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Report for Clinical Trial NCT02569827

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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

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.

NCT02569827 Dengue Fever
MeSH: Dengue Fever
HPO: Fever

4 Interventions

Name: Celgosivir

Description: Celgosivir 150 mg Q6H for 5 days (total of 20 doses = 3000 mg celgosivir total).

Type: Drug

Cohort 4

Name: Modipafant 50mg

Description: Modipafant 50 mg Q12H alternating with placebo Q12H for 5 days (total of 10 modipafant doses = 500 mg modipafant)

Type: Drug

Cohort 2

Name: Placebo

Description: Placebo Q6H for 5 days

Type: Drug

Cohort 1

Name: Modipafant 100mg

Description: Modipafant 100 mg Q12H alternating with placebo Q12H for 5 days (total of modipafant 10 doses = 1000 mg modipafant)

Type: Drug

Cohort 3


Primary Outcomes

Description: Area under the curve (AUC) for serum viral load from baseline to Study Day 5 of Celgosivir dosing

Measure: Viral load AUC for viremia

Time: Day 1 to Day 5

Description: Lowest platelet count recorded from baseline to Study Day 5 of Modipafant dosing

Measure: Platelet nadir

Time: Day 1 to Day 5

Secondary Outcomes

Description: 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

Measure: Fever clearance time (days)

Time: Day 1 to 28

Description: 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

Measure: Duration of illness

Time: Day 1 to 28

Description: Determined by comparison of the maximum haematocrit detected in the acute phase as compared to baseline

Measure: Maximum percentage haemoconcentration

Time: Day 1 to 28

Measure: Time to NS1 clearance

Time: Day 1 to 28

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 Q12H

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. --- Q12H ---

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. --- Q12H --- --- Q12H ---



HPO Nodes


HPO:
Fever
Genes 338
GPC3 RANBP2 ND5 BCL10 BIRC3 CCR1 AK2 TRNW LACC1 PRSS2 ND6 QDPR LIG4 PMP22 JAK2 NLRP3 TCIRG1 TRNV BRCA2 ND4 ERCC2 TET2 RNF168 TREX1 CYP21A2 WIPF1 CFTR LIPA EIF2B2 STXBP2 HLA-B AQP2 IBA57 TRNQ IRF2BP2 HMGCL STAT4 MEFV WT1 EPB41 PML PTS CACNA1S GCH1 G6PD HLA-DRB1 GFI1 PEX6 TET2 SLC29A3 RARA PMM2 ABCC2 TREX1 ERCC4 CRLF1 IFNGR1 NOD2 ND2 TNFAIP3 NLRC4 GPR35 CYBC1 HLA-DPA1 IL12B CHEK2 SLC11A1 MYD88 TRIM28 HLA-B TRNF POU6F2 TBL1XR1 FIP1L1 SPTA1 CALR EIF2B1 BCL2 EIF2B3 CYP11B2 COL1A1 TNFRSF1A BCOR HLA-DPB1 PRSS1 MYD88 BCR MEFV ORAI1 IFIH1 ABL1 TP53 LBR IL10 NTRK1 STX11 IGHM DIS3L2 RYR1 ZFHX2 NOTCH3 SH3KBP1 LPIN1 ACAT1 CASK IL12A-AS1 SLC19A3 IL12A NABP1 CALR PSMB8 IL23R RAG2 TSC1 GALC MST1 IL6 CFH IL2RG AQP2 CYP11B2 ND6 ELP1 RUNX1 NUMA1 SPTB NLRC4 CD3E TMEM165 TCF3 SLC29A3 ATP13A2 ND5 ELANE AVP ALPL STAT3 LIFR SPTB CD247 REST SPTA1 LIFR TNFRSF1A CFHR1 EIF2B5 BLNK HMGCL IGH CPT2 CYBB F5 PTPN22 TRIP13 FOXP1 GAA CYBA RYR1 RAG1 GYPC NLRP3 JAK2 TRNH PSMB9 NCF1 RYR1 SLCO1B1 ND3 CD79B LPIN2 RAG1 HTR1A POMP EIF2B4 SRP54 NLRC4 IRF8 ERAP1 TP53 TRNL1 STAT6 PRNP ND4 NGLY1 LYST ATP1A2 KIF1B HAVCR2 CD3D P4HTM SPINK1 MPL SH2B3 SCYL1 IGH MIF C1R POLR3A DCLRE1C LRRC8A TRNS2 IL7R BCL6 NOD2 NLRP3 GATA2 NGF ATM IL2RG PRKAR1A ADAMTS13 IGLL1 PSTPIP1 NLRP12 KRT18 NLRP3 SPP1 TRNS1 CTLA4 CD79A SLC4A1 IL7R NPM1 AVPR2 RNASEH2B PRKAR1A CFHR3 AVPR2 JAK2 KLHL7 H19 IRF8 MPL HAVCR2 TRIM28 FAS CACNA1S NLRP3 TRNL1 NCF2 SLC12A3 WAS PSMB4 WT1 ND1 HLA-DRB1 TLR4 PTPN22 KCNJ1 COX1 STAT4 MVK ERCC5 IKZF1 CCND1 CFTR ADA2 ND1 CD27 NAB2 XIAP PIK3R1 EDA CHD7 IGH LPIN2 ADAR HLA-DRB1 TRNW HLA-DRB1 COX3 SLC12A1 UNC13D RNASEH2C IL36RN ATP1A3 C1QA STING1 NLRP3 NKX2-1 TCF4 TRNK TSC2 PTPN3 RNASEH2A KLRC4 SCNN1B XPA UBAC2 BTK COL1A1 HLA-B COX2 RAB27A CFTR C4A BCAP31 EPB42 RAG2 IRAK1 PRSS1 DDB2 SCNN1A ELANE HBB DST BTNL2 NLRP1 NCF4 MALT1 TH SCNN1G NLRC4 RB1 MEFV MEFV GLA STAT3 SLCO1B3 ADA ZBTB16 STIM1 ATP6 XPC CTRC ERCC3 KRT8 PRTN3 CTRC CACNA1A RMRP FBP1 SPINK1 ANK1 STAT5B NLRP3 SAMHD1 MLX