A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste

Abstract

Importance: Early treatment of mild SARS-CoV-2 infection might lower the risk of clinical deterioration in COVID-19. Objective: To determine whether oral camostat mesylate would reduce upper respiratory SARS-CoV-2 viral load in newly diagnosed outpatients with mild COVID-19, and would lead to improvement in COVID-19 symptoms. Design: From June, 2020 to April, 2021, we conducted a randomized, double-blind, placebo-controlled phase 2 trial. Setting: Single site, academic medical center, outpatient setting in Connecticut, USA. Participants: Of 568 COVID-19 positive potential adult participants diagnosed within 3 days of study entry and assessed for eligibility, 70 were randomized and 498 were excluded (198 did not meet eligibility criteria, 37 were not interested, 265 were excluded for unknown or other reasons). The primary inclusion criteria were a positive SARS-CoV-2 nucleic acid amplification result in adults within 3 days of screening regardless of COVID-19 symptoms. Intervention: Treatment was 7 days of oral camostat mesylate, 200 mg po four times a day, or placebo. Main Outcomes and Measures: The primary outcome was reduction of 4-day log10 nasopharyngeal swab viral load by 0.5 log10 compared to placebo. The main prespecified secondary outcome was reduction in symptom scores as measured by a quantitative Likert scale instrument, Flu-PRO-Plus modified to measure changes in smell/taste measured using FLU-PRO-Plus. Results: Participants receiving camostat had statistically significant lower quantitative symptom scores (FLU-Pro-Plus) at day 6, accelerated overall symptom resolution and notably improved taste/smell, and fatigue beginning at onset of intervention in the camostat mesylate group compared to placebo. Intention-to-treat analysis demonstrated that camostat mesylate was not associated with a reduction in 4-day log10 NP viral load compared to placebo. Conclusions and relevance: The camostat group had more rapid resolution of COVID-19 symptoms and amelioration of the loss of taste and smell. Camostat compared to placebo was not associated with reduction in nasopharyngeal SARS-COV-2 viral load. Additional clinical trials are warranted to validate the role of camostat mesylate on SARS-CoV-2 infection in the treatment of mild COVID-19. Trial registration: Clinicaltrials.gov, NCT04353284 (04/20/20) (https://clinicaltrials.gov/ct2/show/NCT04353284?term=camostat+%2C+yale&draw=2&rank=1)

A multicenter, double-blind, randomized, parallel-group, placebo-controlled study to evaluate the efficacy and safety of camostat mesilate in patients with COVID-19 (CANDLE study)

“…Additionally, a US study of outpatients treated with camostat mesilate at a dose of 200 mg four times daily for 7 days did not achieve a reduction in viral load compared with placebo [24]. Interestingly, the efficacy of camostat mesilate was not confirmed by the primary endpoint of viral load, but camostat mesilate prevented the loss of smell/taste compared with placebo.…”

Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19

“…The trial did not, however, achieve the primary endpoint of reducing the viral load by PCR in the upper respiratory tract. 34 …”

Molecular mechanisms involved in anosmia induced by SARS-CoV-2, with a focus on the transmembrane serine protease TMPRSS2

“…A clinical trial on 95 patients who received 200 mg of camostat mesylate three times per day for 2 weeks for the treatment of dyspepsia associated with non-alcoholic mild pancreatic disease demonstrated only mild adverse effects [ 143 ], indicating that this drug is well tolerated [ 29 ]. A clinical trial demonstrated a more rapid resolution of COVID-19 symptoms and amelioration of lost taste and smell in outpatients with newly diagnosed mild COVID-19 infection who received oral camostat mesylate [ 30 ]. Nafamostat mesylate is a synthetic serine protease that is clinically approved in Japan to treat disseminated intravascular coagulation and acute pancreatitis.…”

“…Nafamostat mesylate and camostat mesylate are synthetic serine protease inhibitors with the ability to impair viral entry. In a clinical trial involving newly diagnosed outpatients with mild infection, oral camostat mesylate was shown to reduce the viral load of respiratory SARS-CoV-2, leading to rapid resolution of symptoms related to COVID-19 and amelioration of loss of smell and taste [ 30 ]. Thus, precise information about the functions of the TMPRSS2 receptor could aid in the development of therapeutic strategies against COVID-19 and its related complications, including anosmia.…”