Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19 (CLARITY 2)

• ClinicalTrials.gov Identifier: NCT05122182
• Recruitment Status: Recruiting
• First Posted: November 16, 2021
• Last Update Posted: March 29, 2022
• Sponsor: University of Sydney
• Collaborator: The George Institute for Global Health, India
• Information provided by (Responsible Party): University of Sydney

Tracking Information

• First Submitted Date: November 14, 2021
• First Posted Date: November 16, 2021
• Last Update Posted Date: March 29, 2022
• Actual Study Start Date: January 7, 2022
• Estimated Primary Completion Date: July 14, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2021)

Clinical Health Score at day 14 [ Time Frame: 14 days ]

The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 14, which is determined within an 8-point ordinal scale of health status:

1. Not hospitalised, no limitations on activities.
2. Not hospitalised, limitation on activities.
3. Hospitalised, not requiring supplemental oxygen.
4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
6. Hospitalised, requiring intubation and mechanical ventilation.
7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
8. Death.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 14, 2021)

• Clinical Health Score at day 28 [ Time Frame: 28 days ]
  The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 28, which is determined within an 8-point ordinal scale of health status:

  1. Not hospitalised, no limitations on activities.
  2. Not hospitalised, limitation on activities.
  3. Hospitalised, not requiring supplemental oxygen.
  4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
  5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
  6. Hospitalised, requiring intubation and mechanical ventilation.
  7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
  8. Death.
• ICU admission [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of ICU admission in days 0-28.
• Death [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of deaths in days 0-28.
• Time to death [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed from hospital admission to death.
• Acute Kidney Injury [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of acute kidney injury in days 0-28.
• Respiratory Failure [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of respiratory failure in days 0-28.
• Length of hospital admission [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by days of inpatient stay from admission to discharge or death.
• Length of ICU Admission [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by days in ICU from admission to transfer to ward or death.
• Requirement of ventilatory support [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by count of days with ventilation in days 0-28.
• Requirement of dialysis [ Time Frame: 28 days ]
  The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by count of days with dialysis in days 0-28.
• Clinical Health Score at day 60 [ Time Frame: 60 days ]
  The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 60, which is determined within an 8-point ordinal scale of health status:

  1. Not hospitalised, no limitations on activities.
  2. Not hospitalised, limitation on activities.
  3. Hospitalised, not requiring supplemental oxygen.
  4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
  5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
  6. Hospitalised, requiring intubation and mechanical ventilation.
  7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
  8. Death.
• Clinical Health Score at day 90 [ Time Frame: 90 days ]
  The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 90, which is determined within an 8-point ordinal scale of health status:

  1. Not hospitalised, no limitations on activities.
  2. Not hospitalised, limitation on activities.
  3. Hospitalised, not requiring supplemental oxygen.
  4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
  5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
  6. Hospitalised, requiring intubation and mechanical ventilation.
  7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
  8. Death.
• Clinical Health Score at day 180 [ Time Frame: 180 days ]
  The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 180, which is determined within an 8-point ordinal scale of health status:

  1. Not hospitalised, no limitations on activities.
  2. Not hospitalised, limitation on activities.
  3. Hospitalised, not requiring supplemental oxygen.
  4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
  5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
  6. Hospitalised, requiring intubation and mechanical ventilation.
  7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
  8. Death.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: November 14, 2021)

