Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19

Phase 3

• Conditions: COVID-19
• Interventions: Drug: Dapsone 85 mg PO BID; Drug: Placebo 85 mg PO BID

• Registration Number: NCT04935476
• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary

This is a multi-center, randomized, triple-blind, placebo-controlled (RCT) study to evaluate the efficacy and safety of Dapsone in older adults, and/or in adult patients (≥40yrs of age) with at least one high-risk comorbidity, among those with confirmed SARS-CoV-2 infection.

3000 infected patients diagnosed with COVID-19, non-hospitalized at the time of enrollment, meeting all inclusion and no exclusion criteria will be randomized (1:1 allocation ratio) to receive either Dapsone or placebo tablets for 21 days, and will be followed up for 7 days after treatment termination for outcome assessment and up to 30 days for safety monitoring.

Detailed Description

The primary objective of this study is to determine whether early treatment with Dapsone reduces pulmonary complications related to COVID-19 and consequent hospitalization in high-risk group of elderly adults and adults (≥40yrs of age) with comorbidity.

The secondary objectives are to determine the effect of Dapsone on reducing severe complications related to COVID-19 (ICU, intubation and death) and the safety of treatment with Dapsone in this high-risk COVID-19 patient population.

3000 patients will be enrolled to receive either Dapsone or placebo (1:1 allocation ratio) for 21 days. Follow-up assessments will occur remotely through participant e-daily diary and virtual visits (electronically via internet and/or telephone) at Day 1(start of study drug), 7, 14, 21, 28 and 51 following randomization in order to document the occurrence of any trial endpoints.

Safety and efficacy will be based on data from randomized patients. An independent data and safety monitoring committee (DSMC) will periodically review study results and will make recommendations to the study Steering Committee for continuing the trial as planned (or with modification) or for stopping early for safety concerns.

Study Timeline

• Study First Submitted: 2021-06-21
• Study First Submitted QC: 2021-06-21
• Study First Posted: 2021-06-23
• Study Start: 2021-11-22
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-22
• Last Update Posted: 2022-02-24
• Primary Completion: 2022-03-31
• Study Completion: 2022-07-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 3000

Inclusion Criteria

1. Male or female aged ≥ 40 years;
2. Symptomatic adults with confirmed COVID-19 (SARS-COV-2 PCR positive) for at least 24 hrs. and no more than 7 days: by report or observation, including one or more of the following: temperature ≥ 38°C (≥100.4°F), chills or shivering, cough, difficulty breathing, fatigue, headache, muscle or body ache, anosmia (loss of smell) and/or dysgeusia (loss of taste), GI symptoms (nausea and/or vomiting);

(3a) Aged ≥70 years or above, presence of concomitant comorbidity not required for inclusion

or

(3b) Aged ≥40 to <70 years, and presence of at least one of the following concomitant comorbidities by report, history, or observation:

• Cardiovascular diseases (e.g., hypertension, coronary artery diseases, congestive heart failure, symptomatic arrhythmia, transient brain ischemia, stroke)

• Chronic respiratory diseases (e.g., Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis)

• Obesity (BMI >30 kg/m^2)

• Type 2 Diabetes

• Cancer (participant reported: stable >6 months as per treating doctor/oncologist)

• Autoimmune diseases (T1D, RA, PA, MS, IBD, AD, SS, HT, SLE)

  (4) Participant is considered suitable for continued management in the out-patient setting.

  (5) Non-pregnant non-breastfeeding women of reproductive age group not planning pregnancy and/or adopting advised contraception during the study and for 3 months after the last dose of study medication.

