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 (CLARITY 2.0)

 

Background:

A partner to the CLARITY trial, CLARITY 2.0 will assess the use of a combination therapy – an ARB plus a CCR2 antagonist for the limitation and reduction of severity of COVID-19.

Repagermanium is a CCR2 antagonist, with an established safety profile and few adverse events. ARBs are widely used medications with a robust safety profile. When administered concurrently with an ARB, the CCR2 antagonist, repagermanium, is designed to inhibit recruitment of monocytes via both the AT1R and CCR2 pathways implicated in the inflammatory environment of the lungs of people affected by COVID-19.

Repagermanium is currently being tested in one other study in the setting of COVID-19 (REMAP-CAP).

 

Research Methodology:

The CLARITY 2.0 trial is an investigator-initiated, phase III, multicentre, international, prospective, randomised controlled trial.

Participants will be randomised to either:

  • Experimental intervention: Standard Care + Candesartan + Repagermanium
  • Control #1: Standard Care + Candesartan + Placebo (Repagermanium)
  • Control #2: Standard Care + Placebo (Candesartan) + Placebo (Repagermanium)

CLARITY 2.0 will recruit 600 participants within stage 1 of the trial. An interim analysis will be performed following recruitment to stage 1, which will inform continued recruitment of the full phase 3 trial. The trial will utilise adaptive sample size re-estimation methodology whereby recruitment of participants will continue until prespecified statistical rules are met. Participants will be recruited from India.

 

Aim:

CLARITY 2.0 aims to evaluate the safety and efficacy of dual treatment with Repagermanium and Candesartan compared to placebo as treatment for patients hospitalised for management of COVID-19.

Supported By:

Dimerix Limited Academic Research Grant

Eligibility:

Potential participants must satisfy all of the following:

  1. Adults aged ≥ 18 years
  2. Laboratory-confirmed diagnosis of SARS-CoV-2 infection within 10 days prior to randomisation.
  3. Intended for hospital admission for management of COVID-19.
  4. Systolic Blood Pressure (SBP) ≥ 120 mmHg OR SBP ≥ 115 mmHg and currently treated with a non-RAASi BP lowering agent that can be ceased.
  5. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
  6. Documented informed consent

Potential participants must NOT satisfy any of the following:

  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.
    1. Female participants must be either post-menopausal, infertile or use a reliable means of contraception for at least 60 days after the last dose of investigational product or refrain. Where they are of childbearing potential, female participants must also have a negative pregnancy test result within 7 days prior to registration.
    2. Male participants must have been surgically sterilised or use a (double if required) barrier method of contraception during the treatment period and for at least 60 days after the last dose of investigational product or refrain from donating sperm during this period.
  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.

Registration ID:

TBA

Participation:

India

Australian Lead Group:

NHMRC CTC

Status:

Start-up

Activation Date:

TBC

Chair:

Professor Meg Jardine

Contact:

Clarity2.study@sydney.edu.au

Publications:

Nil