• Incidence of Hypotension [ Time Frame: 28 days ]
  The specific safety objectives are to evaluate the safety of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of hypotension in days 0-28.
• Incidence of Hyperkalemia [ Time Frame: 28 days ]
  The specific safety objectives are to evaluate the safety of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of hyperkalemia in days 0-28.
• Incidence of Deranged Liver Function Tests [ Time Frame: 28 days ]
  The specific safety objectives are to evaluate the safety of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of deranged liver function tests in days 0-28.
• Total Serious Adverse Events (SAEs) [ Time Frame: 28 days ]
  The specific safety objectives are to evaluate the safety of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by total number of SAEs in days 0-28.
• Incidence of hospital readmission [ Time Frame: 90 days ]
  Admission for overnight stay up to day 90 following initial hospital discharge.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19
• Official Title: An Investigator Initiated, International Multi-Centre, Multi-Arm, Multi-Stage Randomised Double Blind Placebo Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19
• Brief Summary: CLARITY 2.0 is an investigator-initiated trial that will evaluate the safety and efficacy of dual treatment with repagermanium, a CCR2 antagonist, and candesartan, an ARB, in patients hospitalised with COVID-19 disease.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• COVID-19
• SARS-CoV2 Infection

Intervention

• Drug: Candesartan Cilexetil
  Angiotensin Receptor Blocker (ARB)
• Drug: Repagermanium
  C-C chemokine receptor type 2 (CCR2) antagonist
  Other Name: DMX-200
• Drug: Candesartan Placebo
  Angiotensin Receptor Blocker (ARB) placebo
• Drug: Repagermanium Placebo
  C-C chemokine receptor type 2 (CCR2) antagonist placebo

Study Arms

• Experimental: Interventional Arm
  Titratable candesartan with commencing dose 4mg tablets twice daily (daily dose 8 mg) + fixed dose repagermanium one x 120mg immediate release capsule twice daily (total daily dose 240mg). Treatment will continue for 28 days.
  Interventions:

  • Drug: Candesartan Cilexetil
  • Drug: Repagermanium
• Placebo Comparator: Control Arm #1
  Titratable candesartan with commencing dose 4mg tablets twice daily (daily dose 8 mg) + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days.
  Interventions:

  • Drug: Candesartan Cilexetil
  • Drug: Repagermanium Placebo
• Placebo Comparator: Control Arm #2
  Titratable matched placebo candesartan one tablet twice daily + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days.
  Interventions:

  • Drug: Candesartan Placebo
  • Drug: Repagermanium Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2021): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 29, 2022
• Estimated Primary Completion Date: July 14, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adults aged ≥ 18 years (maximum 65 years old in India).
2. Laboratory-confirmed diagnosis of SARS-CoV-2 infection within 10 days prior to randomisation. (Confirmation must be through Reverse Transcription Polymerase Chain Reaction [RT-PCR] method)
3. Intended for hospital admission for management of COVID-19.
4. Patients with moderate (respiratory rate of ≥ 24/minute or SPO2: 90% to ≤ 93% on room air) or severe (respiratory rate of ≥ 30/minute or SPO2: <90% on room air) COVID-19.
5. Systolic Blood Pressure (SBP) ≥ 120 mmHg OR SBP ≥ 115 mmHg and currently treated with a non-RAASi BP lowering agent that can be ceased.
6. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
7. Documented informed consent.

Exclusion Criteria:

1. Currently treated with an ACEi, ARB or aldosterone antagonist, aliskiren, or ARNi
2. Intolerance of ARBs
3. Serum potassium >5.5 mmol/L
4. An estimated Glomerular Filtration Rate (eGFR) <30ml/min/1.732m
5. Known biliary obstruction, known severe hepatic impairment (Child-Pugh-Turcotte score 10-15)
6. Pregnancy, lactation, or inadequate contraception.
7. Participation in a study of a novel investigational product within 28 days prior to randomisation.
8. Plans to participate in another study of a novel investigational product during this study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Katrina Diamante; +612 9562 5000; Clarity2.study@sydney.edu.au

• Listed Location Countries: India

Administrative Information

• NCT Number: NCT05122182
• Other Study ID Numbers: CTC0312
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Sydney
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Sydney
• Original Study Sponsor: Same as current
• Collaborators: The George Institute for Global Health, India

Investigators

• Study Chair: Meg Jardine; NHMRC Clinical Trials Centre, The University of Sydney
• Study Chair: Vivekanand Jha; The George Institute for Global Health, India

• PRS Account: University of Sydney
• Verification Date: March 2022