Dengue FeverPhase 1/2NCT02569827
Celgosivir or Modipafant as Treatment for Adult Participants With Uncomplicated Dengue Fever in Singapore
A Phase 1/2 study testing Celgosivir, Modipafant 50mg and Modipafant 100mg in people with Dengue Fever, run by Singapore General Hospital at 1 site in Singapore.
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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Dengue Fever
- What is being tested?
- Celgosivir, Modipafant 50mg and Modipafant 100mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteSingapore
- Study dates
- Dec 2018to 8 Aug 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, aged 21-65 years;
- Acute febrile illness with two or more manifestations (headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations, or leucopoenia) and occurrence at the same location and time as other confirmed cases of dengue fever;
- Fever (> 37.5°C) or history of fever at screening
- < 48 hours of fever history
- Positive NS1 strip assay or reverse-transcriptase polymerase chain reaction (RT-PCR).
- Able and willing to give written informed consent; and,
- Willing to be an inpatient from Study Screening to Study Day 5 and to return to hospital on study Days 14 and 28.
- Willing to keep a study diary from Study Day 5 to Day 14.
Who cannot join
- Clinical signs and symptoms for severe dengue, such as:
- Severe abdominal pain;
- Persistent vomiting;
- CS fluid accumulation;
- Mucosal bleeding;
- Altered mental state;
Show all 31Show fewer
- Liver enlargement > 2 cm;
- Systolic blood pressure < 90 mmHg; and
- Pulse pressure < 20 mmHg.
- A person with any of the following laboratory values:
- Haematocrit >52% males; >46% females;
- Aspartate or alanine aminotransferase (AST or ALT) > 1000 U/L;
- Room air oxygen saturation < 95%;
- Absolute neutrophil count < 1500/µL;
- Platelet count < 80,000/mm3;
- Creatinine > 165 µmol/L males; > 130 µmol/L females;
- Haemoglobin < 13.0 g/dL males; < 11.0 g/dL females;
- Total bilirubin > 24 µmol/L; and
- Serum CPK > 600 U/L.
- History of or presently active intestinal disorders such as peptic ulcers, intestinal ulcers, intestinal obstructions, intestinal hernias, ulcerative colitis, malabsorption syndrome, celiac disease, Roemheld's syndrome (gastroesophageal regurgitation disease) or Crohn's disease;
- Severe diarrhoea (grade 2 or higher according to NIH clinical trial guidelines);
- Current usage of any anticoagulant drugs including, but not limited to, aspirin, warfarin or clopidogrel;
- Any other CS acute illness within seven days prior to first study drug administration;
- History of adverse reactions to celgosivir, castanospermine, modipafant or formulation excipients or history of severe drug or food allergies;
- Exposure to any new investigational drug within 30 days prior to the study drug administration;
- CS abnormal physical examination unrelated to dengue infection, chest X-ray or 12-lead ECG at screening such as QTc prolongation (> 450 msec);
- Women of child bearing potential (WOCBP) who are pregnant, breast feeding or unwilling to avoid pregnancy by the use of highly effective contraception (<1% failure rate per year) including oral and subcutaneous implantable hormonal contraceptives, condoms, diaphragm, or intra-uterine system (IUS), during the period that the experimental drug is administered. Prospective WOCBP must have a negative pregnancy test (point of care).
- Male participants unwilling to comply with the contraceptive requirements of the study as detailed in Section 4.7 (i.e. abstinence, effective barrier contraception during the study and for 65 days after the last dose of study drug).
- Current significant medical condition or illness including cardiac arrhythmias, cardiomyopathy or other cardiac disease, asthma or other respiratory disease, diabetes mellitus, renal or hepatic impairment, thyroid disease, Parkinson's disease, epilepsy or history of unexplained blackouts, immunocompromised state including known HIV infection, or any other illness that the Investigator considers should exclude the patient, especially those that require continuation of other medications likely to have an interaction with the study drug.
- Any condition that would render the informed consent invalid, or limit the ability of the participant to comply with the study requirements.
- Any condition that, in the opinion of the Investigator, would complicate or compromise the study or well-being of the participant.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed 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.
- Conditions
- Dengue Fever
- Being tested
- Celgosivir, Modipafant 50mg, Placebo, Modipafant 100mg
- Keywords
- Uncomplicated Dengue Fever, Treatment, Phase Ib/IIa, single centre, double-blind, placebo-controlled, parallel-group dose ranging trial, Modipafant, Celgosivir
- Medical subject headings
- Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CelgosivirDrug
Celgosivir 150 mg Q6H for 5 days (total of 20 doses = 3000 mg celgosivir total).
