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

McGill University

Status and phase: Unknown; Phase 3

Conditions: COVID-19

Treatments: Drug: Placebo 85 mg PO BID; Drug: Dapsone 85 mg PO BID

Study type: Interventional

Funder types: Other

Identifiers

NCT04935476

PDC01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3,000 estimated patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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3,000 participants in 2 patient groups, including a placebo group

Treatment

Active Comparator group

Description:

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

Treatment:

Drug: Dapsone 85 mg PO BID

Control

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo 85 mg PO BID