Exclusion Criteria

1. Unable to provide consent; diagnosis of dementia or other significant neurocognitive disorder;
2. Current hospitalization;
3. Patient requiring long term oxygen treatment of > 5 L O2/min because of a chronic lung condition at time of recruitment;
4. Known intolerance/allergy to sulfone;
5. Pregnant or breastfeeding women or is considering becoming pregnant during the study and for 3 months after the last dose of study medication;
6. Concurrent malignancy on systemic chemotherapy or immunotherapy;
7. Significantly impaired renal function within the past year reported by history and estimated glomerular filtration rate (eGFR) < 60 mL/min at screening
8. Severely underweight (≤ 40 kg)
9. G6PD deficiency (previous jaundice, jaundice with foods such as beans, or medication such as sulfa drugs, NSAIDs, quinolones, hydroxychloroquine or vitamin C), significant blood dyscrasia or anemia (Hb <12.0 g/dL in women and <13.0 g/dL in men; platelet count <50 x 10^9/L or < lower limit of normal at screening)
10. Impairment liver function [> 2 times the upper limit of normal (ULN) at screening at screening for AST, ALT, ALP, GGT, albumin or bilirubin), liver cirrhosis or hepatitis
11. Current use of folic acid antagonists (such as pyrimethamine), nitrofurantoin or primaquine
12. Currently taking oral dapsone for dermatological or other indications
13. Currently taking hydroxychloroquine or if have taken it within the last 6 months
14. Currently on any of the following medications: Aminolevulinic acid; Cladribine; Clozapine; Deferiprone; Prilocaine; Saquinavir; Sodium nitrite, Rifampin or St. John's wort
15. Received any of the following vaccines in the last 1 year : Cholera vaccine live; Typhoid vaccine, live; BCG (Bacillus Calmette and Guérin)
16. Currently taking any the following anticonvulsants : carbamazepine, phenytoin, levetiracetam and gabapentin
17. Currently participating in other interventional trials
18. Inability to provide contact details of caregiver/ next of kin to be contacted for study follow-up as participant's surrogate
19. Currently taking trimethoprim

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment	Dapsone 85 mg PO BID	Participants will receive standard of care and Dapsone per os (PO) twice daily for 21 days. If a dose is missed, it should not be replaced. Dosage form: Dapsone oral tablet
Control	Placebo 85 mg PO BID	Participants will receive standard of care and placebo per os (PO) twice daily for 21 days. If a dose is missed, it should not be replaced. Dosage form: Placebo oral tablet

Primary Outcome Measures

Name	Time	Method
Composite outcome: All cause pre-hospitalization death or all-cause hospitalization	30 days post randomization	Number of participants requiring hospitalization or die prior to hospitalization in the first 30 days after randomization.

Secondary Outcome Measures

Name	Time	Method
Severe complications (composite outcome: All cause ICU admission, invasive ventilation or pre- or post-hospitalization death)	30 days post randomization	Number of participants developing severe complications and need ICU admission, invasive ventilation or die in the first 30 days.
All-cause ICU admission	30 days post randomization	Number of participants requiring ICU admission in the first 30 days after randomization.
Intubation with mechanical ventilation	30 days post randomization	Number of participants requiring intubation with mechanical ventilation in the first 30 days after randomization.
All-cause death	30 days post randomization	Number of participants who die in the first 30 days after randomization.
Hospitalization with all-cause requirement of supplemental oxygen	30 days post randomization	Number of participants requiring hospitalization with supplemental oxygen in the first 30 days after randomization.
Length of hospital stay among participants	30 days post randomization	Duration of hospitalization among study participants requiring hospitalization in the first 30 days after randomization.
Drug safety (Adverse Event (AE) and Serious Adverse Event (SAE)) for short term therapy in COVID-19 patients	30 days post randomization	Number of participants developing AE and SAE in the first 30 days post randomization.
Patient reported outcome (e.g. patient reported COVID-19 related symptoms)	30 days post randomization	Trajectory of participant reported COVID-19 related symptoms among study participants in the first 30 days after randomization.

Trial Locations

Locations (7)

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

University of Pittsburgh UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Arizona Pulmonary and Medical Specialists; 🇺🇸 Phoenix, Arizona, United States

Inspiration Research Limited; 🇨🇦 Toronto, Ontario, Canada

Temple University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Peters Medical Research, LLC; 🇺🇸 High Point, North Carolina, United States

Principle Research Solutions; 🇺🇸 Spokane, Washington, United States