Clinical trial NCT04935476: Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19
Official title: A Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of Dapsone for the Treatment of COVID-19 Positive Patients.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19
Keywords: Dapsone
COVID-19
treatment for COVID-19
non-hospitalized patients
prophylaxis
SARS-COV-2
Clinical trials
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Pulmonem Inc.
First posted: 2021-06-23
Enrollment: 3000
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, triple-blind, placebo-controlled, multi-center study.

Following e-signature of the informed consent form, approximately 3000 participants meeting all inclusion criteria and no exclusion criteria will be randomized to receive either Dapsone or placebo (1:1 allocation ratio) for 21 days. Screening blood-work and confirmatory tests are made available to participants at their residence by the study. Study interventions (drugs or placebo) will be delivered directly to participants by courier .

Participants are remotely followed-up through e-daily diary during 21 days of treatment along with virtual visits (phone) at 1, 7, 14, 21, 28 and 51 days following randomization for evaluation of the occurrence of any trial endpoints or other adverse events. During study enrollment patients are linked to the study through their participant account on the study virtual care platform.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite outcome: All cause pre-hospitalization death or all-cause hospitalization
timeFrame: 30 days post randomization
Secondary outcomes:
measure: Severe complications (composite outcome: All cause ICU admission, invasive ventilation or pre- or post-hospitalization death)
timeFrame: 30 days post randomization
measure: All-cause ICU admission
timeFrame: 30 days post randomization
measure: Intubation with mechanical ventilation
timeFrame: 30 days post randomization
measure: All-cause death
timeFrame: 30 days post randomization
measure: Hospitalization with all-cause requirement of supplemental oxygen
timeFrame: 30 days post randomization
measure: Length of hospital stay among participants
timeFrame: 30 days post randomization
measure: Drug safety (Adverse Event (AE) and Serious Adverse Event (SAE)) for short term therapy in COVID-19 patients
timeFrame: 30 days post randomization
measure: Patient reported outcome (e.g. patient reported COVID-19 related symptoms)
timeFrame: 30 days post randomization
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Pulmonary and Medical Specialists
state: Arizona
city: High Point
country: United States
facility: Peters Medical Research, LLC
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh UPMC
state: Pennsylvania
city: Spokane
country: United States
facility: Principle Research Solutions
state: Washington
city: Toronto
country: Canada
facility: Inspiration Research Limited
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: RI-MUHC
name: Jean Bourbeau, MD,MSc,FRCPC
role: PRINCIPAL_INVESTIGATOR
References: