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

Dengue Fever Clinical Trial

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 Singapore

Status Withdrawn

Clinical Trial 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.

Clinical Trial Description

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 patients will receive capsules Q6H for 5 days prepared by an open-label pharmacist according to the randomisation plan.

Interim Analysis: The treatment regimen chosen for Part 2 will be based on the analysis of Part 1 data. A detailed Statistical Analysis Plan (SAP) will be prepared for approval by the Sponsor prior to performing any unblinded analysis for presentation to personnel designated as being blinded to the randomization. A data safety monitoring board (DSMB) will conduct a blinded review of source verified safety data. If there are no safety concerns, an independent statistician will perform an unblinded futility analysis of preliminary efficacy data from the four cohorts; blinding to treatment group (celgosivir or modipafant) will be maintained, however placebo will be unblinded. If futility is concluded, the Sponsor may elect to discontinue the study. If a signal is detected, a sample size calculation will be undertaken for Part 2. The Sponsor will convene a Scientific Advisory Board (SAB) who will then review unblinded log10 serum viral load AUC for viraemia and platelet count data to recommend which dosing monotherapy dosing regimen to advance to Part 2. If the recommended sample size for Part 2 exceeds the maximum specified for Part 1 and 2 (a total combined sample size of N = 132 participants) for a monotherapy, the Sponsor will submit a major amendment for Institutional Review Board/ Health Science Authority (IRB/HSA) consideration prior to initiating Part 2.

For Part 2, up to 60 otherwise healthy participants with uncomplicated dengue fever meeting the inclusion/exclusion criteria will be assigned in a randomised double-blind fashion to:

• Cohort 5: (i) celgosivir monotherapy 150 mg Q6H, OR (ii) modipafant monotherapy (either 50 mg Q12H or 100 mg Q12H)

• Cohort 6: Placebo extension for 5 days of treatment. ;

Related Conditions & MeSH terms

• Dengue
• Dengue Fever
• Fever

• NCT number: NCT02569827
• Study type: Interventional
• Source: Singapore General Hospital
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: December 2018
• Completion date: August 8, 2019