Tafenoquine in Patients With Mild to Moderate COVID-19

• ClinicalTrials.gov Identifier: NCT04533347
• Recruitment Status: Completed
• First Posted: August 31, 2020
• Last Update Posted: January 17, 2023
• Sponsor: 60 Degrees Pharmaceuticals LLC
• Information provided by (Responsible Party): 60 Degrees Pharmaceuticals LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID 19 Disease	Drug: Tafenoquine Oral Tablet; Drug: Placebo	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 19, 2021
• Actual Primary Completion Date: June 30, 2022
• Actual Study Completion Date: June 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Tafenoquine; Tafenoquine two 100 mg oral tablets 1x/day on Days 1,2,3 and 10	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.; Other Names: ARAKODA™; KODATEF™
Placebo Comparator: Placebo; Placebo two tablets 1x/day on Days 1,2,3 and 10	Drug: Placebo; Patients will be randomized and will receive and self-administer 200 mg Tafenoquine or matching placebo on Days 1, 2, 3, and 10.

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with clinical recovery of COVID-19 symptoms on Day 14 [ Time Frame: Day 14 [± 1 day] ]

Secondary Outcome Measures :

1. Increases the proportion of patients with absence of clinical symptoms by individual symptom at Day 14 [ Time Frame: Day 14 [± 1 day] ]
2. Decreases the hospitalization rate due to COVID-19 by Day 14 [ Time Frame: Day 14 [± 1 day] ]
3. Decreases the number of medical follow-up visits by Day 14. [ Time Frame: Day 14 [± 1 day] ]

Other Outcome Measures:

1. Planned Interim Analysis and Data Monitoring [ Time Frame: 100 patients randomized ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

Deluxe Health Center LLC

Miami, Florida, United States, 33014

Hope Clinical Trials

Miami, Florida, United States, 33165

F&T Medical Research, Inc.

Miami, Florida, United States, 33184

Kendall South Medical Center, Inc.

Miami, Florida, United States, 33185

United States, Nebraska

Skyline Medical Center

Elkhorn, Nebraska, United States, 68022

United States, North Carolina

Burke Primary Care

Morgantown, North Carolina, United States, 28655

United States, South Carolina

AFC Urgent Care

Easley, South Carolina, United States, 29640

United States, Texas

Centex Studies

Brownsville, Texas, United States, 78526

Care United

Forney, Texas, United States, 75126

Clinical Trial Network

Houston, Texas, United States, 77074

Sponsors and Collaborators

60 Degrees Pharmaceuticals LLC

More Information

Publications of Results:

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 MD, Ruiz-Palacios GM, Benfield T, Fatkenheuer G, Kortepeter MG, Atmar RL, Creech CB, Lundgren J, Babiker AG, Pett S, Neaton JD, Burgess TH, Bonnett T, Green M, Makowski M, Osinusi A, Nayak S, Lane HC; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8.

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.

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.

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

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. 2005 Dec;79(23):14614-21. doi: 10.1128/JVI.79.23.14614-14621.2005.

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, Rajasingham R, Boulware DR. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial. Ann Intern Med. 2020 Oct 20;173(8):623-631. doi: 10.7326/M20-4207. Epub 2020 Jul 16. Erratum In: Ann Intern Med. 2021 Mar;174(3):435.

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.

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, Zhang Y, Cao L, Guo T, Wan Y, Qin H, Jiang Y, Jaki T, Hayden FG, Horby PW, Cao B, Wang C. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May 16;395(10236):1569-1578. doi: 10.1016/S0140-6736(20)31022-9. Epub 2020 Apr 29. Erratum In: Lancet. 2020 May 30;395(10238):1694.

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

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 outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3. Erratum In: Nature. 2020 Dec;588(7836):E6.

Other Publications:

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.

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.

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

• Responsible Party: 60 Degrees Pharmaceuticals LLC
• ClinicalTrials.gov Identifier: NCT04533347
• Other Study ID Numbers: TQ 2020_06
• First Posted: August 31, 2020
• Last Update Posted: January 17, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by 60 Degrees Pharmaceuticals LLC:

mild to moderate COVID 19 disease; SARS-CoV-2; infectious disease; severe acute respiratory syndrome coronavirus 2

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Tafenoquine; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents