PHRU CoV01 A Trial of Triazavirin (TZV) for the Treatment of Mild-moderate COVID-19

NCT04581915 | Terminated Phase 2 DMC

• 1 other identifier: PHRU CoV01
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

A) Phase II: Early viral responses to triazavirin In hospitalised patients with mild-moderate COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days, the slope of increase of the Ct values of serial nasopharyngeal swabs to 12 days after initiation of treatment will be ≥24% higher than in hospitalised patients receiving standard of care treatment only. B) Phase III: Efficacy of triazavirin to improve clinical outcomes In hospitalised patients with mild-moderate laboratory proven COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days will reduce a composite outcome - death; ICU admission or mechanical ventilation; or prolonged duration of admission- by ≥29% when compared to the composite outcome in hospitalised patients receiving standard of care therapy only.

Conditions

Covid19

Keywords

SARS CoV2; Triazavirin; Novel anti-viral agent

Outcome Measures

Primary Outcomes (4)

• To compare the slope of cycle threshold(Ct) values of nasopharyngeal swabs in people receiving Triazavirin versus placebo

  To ascertain that indeed there is a biological effect of Triazavirin, we will compare slope of cycle threshold (Ct) values of nasopharyngeal swabs taken from all patients in the Phase II part of the trial. We require at least a 24% difference in slope.

  11 days per patient

• To assess the proportion of patients who progress to severe COVID-19 and the proportion who need ICU or die.

  We have selected a composite measure including three adverse outcomes, all of which have serious implications for the patient and the health system. We will combine: deaths; ICU admissions or mechanical ventilation; and prolonged hospital stays -defined in this study as \>14 days.

  1 month per patient

• To determine the proportion of patients who develop grade 3 or grade 4 adverse events on treatment

  We will compare rates of grade 3 and worse adverse events that occur whilst on treatment, and for up to 30 days after randomisation. We will also report on tolerability, by comparing the proportions by arm of those who had placebo/Triazavirin withheld permanently.

  1 month per patient

• To determine the proportion of patients who stop taking either placebo/Triazavirin

  We will report on tolerability by comparing the proportions by arm who had placebo/Triazavirin withheld permanently.

  1 month per patient

Study Arms (2)

Interventional

EXPERIMENTAL

Participants to receive Triazavirin 250mg po 8 hourly for 5 days

Drug: Triazavirin (Riamilovir)

Control

PLACEBO COMPARATOR

Participants to receive placebo po 8 hourly for 5 days

Other: Placebo

Interventions

Triazavirin (Riamilovir) DRUG

Capsule - 250mg 8 hourly po

Interventional

Placebo OTHER

Placebo capsule

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥18 years of age, who have a clinical presentation suggestive of COVID-19, or who have had a molecular laboratory assay that confirms SARS-CoV-2 infection that was collected prior to the first dose of study treatment.
• Patients with mild to moderate COVID-19 who need admission and may require oxygen at admission but not yet requiring escalation of oxygen therapy to CPAP, high flow nasal oxygen or intubation. We will not include patients with laboratory confirmation of SARS-CoV-2 who report no symptoms at all.
• Able to provide own consent
• Willing to have HIV test - unless already has clinical documentation of HIV infection (as evidenced by a HIV rapid test result during the admission, or any one of the following: a positive HIV ELISA assay; an ART prescription; a pill container for ART with the patient's name; a hard copy or an electronic viral load result that includes the patient's name showing detectable HIV copies; clinical documentation of HIV sero-positivity included in the medical record)
• Randomisation must occur within 48 hours of first COVID-19 diagnosis during the current illness.

You may not qualify if:

• Women who are pregnant or breastfeeding at the time of enrolment
• Weight \<40kg.
• Evidence of current liver disease (AST/ALT \>3x ULN ; total bilirubin\>3xULN or prior history of cirrhosis or other chronic liver disease)
• Renal dysfunction as evidenced by an estimated glomerular filtration rate (eGFR) \<60ml/min, or prior/current diagnosis of chronic kidney disease.
• Prior receipt of any treatment with putative or proven anti-SARS-Cov-2 activity apart from the following: chloroquine, hydroxychloroquine, or ritonavir/lopinavir initiated no more than 12 hours prior to first receipt of TZV/placebo for this trial. Antiretrovirals initiated prior to admission as treatment for HIV, supportive, steroidal and non-steroidal anti-inflammatory, or anti-pyretic treatments are allowed.
• Indication for immediate initiation of antiretroviral therapy in HIV-infected patients, who are unable to delay ART initiation or re-initiation until the treatment phase of this study is complete.
• Permanently lives or works more than 120km from the hospital where recruited
• Unable to provide own consent
• In the opinion of either the attending doctor, or a study investigator that the patient is not a candidate for a clinical trial
• Receipt of anti-epileptic medication, warfarin or TB treatment at the time of recruitment or during the receipt of trial treatment.
• Enrolled currently in a trial of novel preventive treatment or treatment of SARS-CoV-2.
• Potential participants who are investigational site staff members, or relatives of a site staff member, or those who are employees of PharmaCentrix involved in the conduct of the trial.

Sponsors & Collaborators

• Wits Health Consortium (Pty) Ltd: lead
• PharmaCentrix (Pty) Ltd: collaborator
• Perinatal HIV Research Unit of the University of the Witswatersrand: collaborator

Study Sites (1)

The Perinatal HIV Research Unit - Matlosana

Klerksdorp, North West, South Africa

Location

MeSH Terms

Conditions

COVID-19

Interventions

riamilovir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Neil A Martinson, MBChB

  Perinatl HIV Research Unit CEO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Pharmacists
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are assigned to an interventional group or a placebo group after randomisation in parallel for the duration of the study.

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: October 9, 2020
• Study Start: September 8, 2020
• Primary Completion: April 20, 2021
• Study Completion: April 20, 2021
• Last Updated: August 2, 2022

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)