Clinical Trial of Natural Therapeutics for COVID-19 and Other Acute Respiratory Viral Infections (CONAT)

Safety, Pharmacokinetics, and Preliminary Efficacy of Herbal Products for the Treatment of Acute Respiratory Viral Infections Including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Uganda; Phase 2A Open Label Clinical Trial

The trial "Safety, Pharmacokinetics and Preliminary Efficacy of herbal products for the treatment of acute respiratory viral infections including SARS-CoV2 in Uganda; Phase 2A Open Label Clinical Trial" is currently being implemented under the Clinical Trials of Natural therapeutics Program. The trial sample size is 510, and the participants include adults (18 years or more) who fulfill the case definitions of acute respiratory infections (ARI), test positive for one of the target respiratory viruses, are negative for TB on GeneXpert; non-pregnant/non-breast-feeding females, have no history of hypersensitivity to any of the investigational products, and have given written consent to participate in the trial.

The overall objective of the trial is to assess the safety, pharmacokinetics and preliminary efficacy of TazCoV and Vidicine for the treatment of acute respiratory viral infections including (SARS-CoV2, RSV and Influenza A/B) in Uganda.

Primary objectives include:

1. To determine the safety and pharmacokinetics of TAZCOV and Vidicine herbal products among adult participants patients with acute respiratory infections including those due to laboratory-confirmed SARS-CoV2, RSV and Influenza A/B
2. To determine the extent of SARS-CoV2, RSV, and Influenza A/B viral clearance among adult participants patients with acute viral respiratory infection treated using TAZCOV and Vidicine
3. To establish time-to-remission of symptoms among participants patients with acute respiratory infections including those due to laboratory-confirmed SARS-CoV2, RSV and Influenza treated with TAZCOV or Vidicine
4. To evaluate disease progression among participants patients with acute respiratory infections including those due to laboratory-confirmed SARS-CoV2, RSV and Influenza treated with TAZCOV or Vidicine The end points include: Solicited and unsolicited side effects (mild, moderate, severe, adverse and serious adverse events), days to viral clearance (RT-PCR negativity) for those with a positive viral test at enrolment and time to presenting symptom resolution. The Pharmacokinetic endpoints include: the maximum concentration of IMP in plasma [Cmax], time taken for the IMP plasma concentration to reach maximum levels [Tmax] and time taken for the concentration of the IMP in the plasma or the total amount in the body to be reduced by 50%.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Infection
• Intervention / Treatment: Drug: TAZCOV; Drug: Vidicine

• Study Type: Interventional
• Enrollment (Estimated): 510
• Phase: Phase 2

Contacts and Locations

Study Locations

• Uganda
  • Central
    • Kampala, Central, Uganda
      • Recruiting
      • Mulago National Referral Hospital
      • Contact: Bruce Kirenga, PhD; Phone Number: 256782404431; Email: brucekirenga@gmail.com
      • Contact: Winters Muttamba, MPH; Phone Number: 256772511261
      • Principal Investigator: Bruce Kirenga, PhD
      • Sub-Investigator: Pauline Byakika, PhD
      • Sub-Investigator: Noah Kiwanuka, PhD
      • Sub-Investigator: Jane Nakibuka, MMed
      • Sub-Investigator: Moses Ocan, MMed
      • Sub-Investigator: Winters Muttamba, MPH
      • Sub-Investigator: Darius Owachi, MMed
      • Sub-Investigator: Joseph Okia, MMed
      • Sub-Investigator: Moses Joloba, PhD
      • Sub-Investigator: Barnabas Bakamutumaho, PhD
      • Sub-Investigator: Jackline Kyosimire, MMed
      • Sub-Investigator: Edward Wampande, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria: ALl adults who

• fulfill ARI case definition
• have signs and symptoms of ARI
• test positive for one of the target respiratory viruses (SARS-CoV2, RSV, or Influenza A/B)
• do not have symptoms suggestive of Pulmonary TB i.e cough for more than 2 weeks, drenching night sweats, evening fevers and marked weight loss.
• can provide informed consent or have a surrogate or legally appointed representative to give consent

Exclusion Criteria:

• Severe acute respiratory illness (SARI)-defined as An acute respiratory illness with a history of fever or measured fever of ≥ 38 °C and cough and/or throat with onset within the past 10 days, requiring hospitalization or with SPO2≤92%
• History of hypersensitivity to the investigational product or components therein
• Conditions that may be regarded as contraindications to the investigational medicinal product include known allergic reactions and rashes to any herbal medicines and any untoward reactions to any herbal medications such as bleeding, headaches, high blood pressure, heart failure, seizures, agitation, etc.
• Severe organ impairment (liver, kidney, brain, heart)
• Inability to return for post-discharge follow-up
• Females who are pregnant or intend to become pregnant or are breastfeeding during the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Investigational Medicinal product A (IMP A) + Standard of Care (SoC); Participants in this arm will receive the both the Investigational medicinal product (IMP A) and the standard of care	Drug: TAZCOV; Herbal Syrup
Active Comparator: Investigational Medicinal product B (IMP B) + Standard of Care (SoC); Participants in this arm will receive the both the Investigational medicinal product (IMP B) and the standard of care	Drug: Vidicine; Herbal Syrup
Other: Standard of care (SoC); Participants in this arm will receive only the standard of care	Drug: TAZCOV; Herbal Syrup; Drug: Vidicine; Herbal Syrup

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited and unsolicited side effects (mild, moderate, severe, adverse and serious adverse events).	The outcome measures are cumulative incidences of solicited and unsolicited side effects (mild, moderate, severe adverse events) in the study arms	9 months
Time to presenting symptom resolution	Will be assessed by time trends in clinical remission of signs and symptoms in the trial arms	14 days
Days to viral clearance (RT-PCR negativity) for those with a positive viral test at enrolment	Will be assessed through ascertaining the proportion with negative PCR on days 3, 5 and 7	7 days
Progression to severe-critical ARI requiring hospitalization, oxygen therapy and/or mortality	To be measured by ascertaining the proportion progressing to severe ARI requiring hospitalization, oxygen therapy and/or mortality	14 days
Time taken for TazCoV and Vidicine plasma concentration to reach maximum levels [Tmax]	To be measured by time to maximum concentration of TazCoV and Vidicine plasma [Tmax]	14 days

Collaborators and Investigators

• Sponsor: Makerere University
• Collaborators: MRC/UVRI and LSHTM Uganda Research Unit; Makerere University Lung Institute; Directorate of Government Analytical Laboratories; Makerere University College of Veterinary Medicine, Animal Resources and Bio-security; Makerere University Biomedical Research Centre; Natural Chemotherapeutics Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2024

Study Registration Dates

• First Submitted: May 25, 2023
• First Submitted That Met QC Criteria: June 8, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Virus Diseases; Respiratory Tract Infections
• Other Study ID Numbers: CONAT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be shared with other researchers upon reasonable request through the sponsor
• IPD Sharing Time Frame: 2 years after trial end
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No