS Foundation Trust (104)
- Somerset NHS Foundation Trust (109)
- Walsall Healthcare NHS Trust (113)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZD1656 (plus Usual Hospital Care)
Matched Placebo (plus Usual Hospital Care)
Arm Description
50mg film-coated tablets at a dose of 100mg BID
Matched placebo tablets
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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
Occurrence of Adverse Events
Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo
Occurrence of Serious Adverse Events
Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo
Duration of Hospitalisation
Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo
Mortality Rate
Mortality rate in patients receiving AZD1656 compared with placebo.
Intubation/Mechanical Ventilation
Number of Patients Receiving Intubation/Mechanical Ventilation
Full Information
NCT ID
NCT04516759
First Posted
August 14, 2020
Last Updated
April 21, 2022
Sponsor
St George Street Capital
1. Study Identification
Unique Protocol Identification Number
NCT04516759
Brief Title
AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
August 12, 2020 (Actual)
Primary Completion Date
April 25, 2021 (Actual)
Study Completion Date
May 12, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St George Street Capital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
COVID-19, Diabetes Mellitus, SARS-CoV-2, Regulatory T Cell, Glucokinase
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
170 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD1656 (plus Usual Hospital Care)
Arm Type
Experimental
Arm Description
50mg film-coated tablets at a dose of 100mg BID
Arm Title
Matched Placebo (plus Usual Hospital Care)
Arm Type
Placebo Comparator
Arm Description
Matched placebo tablets
Intervention Type
Drug
Intervention Name(s)
AZD1656
Intervention Description
50mg film-coated tablets (at daily dose of 100mg BID)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Matched placebo tablets
Primary Outcome Measure Information:
Title
Clinical Improvement by Day 14
Description
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.
Time Frame
Day 1 to Day 14
Secondary Outcome Measure Information:
Title
Clinical Improvement at Day 7, 14 and 21
Description
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).
Time Frame
Day 1 to Day 21
Title
Glycaemic Control
Description
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
Time Frame
Day 1 to Day 21
Title
Occurrence of Adverse Events
Description
Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo
Time Frame
Day 1 to Day 28
Title
Occurrence of Serious Adverse Events
Description
Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo
Time Frame
Day 1 to Day 28
Title
Duration of Hospitalisation
Description
Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo
Time Frame
Day 1 to Day 21
Title
Mortality Rate
Description
Mortality rate in patients receiving AZD1656 compared with placebo.
Time Frame
Day 1 to Day 28
Title
Intubation/Mechanical Ventilation
Description
Number of Patients Receiving Intubation/Mechanical Ventilation
Time Frame
Day 1 to Day 21
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or Female.
Aged 18 and older.
Have either Type I or Type II Diabetes Mellitus.
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.
Blood glucose level at or above 4 mmol/L.
Able to take oral (tablet) formulation of medication.
Patient is able to provide written informed consent prior to initiation of any study procedures.
Exclusion Criteria:
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.
Patients admitted with primary suspected or proven Mycoplasma pneumoniae, Chlamydia pneumoniae and bacterial pneumonia, who acquired COVID-19 while hospitalized.
Treatment with immunomodulators or anti-rejection drugs within the last 3 months.
Pregnant or breast feeding.
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.
Anticipated transfer to another hospital which is not a study site within 72 hours.
Known sensitivity to any of the study medication/placebo excipients.
Prior dosing with AZD1656 on a previous clinical trial.
Patients admitted as a result of and receiving immediate treatment for an acute asthmatic attack, acute myocardial infarction, acute cerebrovascular event.
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.
Known history of drug or alcohol abuse within previous 12 months of screening.
Known history of HIV, hepatitis C or unresolved hepatitis B or severe liver disease.
