Clinical Trial: Celgosivir or Modipafant as Treatment for Adult Participants With Uncomplicated Dengue Fever in Singapore

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase Ib/IIa Single Centre, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Dose Ranging Trial in Adult Participants With Uncomplicated Dengue Fever in Si

Brief Summary: Dengue fever is an acute febrile illness transmitted by mosquitoes, which affects half the world's population. There are 96 million symptomatic infections, 500,0000 hospitalisations and 25,000 deaths per year attributed to the disease. The economic burden is $12 billion. In Singapore, as elsewhere, the incidence of the disease continues to increase despite aggressive control measures. At present there are no approved medicines for treating dengue fever. Only supportive fluid replacement therapy is used to treat vascular leakage in patients with severe illness. Therefore there is an urgent need to find alternative treatments. Experiments in the laboratory have shown that Celgosivir and modipafant inhibit dengue virus and improve mouse survival. Both drugs have previously been used in humans with good safety records, so investigators are taking this one step further to find out how well it works in dengue patients. Investigators plan to enroll dengue patients within 48 hours of fever onset and assign them to one of four treatment groups over five days. Together with the support from the industry partner, 60°Pharmaceuticals PLC, the investigators will determine the safety and effectiveness of these drugs on acute dengue patients and pave the way forward for dengue antiviral medicines to reach patients.

Detailed Summary:

This trial is a single centre, double-blind, double-dummy, placebo-controlled parallel-group, dose ranging study in adult participants with uncomplicated dengue fever. The study will be conducted in two parts:

In Part 1, 72 otherwise healthy participants (18 participants per group, assuming up to 2 dropouts per group) with uncomplicated dengue fever meeting the inclusion/exclusion criteria will be randomised to receive treatment with placebo, celgosivir or modipafant. Participants will be randomised in parallel to one of Cohorts 1 to 4:

  • Cohort 1: Placebo Q6Hours for 5 days
  • Cohort 2: Modipafant 50 mg Q12Hours alternating with placebo Q12Hours for 5 days (total of 10 modipafant doses = 500 mg);
  • Cohort 3: Modipafant 100 mg Q12Hours alternating with placebo Q12Hours 5 days (total of 10 modipafant doses = 1000 mg);
  • Cohort 4: Celgosivir 150 mg Q6H for 5 days (total of 20 doses = 3000 mg total).

As modipafant is untested in uncomplicated dengue fever patients, a double-blinded sentinel group consisting of 4 participants randomised in a 1:1:1:1 ratio of Cohort 1: Cohort 2: Cohort 3: Cohort 4 will complete treatment to Study Day 5 prior to continuing enrolment of the remaining participants. Remaining 68 participants will be enrolled in parallel in a double-blinded fashion.

Participants will be evaluated during screening (< 24 hours before Study Day 1) and on Study Days 1-5, 14 and 28. Participants will be confined in the SingHealth Investigational Medicine Unit (IMU) from screening until end of study assessments on Study Day 5 and return to the clinic at Day 14 and 28 as outpatients. All p
Sponsor: Singapore General Hospital

Current Primary Outcome:

  • Viral load AUC for viremia [ Time Frame: Day 1 to Day 5 ]
    Area under the curve (AUC) for serum viral load from baseline to Study Day 5 of Celgosivir dosing
  • Platelet nadir [ Time Frame: Day 1 to Day 5 ]
    Lowest platelet count recorded from baseline to Study Day 5 of Modipafant dosing


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Fever clearance time (days) [ Time Frame: Day 1 to 28 ]
    The time from the start of treatment to the start of the first 24-hour period during which the tympanic or oral temperature remains below 37.5°C
  • Duration of illness [ Time Frame: Day 1 to 28 ]
    A 24-hour reduction in duration of illness that is treatment related is deemed clinically relevant. Draft criteria to support this include: Absence of fever (< 37.4˚C) for at least 24 hours
  • Maximum percentage haemoconcentration [ Time Frame: Day 1 to 28 ]
    Determined by comparison of the maximum haematocrit detected in the acute phase as compared to baseline
  • Time to NS1 clearance [ Time Frame: Day 1 to 28 ]


Original Secondary Outcome: Same as current

Information By: Singapore General Hospital

Dates:
Date Received: October 1, 2015
Date Started: July 2017
Date Completion: August 2018
Last Updated: April 25, 2017
Last Verified: April 2017