Tafenoquine in Patients With Mild to Moderate COVID-19

COVID 19 Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04533347
• Other study ID #: TQ 2020_06
• Status: Completed
• Phase: Phase 2
• Start date: February 19, 2021
• Est. completion date: June 30, 2022

Study information

• Verified date: January 2023
• Source: 60 Degrees Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The TQ 2020_06 study is a double-blind placebo-controlled, Phase 2 clinical trial that plans to enroll approximately 275 patients with mild to moderate infection with COVID-19. Patients will undergo a brief screening period before being randomized to receive either self-administer 200 mg tafenoquine or matching placebo for 10 days. Following the treatment period, patients will have a follow up visit at study Day 28 (28 days after the first dose of study medication). The study's primary efficacy endpoint is proportion of patients with clinical recovery from COVID-19 symptoms on Day 14 in patients with mild to moderate COVID-19 disease compared with placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female, aged =18 years of age;

• Laboratory confirmed infection with COVID-19 virus by an FDA-authorized SARS-Cov-2 RT-PCR;

• Able and willing to give written informed consent.

• Willing to keep an electronic diary from Study Day 1 to Study Day 13 (± 1 day) and Study Day 15 (± 1 day) to Study Day 28 (± 1 day)

• Willing to have daily phone or videoconferences with study team personnel from Study Day 1 to Day 13 (± 1 day) and Day 28

• At least one of the following clinical symptoms of COVID-19 infection within the 4 days prior to and inclusive of the day of screening:

1. Respiratory rate = 24/min

2. New cough or shortness of breath that has presented within the last 4 days

3. Fever - temperature 37.7°C [oral or skin surface]

• Must agree not to enroll in another study of an investigational agent prior to completion of Day 28 of the study.

• Able to take ARAKODA or KODATEF according to Prescribing Information

• Have been symptomatic no longer than 7 days 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.

Exclusion Criteria:

• Have one of the contraindications for ARAKODA or KODATEF in the prescribing information (section 16.1) including:

1. G6PD deficiency

2. Breastfeeding

3. Psychotic disorder or current psychotic symptoms

4. Known hypersensitivity reaction to TQ

• Evidence of severe or critical illness, defined by at least one of the following:

1. 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

2. 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 experimental treatment for COVID-19 (off-label, compassionate use, or study-related) within the 30 days prior to the time of the screening evaluation

• Any excluded concomitant medication as described in the ARAKODA package insert [Section 16.1]. Receipt of a COVID-19 vaccine is not exclusionary.

• 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

• Have been symptomatic for more than seven days when the first dose would be administered

Related Conditions & MeSH terms

• COVID 19 Disease
• COVID-19

Intervention

Drug:
• Tafenoquine Oral Tablet
Patients will be randomized and will receive and self-administer 200 mg Tafenoquine or matching placebo on Days 1, 2, 3, and 10.
• Placebo
Patients will be randomized and will receive and self-administer 200 mg Tafenoquine or matching placebo on Days 1, 2, 3, and 10.

Locations

Country	Name	City	State
United States	Centex Studies	Brownsville	Texas
United States	AFC Urgent Care	Easley	South Carolina
United States	Skyline Medical Center	Elkhorn	Nebraska
United States	Care United	Forney	Texas
United States	Clinical Trial Network	Houston	Texas
United States	Deluxe Health Center LLC	Miami	Florida
United States	F&T Medical Research, Inc.	Miami	Florida
United States	Hope Clinical Trials	Miami	Florida
United States	Kendall South Medical Center, Inc.	Miami	Florida
United States	Burke Primary Care	Morgantown	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
60 Degrees Pharmaceuticals LLC

Country where clinical trial is conducted

United States, 

References & Publications (13)

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, Hohmann E, Chu HY, Luetkemeyer A, Kline S, Lopez de Castilla D, Finberg RW, Dierberg K, Tapson V, Hsieh L, Patterson TF, Paredes R, Sweeney DA, Short WR, Touloumi G, Lye DC, Ohmagari N, Oh M — View Citation

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. — View Citation

Center for Disease Control. CDC Covid-19 data tracker. https://www.cdc.gov/covid-data-tracker/index.html#cases. Accessed March 7, 2020.

Crisafulli E, Clini EM. Measures of dyspnea in pulmonary rehabilitation. Multidiscip Respir Med. 2010 Jun 30;5(3):202-10. doi: 10.1186/2049-6958-5-3-202. — View Citation

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

Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, Labella A, Manson DK, Kubin C, Barr RG, Sobieszczyk ME, Schluger NW. Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020 Jun 18;382(25):2411-2418. doi: 10.1056/NEJMoa2012410. Epub 2020 May 7. — View Citation

Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, Farzan M, Wohlford-Lenane C, Perlman S, McCray PB Jr. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol. 2 — View Citation

Skipper CP, Pastick KA, Engen NW, Bangdiwala AS, Abassi M, Lofgren SM, Williams DA, Okafor EC, Pullen MF, Nicol MR, Nascene AA, Hullsiek KH, Cheng MP, Luke D, Lother SA, MacKenzie LJ, Drobot G, Kelly LE, Schwartz IS, Zarychanski R, McDonald EG, Lee TC, Ra — View Citation

Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health. 2020 Mar;25(3):278-280. doi: 10.1111/tmi.13383. Epub 2020 Feb 16. No abstract available. — View Citation

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, Fu S, Gao L, Cheng Z, Lu Q, Hu Y, Luo G, Wang K, Lu Y, Li H, Wang S, Ruan S, Yang C, Mei C, Wang Y, Ding D, Wu F, Tang X, Ye X, Ye Y, Liu B, Yang J, Yin W, Wang A, Fan G, Zhou F, Liu Z, Gu X, Xu J, Shang L, Zhan — View Citation

Worldometer. Coronavirus Update (Live). https://www.worldometers.info/coronavirus/. Accessed March 7, 2020.

Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology. 2020 May;158(6):1831-1833.e3. doi: 10.1053/j.gastro.2020.02.055. Epub 2020 Mar 3. No abstract available. — View Citation

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outb — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Planned Interim Analysis and Data Monitoring	Binding futility analysis of primary endpoint will be performed a minimum of 3 weeks after the earlier of [i] 100 pts. randomized or [ii] 6 months has elapsed since randomization of the first pt. in the study. Objective is to determine if tafenoquine increases the proportion of pts. with clinical recovery from COVID-19 symptoms on Day 14 in pts. with mild/moderate COVID-19 disease compared with placebo. Enrolment may be paused by sponsor prior to futility analysis if total number of pts. randomized reaches n=100 and re-initiated by sponsor after completion of futility analysis, if continuing study is determined to be non-futile. Unblinded interim analysis will be conducted by DMC statistician and results will be presented to DMC. If conditional power is less than the predetermined threshold, DMC will recommend terminating enrollment. Sponsor and study team will remain blinded, but will curtail enrollment based on recommendation of the DMC.	100 patients randomized
Primary	Proportion of patients with clinical recovery of COVID-19 symptoms on Day 14		Day 14 [± 1 day]
Secondary	Increases the proportion of patients with absence of clinical symptoms by individual symptom at Day 14		Day 14 [± 1 day]
Secondary	Decreases the hospitalization rate due to COVID-19 by Day 14		Day 14 [± 1 day]
Secondary	Decreases the number of medical follow-up visits by Day 14.		Day 14 [± 1 day]