SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02569827

Developed by Shray Alag, 2019.
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: Fever Dengue
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 252
CYBB IL10 TET2 MYD88 IL12A IL12B PRSS1 TREX1 IBA57 NLRP12 POU6F2 SLC29A3 ERCC2 GALC ERCC3 ERCC4 ZBTB16 ABL1 ERCC5 PRTN3 DIS3L2 CRLF1 RNF168 HLA-B SPINK1 ACAT1 AVP ERAP1 HLA-DPA1 AVPR2 HLA-DPB1 CYP11B2 TMEM165 HLA-DRB1 SPTA1 CYP21A2 CYBC1 SPTB CFTR NCF1 PSMB4 GATA2 BLNK PSMB8 SCYL1 PSMB9 PEX6 TCIRG1 SRP54 SLCO1B3 UNC13D PTPN22 IKZF1 NCF2 TSC1 NCF4 TSC2 CCND1 GCH1 HMGCL BCL2 TMEM173 BCL6 ADA BCR ADAR TRIP13 ADA2 F5 LYST DDB2 KLRC4 GFI1 MEFV NLRC4 RYR1 STAT3 STAT4 STAT5B NOD2 STIM1 JAK2 LPIN1 IFIH1 MALT1 PTPN3 DST FBP1 GLA STXBP2 GPC3 BRCA2 KLHL7 POMP PTS KCNJ1 PIK3R1 BTK RNASEH2C EIF2B4 MIF EIF2B3 EIF2B2 EIF2B5 SCNN1A SCNN1B NGF SCNN1G FIP1L1 AK2 CCR1 C4A BCL10 ABCC2 NME1 QDPR RAB27A IL23R NOTCH3 ALPL PML COL1A1 PMM2 MPL PMP22 RNASEH2B CACNA1A NPM1 RAG1 RAG2 CACNA1S TCF4 RANBP2 KRT8 TCF3 HTR1A RARA ANK1 WAS WIPF1 MLX SH2B3 KRT18 RB1 RNASEH2A CALR GPR35 NTRK1 SH3KBP1 NUMA1 SLC19A3 IRF8 WT1 ELP1 BIRC3 XIAP SAMHD1 XPA CHD7 XPC ADAMTS13 LBR REST PSTPIP1 NABP1 RUNX1 FAS AQP2 SLCO1B1 TBL1XR1 EDA ATP13A2 NLRP3 POLR3A SLC4A1 CASK IFNGR1 HAVCR2 MST1 RMRP LIFR ORAI1 LIG4 TH LIPA BCAP31 ATP6 SLC11A1 IL36RN SLC12A1 SLC12A3 COX1 COX2 COX3 IGH DCLRE1C LACC1 CD27 TRIM28 IL12A-AS1 EIF2B1 GYPC IGHM BTNL2 ND1 ND2 ND3 ND4 TLR4 ND5 ND6 LPIN2 CHEK2 PRKAR1A LRRC8A ELANE ZFHX2 CD79A CD79B UBAC2 FOXP1 TRNF TRNH CTLA4 TRNK IGLL1 TRNL1 ATM NGLY1 TNFAIP3 TRNQ TNFRSF1A ATP1A2 ATP1A3 TRNS1 TRNS2 TRNV TRNW HBB STX11 IL2RG G6PD IL6 EPB41 GAA H19 PRNP TP53 EPB42 MVK IL7R CYBA