Modipafant 50mgDrug
Modipafant 50 mg Q12H alternating with placebo Q12H for 5 days (total of 10 modipafant doses = 500 mg modipafant)
PlaceboDrug
Placebo Q6H for 5 days
Modipafant 100mgDrug
Modipafant 100 mg Q12H alternating with placebo Q12H for 5 days (total of modipafant 10 doses = 1000 mg modipafant)
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Placebo comparator | Placebo Q6H for 5 days
A total of 72 participants (18 participants per group assuming up to two drop-outs per group) will be assigned in a randomised double-blind fashion. Receives: Drug: Placebo |
| Cohort 2 | Active comparator | Modipafant 50 mg Q12H alternating with placebo Q12H for 5 days (total of 10 modipafant doses = 500 mg) Receives: Drug: Modipafant 50mg |
| Cohort 3 | Active comparator | Modipafant 100 mg Q12H alternating with placebo Q12H 5 days (total of 10 modipafant doses = 1000 mg) Receives: Drug: Modipafant 100mg |
| Cohort 4 | Active comparator | Celgosivir 150 mg Q6H for 5 days (total of 20 doses = 3000 mg total). Receives: Drug: Celgosivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Viral load AUC for viremia
Area under the curve (AUC) for serum viral load from baseline to Study Day 5 of Celgosivir dosing
Measured: Day 1 to Day 5
Platelet nadir
Lowest platelet count recorded from baseline to Study Day 5 of Modipafant dosing
Measured: Day 1 to Day 5
Secondary outcomes (4)
Fever clearance time (days)
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
Measured: Day 1 to 28
Duration of illness
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
Measured: Day 1 to 28
Maximum percentage haemoconcentration
Determined by comparison of the maximum haematocrit detected in the acute phase as compared to baseline
Measured: Day 1 to 28
Time to NS1 clearance
Measured: Day 1 to 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2015 (estimated)
- Study startDec 2018 (estimated)
- Primary completion8 Aug 2019
- Study completion8 Aug 2019
Why it stopped: The investigational drug celgosivir will not be developed due to lack of VC funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Dengue FeverStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Duke-NUS Graduate Medical School, 60 Degrees Pharmaceuticals LLC
- Responsible party
- Sponsor
- Investigators
- Jenny Low, Dr, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02569827
- Sponsor's protocol ID
- Cel01
- Status last verified
- Mar 2020
- First submitted
- 1 Oct 2015
- Last updated
- 23 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 24877997Rathore AP, Paradkar PN, Watanabe S, Tan KH, Sung C, Connolly JE, Low J, Ooi EE, Vasudevan SG. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Res. 2011 Dec;92(3):453-60. doi: 10.1016/j.antiviral.2011.10.002. Epub 2011 Oct 12.
PubMed 22020302Watanabe S, Rathore AP, Sung C, Lu F, Khoo YM, Connolly J, Low J, Ooi EE, Lee HS, Vasudevan SG. Dose- and schedule-dependent protective efficacy of celgosivir in a lethal mouse model for dengue virus infection informs dosing regimen for a proof of concept clinical trial. Antiviral Res. 2012 Oct;96(1):32-5. doi: 10.1016/j.antiviral.2012.07.008. Epub 2012 Jul 31.
PubMed 22867971Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS. Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo. J Virol. 2005 Jul;79(14):8698-706. doi: 10.1128/JVI.79.14.8698-8706.2005.
PubMed 15994763Watanabe S, Chan KW, Dow G, Ooi EE, Low JG, Vasudevan SG. Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy. Antiviral Res. 2016 Mar;127:10-9. doi: 10.1016/j.antiviral.2015.12.008. Epub 2016 Jan 13.