Current or planned use of gemfibrozil or any other strong inhibitors of CYP2C8.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kieran McCafferty, MD
Organizational Affiliation
Barts & The London NHS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masarykova Univerzita - Fakultni Nemocnice U SV Anny V Brne (308)
City
Brno
Country
Czechia
Facility Name
Nemocnice Hořovice (309)
City
Hořovice
Country
Czechia
Facility Name
Oblastni Nemocnice Kolín (306)
City
Kolín
Country
Czechia
Facility Name
Klaudianova Nemonice (302)
City
Mladá Boleslav
Country
Czechia
Facility Name
Fakultni Nemocnice V Motole (303)
City
Prague
Country
Czechia
Facility Name
Thomayerova Nemonice (310)
City
Prague
Country
Czechia
Facility Name
Nemocnice Třebíč (305)
City
Třebíč
Country
Czechia
Facility Name
Colentina Clinical Hospital (204)
City
Bucharest
Country
Romania
Facility Name
Spitalul Clinic de Boli Infectioase Cluj-Napoca (203)
City
Cluj-Napoca
Country
Romania
Facility Name
Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca (202)
City
Cluj-Napoca
Country
Romania
Facility Name
Spitalul Clinic de Boli Infectioase Constanţa (207)
City
Constanţa
Country
Romania
Facility Name
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Craiova (206)
City
Craiova
Country
Romania
Facility Name
Spitalul Judetean de Urgenta Deva (208)
City
Deva
Country
Romania
Facility Name
Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iaşi (205)
City
Iaşi
Country
Romania
Facility Name
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Timişoara (201)
City
Timişoara
Country
Romania
Facility Name
Barnsley Hospital NHS Foundation Trust (105)
City
Barnsley
Country
United Kingdom
Facility Name
Bolton NHS Foundation Trust (122)
City
Bolton
Country
United Kingdom
Facility Name
Bradford Teaching Hospitals NHS Foundation Trust (103)
City
Bradford
ZIP/Postal Code
BD9 6RJ
Country
United Kingdom
Facility Name
North Bristol NHS Trust (116)
City
Bristol
ZIP/Postal Code
BS10 5NB
Country
United Kingdom
Facility Name
County Durham and Darlington NHS Foundation Trust (121)
City
Darlington
Country
United Kingdom
Facility Name
The Dudley Group NHS Foundation Trust (107)
City
Dudley
ZIP/Postal Code
DY1 2HQ
Country
United Kingdom
Facility Name
Medway NHS Foundation Trust (108)
City
Gillingham
ZIP/Postal Code
ME7 5NY
Country
United Kingdom
Facility Name
Hull & East Yorkshire NHS Trust (102)
City
Hull
Country
United Kingdom
Facility Name
Barts Health NHS Trust (101 and 111)
City
London
ZIP/Postal Code
E1 1FR
Country
United Kingdom
Facility Name
Royal Free London NHS Foundation Trust (119)
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
St George's University Hospitals NHS Foundation Trust (114)
City
London
Country
United Kingdom
Facility Name
Penine Acute Hospitals NHS Trust (106)
City
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom
Facility Name
Sheffield Hospitals NHS Foundation Trust (104)
City
Sheffield
ZIP/Postal Code
S10 2SB
Country
United Kingdom
Facility Name
Somerset NHS Foundation Trust (109)
City
Taunton
ZIP/Postal Code
TA1 5DA
Country
United Kingdom
Facility Name
Walsall Healthcare NHS Trust (113)
City
Walsall
ZIP/Postal Code
WS2 9PS
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to deidentified individual participant data (IDP) that underlie the published clinical trial results.
IPD Sharing Time Frame
Requests for access to the data will be accepted beginning 6 months after article publication and will continue to be accepted for up to 5 years after publication.
IPD Sharing Access Criteria
Researchers must submit a methodologically sound research proposal to St George Street using the contact details provided on our website. See link below.
IPD Sharing URL
http://www.sgscapital.org
Citations:
PubMed Identifier
35996565
Citation
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.
Results Reference
derived
PubMed Identifier
34853102
Citation
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.
Results Reference
derived
Links:
URL
http://www.sgscapital.org
Description
Link to St George Street Capital's website
Learn more about this trial
AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19
We'll reach out to this number within 24 hrs