COVID 19 Disease, Infectious Disease, Mild to Moderate COVID 19 Disease, SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2
Conditions
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).
Detailed description
The TQ 2020\_08 study is a double-blind placebo-controlled, Phase 2b clinical trial that plans to enroll approximately 148 non-hospitalized patients with mild to moderate COVID 19 disease and low risk of disease progression (the ACLR8-LR study). Patients will undergo a brief screening period before being randomized to receive either self-administered 200 mg tafenoquine or matching placebo for up to 38 days. Following the treatment period, patients will have a follow up visit at study Day 42. The study's primary efficacy endpoint is time to sustained clinical recovery from COVID-19 symptoms (4 uninterrupted days of aggregate symptom scores ≤ 2) through Day 28 (± 2 days).
Interventions
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.
DRUGPlacebo
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.
Sponsors
60P Australia Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, aged ≥18, regardless of COVID-19 vaccination status; 2. Laboratory confirmed infection COVID-19 disease as determined using an FDA-authorized COVID-19 rapid antigen test; 3. Able and willing to give written informed consent; 4. Willing to complete the following study activities and assessments: 1. Keep an electronic diary from Study Days 2 through 42. 2. Have phone or videoconferences with study team personnel on Study Days 10, 21, and 35. 3. Have study samples collected in-home on Days 5, 14, 28, and 42 4. Agree to return to clinic for additional safety evaluations if needed, as determined by the study team; 5. An aggregate patient-reported COVID-19 symptom score of at ≥3 on the first day of drug administration (Study Day 1). 6. Must agree not to enroll in another study of an investigational agent prior to completion of Day 42 of the study; 7. Able to take ARAKODA according to Prescribing Information 8. Have been symptomatic no longer than 7 days inclusive of Day 1 when the first dose of study medication is administered. 9. 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. 10. Possess a smart phone or tablet, or are willing to utilize a sponsor-provided device if available.
Exclusion criteria
1. Have any of the contraindications for ARAKODA in the prescribing information including: 1. G6PD deficiency 2. Breastfeeding 3. Psychotic disorder or current psychotic symptoms 4. Known hypersensitivity reaction to TQ 2. 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 3. Any other clinically significant acute illness unrelated to COVID-19 within seven days prior to first study drug administration; 4. 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 5. 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 6. 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); 7. Any excluded concomitant medication as described in the ARAKODA package insert. Receipt of a COVID-19 vaccine is not exclusionary; 8. Any COVID-19 symptoms which, in the opinion of the investigator, is suggestive of possible requirement to hospitalize within 48 hours of enrollment. 9. Positive pregnancy test; 10. Are ≥65 years of age and have a clinical frailty score \> 5; 11. Have cystic fibrosis; 12. Have received a transplant; 13. Known to be infected with human immunodeficiency virus (HIV); 14. Have received any B-Cell depleting monoclonal antibody in the last six months; 15. Have a disease or condition which in the opinion of the investigator presents an unacceptable risk of disease progression; 16. Have an aggregate symptom score ≥ 15 and any one of the following risk factors for COVID-19 disease progression: Obesity (BMI ≥31), are a smoker, have never been vaccinated for COVID-19, diabetes with complications, dementia or other neurocognitive disorders, chronic kidney disease, chronic liver disease, COPD or other chronic lung disease, bronchiectasis, coronary atherosclerosis and other heart disease, stroke or other cerebrovascular disease, sickle cell disease or thalassemia, current mood disorder or depression, substance abuse disorder, tuberculosis, cancer that is not invasive squamous and basal carcinomas of the skin or prostate cancer under active surveillance; 17. Have two or more of the following risk factors for COVID-19 disease progression: Obesity (BMI ≥31), are a smoker, diabetes with complications, dementia or other neurocognitive disorders, chronic kidney disease, chronic liver disease, COPD or other chronic lung disease, bronchiectasis, coronary atherosclerosis and other heart disease, stroke or other cerebrovascular disease, sickle cell disease or thalassemia, current mood disorder or depression, substance abuse disorder, tuberculosis, cancer that is not invasive squamous and basal carcinomas of the skin or prostate cancer under active surveillance; 18. Have an aggregate symptom score \>32.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) |
| MCP-1 levels at Days 5, 14 (± 1 day) and 28 (± 2 days) | Days 5, 14 (± 1 day) and 28 (± 2 days) |
| Proportion of patients recovered (first instance) from cough, fever, and shortness of breath at Day 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days) who reported at least one such symptom on Day 1 (recovery defined as in Dow and Smith 2022) | Day 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days) |
| Time to sustained recovery (two, three or four uninterrupted days of recovery) from fever, cough, and shortness of breath at 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days) who reported at least one such symptom on Day 1 | 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days) |
| Proportion of patients recovered (sustained recovery for two, three or four uninterrupted days) from cough, fever, and shortness of breath at Day 14 (± 1 day), Day 28 (± 1 day) and 42 (± 2 days) who reported at least one such symptom on Day 1 | Day 14 (± 1 day), Day 28 (± 1 day) and 42 (± 2 days) |
| Time to first instance of clinical recovery from fever, cough, and shortness of breath at 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days) who reported at least one such symptom on Day 1 (recovery defined as in Dow and Smith 2022) | 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days) |
Other
| Measure | Time frame |
|---|---|
| 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) |
| Proportion of patients recovered from Long Covid symptoms individually and together at Days 14 (± 1 day), 28 (± 2 days) and 42 (± 2 days) | Days 14 (± 1 day), 28 (± 2 days) and 42 (± 2 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 |
| Time to first report by the patient that they feel recovered from COVID-19 symptoms | Time to first report by the patient |
| Cytokine and chemokine levels at Screening, Day 5, Day 14 (± 1 day) and Day 28 (± 2 days) | Screening, Day 5, Day 14 (± 1 day) and Day 28 (± 2 days) |
| Total anti-SARS-CoV-2 spike protein antibody levels (IgM and IgG) at Screening and Day 14 (± 1 day) | Screening and Day 14 (± 1 day) |
| Hospitalization rates due to COVID-19 symptoms (excluding non-COVID 19 causes including admittance for other upper respiratory infections and admittance only for administrative or observations purposes) | Day 42 (± 2 days) |
| Number of unscheduled COVID-19-related medical visits (Doctor's office or emergency room (ER) visit) | Day 42 (± 2 days) |
| Incidence of COVID-19 related neuropsychiatric symptoms (depression, anxiety, impaired wakefulness, memory or ability thinking) | Incidence of COVID-19 related neuropsychiatric symptoms |
| Time to first instance of and sustained recovery from Long Covid symptoms individually and together | Time to first instance of and sustained recovery |
Contacts
Primary ContactGeoff Dow, PhD
Outcome results
None listed