A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression

NCT05947812 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: TQ 2022-08
• Study Type: interventional
• Target: 148
• Locations: 0 countries
• Sites: N/A

Brief Summary

A clinical study to assess the efficacy and safety of oral tafenoquine compared to placebo in patients with mild to moderate COVID 19 disease and low risk of disease progression (the "ACLR8-LR" study).

Conditions

COVID 19 Disease; Mild to Moderate COVID 19 Disease; SARS-CoV-2; Infectious Disease; Severe Acute Respiratory Syndrome Coronavirus 2

Outcome Measures

Primary Outcomes (1)

• Time to sustained clinical recovery from COVID-19 symptoms (4 uninterrupted days of aggregate symptom scores ≤ 2) through Day 28 (± 2 days)

  Day 28 (± 2 days)

Secondary Outcomes (9)

• MCP-1 levels at Days 5, 14 (± 1 day) and 28 (± 2 days)

  Days 5, 14 (± 1 day) and 28 (± 2 days)

• Day 5 aggregate symptom score (FDA's 14 COVID-19 symptoms)

  Day 5

• Time to clinical resolution (uninterrupted daily aggregate symptom score ≤ 2 for at least 1, 2 or 3 occasions) of all COVID-19 symptoms through Day 28 (± 2 days)

  Day 28 (± 2 days)

• Time to sustained clinical resolution (uninterrupted daily aggregate symptom score ≤ 2 for at least 1, 2, 3, or 4 occasions) of all COVID-19 symptoms through Days 14 (± 1 day) and 42 (± 2 days)

  Days 14 (± 1 day) and 42 (± 2 days)

• Proportion of patients with sustained clinical resolution (uninterrupted daily aggregate symptom score ≤ 2 on at least 1, 2, or 3 or 4 occasions) of all COVID-19 symptoms at Days 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days)

  Days 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days)

Other Outcomes (11)

• Proportion of patients with negative COVID-19 rapid antigen test at Day 7 (± 1 day) and at first report after day 3 of feeling able to resume normal activities (± 1 days)

  Day 7 (± 1 day) and at first report after day 3 of feeling able to resume normal activities (± 1 days)

• Clinical relapse through Day 42 (± 2 days) of COVID symptoms defined as at least three days of aggregate symptoms score > 2 after achieving clinical recovery for the primary endpoint

  Day 42 (± 2 days)

• Time to first report by the patient that they can resume normal activities

  Time to first report by the patient

Study Arms (2)

Tafenoquine

EXPERIMENTAL

Tafenoquine two tablets 1x/day on Days 1, 2, 3, and then weekly (Days 10 ± 1 day, 17 ± 2 days, 24 ± 2 days, 31 ± 2 days and 38 ± 2 days) until sustained clinical recovery

Drug: Tafenoquine Oral Tablet

Placebo

PLACEBO COMPARATOR

Placebo two tablets 1x/day on Days 1, 2, 3, and then weekly (Days 10 ± 1 day, 17 ± 2 days, 24 ± 2 days, 31 ± 2 days and 38 ± 2 days) until sustained clinical recovery

Drug: Placebo

Interventions

Tafenoquine Oral Tablet DRUG

Patients will be randomized and will receive and self-administer 200 mg Tafenoquine on Days 1, 2, 3, and then weekly (Days 10 ± 1 day, 17 ± 2 days, 24 ± 2 days, 31 ± 2 days and 38 ± 2 days) until sustained clinical recovery.

Also known as: KODATEF™, Arakoda

Tafenoquine

Placebo DRUG

Patients will be randomized and will receive and self-administer 200 mg Tafenoquine or matching placebo on Days 1, 2, 3, and then weekly (Days 10 ± 1 day, 17 ± 2 days, 24 ± 2 days, 31 ± 2 days and 38 ± 2 days) until sustained clinical recovery.

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female, aged ≥18, regardless of COVID-19 vaccination status;
• Laboratory confirmed infection COVID-19 disease as determined using an FDA-authorized COVID-19 rapid antigen test;
• Able and willing to give written informed consent;
• Willing to complete the following study activities and assessments:
• Keep an electronic diary from Study Days 2 through 42.
• Have phone or videoconferences with study team personnel on Study Days 10, 21, and 35.
• Have study samples collected in-home on Days 5, 14, 28, and 42
• Agree to return to clinic for additional safety evaluations if needed, as determined by the study team;
• An aggregate patient-reported COVID-19 symptom score of at ≥3 on the first day of drug administration (Study Day 1).
• Must agree not to enroll in another study of an investigational agent prior to completion of Day 42 of the study;
• Able to take ARAKODA according to Prescribing Information
• Have been symptomatic no longer than 7 days inclusive of Day 1 when the first dose of study medication is administered.
• If female, agree to use an acceptable method of birth control from the time of consent through 56 days after the last dose of study drug.
• Possess a smart phone or tablet, or are willing to utilize a sponsor-provided device if available.

You may not qualify if:

• Have any of the contraindications for ARAKODA in the prescribing information including:
• G6PD deficiency
• Breastfeeding
• Psychotic disorder or current psychotic symptoms
• Known hypersensitivity reaction to TQ
• Evidence of severe or critical illness, defined by at least one of the following:
• Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory rate ≥30 breaths per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air
• Respiratory failure defined based on resource utilization requiring at least one of the following: i. Endotracheal intubation and mechanical ventilation, oxygen delivered by high flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO), or clinical diagnosis of respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation); ii. Shock (defined by systolic blood pressure \<90 mmHg, or diastolic blood pressure \<60 mmHg or requiring vasopressors); iii. Multi-organ dysfunction/failure
• Any other clinically significant acute illness unrelated to COVID-19 within seven days prior to first study drug administration;
• Receipt of any approved or experimental small molecule treatment for COVID-19 (FDA-approved, off-label, compassionate use, or study-related) within the 30 days prior to the time of the screening evaluation
• Receipt of any approved or experimental biologic therapeutic for COVID-19 (FDA-approved, off-label, compassionate use, or study-related) within the 90 days prior to the time of the screening evaluation
• Have been diagnosed (and confirmed by PCR or rapid antigen test) with COVID-19 in the 90 days prior to randomization (other than for this infection);
• Any COVID-19 symptoms which, in the opinion of the investigator, is suggestive of possible requirement to hospitalize within 48 hours of enrollment.
• Positive pregnancy test;
• Are ≥65 years of age and have a clinical frailty score \> 5;

Sponsors & Collaborators

• 60P Australia Pty Ltd: lead

Related Publications (11)

• 60º Pharmaceuticals LLC. Clinical Study Report, TQ 2020_06. A double-blind placebo-controlled study to assess the efficacy and safety of oral tafenoquine versus placebo in patients with mild to moderate COVID-19 disease. 14 July 2022

  RESULT

• Bobrowski T, Chen L, Eastman RT, Itkin Z, Shinn P, Chen CZ, Guo H, Zheng W, Michael S, Simeonov A, Hall MD, Zakharov AV, Muratov EN. Synergistic and Antagonistic Drug Combinations against SARS-CoV-2. Mol Ther. 2021 Feb 3;29(2):873-885. doi: 10.1016/j.ymthe.2020.12.016. Epub 2020 Dec 15.

  PMID: 33333292 RESULT

• Brueckner RP, Lasseter KC, Lin ET, Schuster BG. First-time-in-humans safety and pharmacokinetics of WR 238605, a new antimalarial. Am J Trop Med Hyg. 1998 May;58(5):645-9. doi: 10.4269/ajtmh.1998.58.645.

  PMID: 9598455 RESULT

• Chen Y, Yang WH, Chen HF, Huang LM, Gao JY, Lin CW, Wang YC, Yang CS, Liu YL, Hou MH, Tsai CL, Chou YZ, Huang BY, Hung CF, Hung YL, Wang WJ, Su WC, Kumar V, Wu YC, Chao SW, Chang CS, Chen JS, Chiang YP, Cho DY, Jeng LB, Tsai CH, Hung MC. Tafenoquine and its derivatives as inhibitors for the severe acute respiratory syndrome coronavirus 2. J Biol Chem. 2022 Mar;298(3):101658. doi: 10.1016/j.jbc.2022.101658. Epub 2022 Jan 29.

  PMID: 35101449 RESULT

• Dow GS, Luttick A, Fenner J, Wesche D, Yeo KR, Rayner C. Tafenoquine inhibits replication of SARS-CoV-2 at pharmacologically relevant cincentrations in vitro. Biorxiv; Tafenoquine inhibits replication of SARS-Cov-2 at pharmacologically relevant concentrations in vitro. bioRxiv.2020. https://doi.org/10.1101/2020.07.12.199059

  RESULT

• Dow GS, Smith BL. A phase II, double blind, placebo-controlled, randomized evaluation of the safety and efficacy of tafenoquine in patients with mild-moderate COVID-19 disease. New Microbes New Infect. 2022 Jun 1;47:100986. doi: 10.1016/j.nmni.2022.100986. eCollection 2022 Apr-May.

  PMID: 35668841 RESULT

• Grassin-Delyle S, Salvator H, Brollo M, Catherinot E, Sage E, Couderc LJ, Naline E, Devillier P. Chloroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants. Clin Infect Dis. 2020 Nov 19;71(16):2265-2268. doi: 10.1093/cid/ciaa546.

  PMID: 32382733 RESULT

• Sato R, Imaizumi T, Aizawa T, Watanabe S, Tsugawa K, Kawaguchi S, Seya K, Matsumiya T, Tanaka H. Inhibitory effect of anti-malarial agents on the expression of proinflammatory chemokines via Toll-like receptor 3 signaling in human glomerular endothelial cells. Ren Fail. 2021 Dec;43(1):643-650. doi: 10.1080/0886022X.2021.1908901.

  PMID: 33820486 RESULT

• Shivakumar S, Panigrahi T, Shetty R, Subramani M, Ghosh A, Jeyabalan N. Chloroquine Protects Human Corneal Epithelial Cells from Desiccation Stress Induced Inflammation without Altering the Autophagy Flux. Biomed Res Int. 2018 Nov 1;2018:7627329. doi: 10.1155/2018/7627329. eCollection 2018.

  PMID: 30519584 RESULT

• Song Y, Zhang H, Zhu Y, Zhao X, Lei Y, Zhou W, Yu J, Dong X, Wang X, Du M, Yan H. Lysozyme Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Inflammation in Human Corneal Epithelial Cells. Invest Ophthalmol Vis Sci. 2022 Jun 1;63(6):16. doi: 10.1167/iovs.63.6.16.

  PMID: 35713893 RESULT

• United States Centers for Disease Control. Daily update of COVID-19 cases. Accessed on 19 February 2023 at https://covid.cdc.gov/covid-data-tracker/#datatracker-home.

  RESULT

MeSH Terms

Conditions

Communicable Diseases

Interventions

tafenoquine

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Geoff Dow, PhD

CONTACT

202-327-5422; geoffdow@60degreespharma.com

Study Design

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

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: July 17, 2023
• Study Start: August 1, 2023
• Primary Completion: April 27, 2024
• Study Completion: April 27, 2024
• Last Updated: July 17, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share