Celgosivir as a Treatment Against Dengue (CELADEN)

Celgosivir Proof of Concept Trial for Treatment of Acute Dengue Fever

This is a Randomized, Double-Blind, Placebo-Controlled, Phase 1b Clinical Study to Evaluate the Activity, Pharmacokinetics, Safety and Tolerability of Celgosivir in Adults with Confirmed Dengue Fever.

Study Overview

• Status: Completed
• Conditions: Dengue Fever
• Intervention / Treatment: Drug: celgosivir; Drug: placebo

Detailed Description

Patients with confirmed dengue fever who meet all inclusion and exclusion criteria will be enrolled and admitted to the Investigational Medicine Unit. Patients will be randomized 1:1 to celgosivir or placebo. Capsules of placebo or celgosivir will be administered for 5 days. While in hospital, daily clinical exams will be conducted, and blood samples will be collected for viral load, quantitative NS1, hematology, clinical chemistry, cytokine levels and pharmacokinetics (PK). Safety assessments will be conducted. At discharge on Study Day 5, patients will be asked to return on Study Days 7, 10, and 15 for blood sampling and safety assessments.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Fever of ≥ 38°C of ≤ 48 hr duration.

• At least two of the following criteria indicating probable dengue infection:

  • Live or work in or recent travel to dengue endemic area
  • Nausea and vomiting
  • Presence of rash
  • Aches and pains, including headache, or retro-orbital, muscle or joint pain
• Positive NS1 strip assay

Main Exclusion Criteria:

• Clinical signs and symptoms for severe dengue
• Patients with certain abnormal laboratory values
• History of presently active intestinal disorders
• Severe diarrhea
• Current usage of anticoagulant drugs
• Other clinically significant acute illness
• History of severe drug and/or food allergies
• Exposure to investigational agent within 30 days prior to study drug administration
• Clinically significant abnormal physical exam unrelated to dengue fever
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: placebo; Capsules of identical appearance containing starch
EXPERIMENTAL: Celgosivir	Drug: celgosivir; 100 mg capsules, 400 mg loading dose 200 mg bid; Other Names: Bu-Cast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Virological Log Reduction (Virological Endpoint)	4 days
Fever Reduction (Clinical Endpoint)	4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety-Proportion of patients experiencing adverse events and serious adverse events	The proportion of patients experiencing adverse events and serious adverse events	14 days
Quantitative NS1 and NS1 clearance	NS1 non-structural protein 1	14 days
Hematology	Leukocytes, platelets, hematocrit	14 days
Pharmacokinetics - Clearance of drug (L/hr)	Clearance of drug (L/hr)	5 days

Collaborators and Investigators

• Sponsor: Singapore General Hospital
• Collaborators: Duke-NUS Graduate Medical School
• Investigators: Study Director: Subhash Vasudevan, PhD, Duke-NUS Graduate Medical School

Publications and helpful links

General Publications

• Sung C, Wei Y, Watanabe S, Lee HS, Khoo YM, Fan L, Rathore AP, Chan KW, Choy MM, Kamaraj US, Sessions OM, Aw P, de Sessions PF, Lee B, Connolly JE, Hibberd ML, Vijaykrishna D, Wijaya L, Ooi EE, Low JG, Vasudevan SG. Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients. PLoS Negl Trop Dis. 2016 Aug 10;10(8):e0004851. doi: 10.1371/journal.pntd.0004851. eCollection 2016 Aug.
• Low JG, Sung C, Wijaya L, Wei Y, Rathore APS, Watanabe S, Tan BH, Toh L, Chua LT, Hou Y, Chow A, Howe S, Chan WK, Tan KH, Chung JS, Cherng BP, Lye DC, Tambayah PA, Ng LC, Connolly J, Hibberd ML, Leo YS, Cheung YB, Ooi EE, Vasudevan SG. Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet Infect Dis. 2014 Aug;14(8):706-715. doi: 10.1016/S1473-3099(14)70730-3. Epub 2014 May 28.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: May 15, 2012
• First Submitted That Met QC Criteria: June 14, 2012
• First Posted (ESTIMATE): June 15, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 2, 2013
• Last Update Submitted That Met QC Criteria: November 28, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Hemorrhagic Fevers, Viral; Fever; Dengue
• Other Study ID Numbers: 2012/025/E