PubMed 26794905
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02569827
- Acronym / sponsor ID
- Cel01
- Conditions
- Dengue Fever
- Keywords
- Uncomplicated Dengue Fever, Treatment, Phase Ib/IIa, single centre, double-blind, placebo-controlled, parallel-group dose ranging trial, Modipafant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The investigational drug celgosivir will not be developed due to lack of VC funding.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Collaborators
- Duke-NUS Graduate Medical School, 60 Degrees Pharmaceuticals LLC
- Study start
- Dec 2018 (estimated)
- Primary completion
- 8 Aug 2019 (actual)
- Study completion
- 8 Aug 2019 (actual)
- First posted
- 7 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Placebo comparator | Drug: PlaceboPlacebo Q6H for 5 days A total of 72 participants (18 participants per group assuming up to two drop-outs per group) will be assigned in a randomised double-blind fashion. |
| Cohort 2 | Active comparator | Drug: Modipafant 50mgModipafant 50 mg Q12H alternating with placebo Q12H for 5 days (total of 10 modipafant doses = 500 mg) |
| Cohort 3 | Active comparator | Drug: Modipafant 100mgModipafant 100 mg Q12H alternating with placebo Q12H 5 days (total of 10 modipafant doses = 1000 mg) |
| Cohort 4 | Active comparator | Drug: CelgosivirCelgosivir 150 mg Q6H for 5 days (total of 20 doses = 3000 mg total). |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female, aged 21-65 years;
- Acute febrile illness with two or more manifestations (headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations, or leucopoenia) and occurrence at the same location and time as other confirmed cases of dengue fever;
- Fever (> 37.5°C) or history of fever at screening
- < 48 hours of fever history
- Positive NS1 strip assay or reverse-transcriptase polymerase chain reaction (RT-PCR).
Key exclusion criteria (31 listed)
- Clinical signs and symptoms for severe dengue, such as:
- A person with any of the following laboratory values:
- History of or presently active intestinal disorders such as peptic ulcers, intestinal ulcers, intestinal obstructions, intestinal hernias, ulcerative colitis, malabsorption syndrome, celiac disease, Roemheld's syndrome (gastroesophageal regurgitation disease) or Crohn's disease;
- Severe diarrhoea (grade 2 or higher according to NIH clinical trial guidelines);
- Current usage of any anticoagulant drugs including, but not limited to, aspirin, warfarin or clopidogrel;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CelgosivirCelgosivir 150 mg Q6H for 5 days (total of 20 doses = 3000 mg celgosivir total). | Drug | Cohort 4 |
| Modipafant 50mgModipafant 50 mg Q12H alternating with placebo Q12H for 5 days (total of 10 modipafant doses = 500 mg modipafant) | Drug | Cohort 2 |
| PlaceboPlacebo Q6H for 5 days | Drug | Cohort 1 |
| Modipafant 100mgModipafant 100 mg Q12H alternating with placebo Q12H for 5 days (total of modipafant 10 doses = 1000 mg modipafant) | Drug | Cohort 3 |
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
4 secondary outcomes
Fever clearance time (days)
Time frame: Day 1 to 28
Duration of illness
Time frame: Day 1 to 28
Maximum percentage haemoconcentration
Time frame: Day 1 to 28
Time to NS1 clearance
Time frame: Day 1 to 28
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2020.
- Background: PubMed 24877997Low 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.
- Background: PubMed 22020302Rathore AP, Paradkar PN, Watanabe S, Tan KH, Sung C, Connolly JE, Low J, Ooi EE, Vasudevan SG. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Res. 2011 Dec;92(3):453-60. doi: 10.1016/j.antiviral.2011.10.002. Epub 2011 Oct 12.
- Background: PubMed 22867971Watanabe S, Rathore AP, Sung C, Lu F, Khoo YM, Connolly J, Low J, Ooi EE, Lee HS, Vasudevan SG. Dose- and schedule-dependent protective efficacy of celgosivir in a lethal mouse model for dengue virus infection informs dosing regimen for a proof of concept clinical trial. Antiviral Res. 2012 Oct;96(1):32-5. doi: 10.1016/j.antiviral.2012.07.008. Epub 2012 Jul 31.
- Background: PubMed 15994763Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS. Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo. J Virol. 2005 Jul;79(14):8698-706. doi: 10.1128/JVI.79.14.8698-8706.2005.
- Derived from this study: PubMed 26794905Watanabe S, Chan KW, Dow G, Ooi EE, Low JG, Vasudevan SG. Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy. Antiviral Res. 2016 Mar;127:10-9. doi: 10.1016/j.antiviral.2015.12.008. Epub 2016 Jan 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jenny Low, Dr principal investigator
Singapore General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Celgosivir, Modipafant 50mg and Modipafant 100mg in people with Dengue Fever, run by Singapore General Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Viral load AUC for viremia (time frame: Day 1 to Day 5). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02569827, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2020.