An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge
Phase 2
Recruiting
- Conditions
- Dengue
- Interventions
- Drug: JNJ-64281802 (sentinel high dose)Drug: PlaceboDrug: JNJ-64281802 (remaining high dose)Drug: JNJ-64281802 (medium/low dose)Drug: JNJ-64281802 (daily dosing regimen X)Drug: JNJ-64281802 (weekly dosing regimen Y1)Drug: JNJ-64281802 (weekly dosing regimen Z2)
- Registration Number
- NCT05048875
- Brief Summary
The investigational study drug, JNJ-64281802, is being developed for the prevention and treatment of dengue infection. This study is hypothesizing that the highest dose of the investigational study drug is superior to receiving a placebo with respect to its antiviral activity in healthy adult participants inoculated with Dengue Serotype 3.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 54
Inclusion Criteria
Not provided
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Exclusion Criteria
Not provided
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description JNJ-64281802 JNJ-64281802 (sentinel high dose) There are two cohorts and three groups in each cohort. Cohort 1 consists of Group 1a, Group 1b and Group 2. Cohort 2 consists of Group 3, Group 4, and Group 5. Within each group, participants will either be randomized to receive study drug or placebo. Four participants will be enrolled in Group 1a before enrolling the remaining participants to Group 1b (12 participants) and Group 2 (14 participants) in Cohort 1. Based on the interim analysis results of Cohort 1, three groups for Cohort 2 were created. Eight participants will be enrolled in each of the three groups (Group 3, Group 4, and Group 5). JNJ-64281802 JNJ-64281802 (remaining high dose) There are two cohorts and three groups in each cohort. Cohort 1 consists of Group 1a, Group 1b and Group 2. Cohort 2 consists of Group 3, Group 4, and Group 5. Within each group, participants will either be randomized to receive study drug or placebo. Four participants will be enrolled in Group 1a before enrolling the remaining participants to Group 1b (12 participants) and Group 2 (14 participants) in Cohort 1. Based on the interim analysis results of Cohort 1, three groups for Cohort 2 were created. Eight participants will be enrolled in each of the three groups (Group 3, Group 4, and Group 5). JNJ-64281802 JNJ-64281802 (medium/low dose) There are two cohorts and three groups in each cohort. Cohort 1 consists of Group 1a, Group 1b and Group 2. Cohort 2 consists of Group 3, Group 4, and Group 5. Within each group, participants will either be randomized to receive study drug or placebo. Four participants will be enrolled in Group 1a before enrolling the remaining participants to Group 1b (12 participants) and Group 2 (14 participants) in Cohort 1. Based on the interim analysis results of Cohort 1, three groups for Cohort 2 were created. Eight participants will be enrolled in each of the three groups (Group 3, Group 4, and Group 5). JNJ-64281802 JNJ-64281802 (daily dosing regimen X) There are two cohorts and three groups in each cohort. Cohort 1 consists of Group 1a, Group 1b and Group 2. Cohort 2 consists of Group 3, Group 4, and Group 5. Within each group, participants will either be randomized to receive study drug or placebo. Four participants will be enrolled in Group 1a before enrolling the remaining participants to Group 1b (12 participants) and Group 2 (14 participants) in Cohort 1. Based on the interim analysis results of Cohort 1, three groups for Cohort 2 were created. Eight participants will be enrolled in each of the three groups (Group 3, Group 4, and Group 5). JNJ-64281802 JNJ-64281802 (weekly dosing regimen Y1) There are two cohorts and three groups in each cohort. Cohort 1 consists of Group 1a, Group 1b and Group 2. Cohort 2 consists of Group 3, Group 4, and Group 5. Within each group, participants will either be randomized to receive study drug or placebo. Four participants will be enrolled in Group 1a before enrolling the remaining participants to Group 1b (12 participants) and Group 2 (14 participants) in Cohort 1. Based on the interim analysis results of Cohort 1, three groups for Cohort 2 were created. Eight participants will be enrolled in each of the three groups (Group 3, Group 4, and Group 5). JNJ-64281802 JNJ-64281802 (weekly dosing regimen Z2) There are two cohorts and three groups in each cohort. Cohort 1 consists of Group 1a, Group 1b and Group 2. Cohort 2 consists of Group 3, Group 4, and Group 5. Within each group, participants will either be randomized to receive study drug or placebo. Four participants will be enrolled in Group 1a before enrolling the remaining participants to Group 1b (12 participants) and Group 2 (14 participants) in Cohort 1. Based on the interim analysis results of Cohort 1, three groups for Cohort 2 were created. Eight participants will be enrolled in each of the three groups (Group 3, Group 4, and Group 5). Placebo Placebo There are two cohorts and three groups in each cohort. Cohort 1 consists of Group 1a, Group 1b and Group 2. Cohort 2 consists of Group 3, Group 4, and Group 5. Within each group, participants will either be randomized to receive study drug or placebo. Four participants will be enrolled in Group 1a before enrolling the remaining participants to Group 1b (12 participants) and Group 2 (14 participants) in Cohort 1. Based on the interim analysis results of Cohort 1, three groups for Cohort 2 were created. Eight participants will be enrolled in each of the three groups (Group 3, Group 4, and Group 5).
- Primary Outcome Measures
Name Time Method Assess the antiviral activity of the study drug (JNJ 64281802) versus placebo in terms of reduction of dengue infection. 29 days Area under the DENV-3 RNA viral load (VL) concentration-time curves from immediately before inoculation (baseline on Day 1) until Day 29.
- Secondary Outcome Measures
Name Time Method 12-lead ECG with measurement of QTcF to assess the safety and tolerability of the study drug (JNJ 64281802). 99 weeks Number of adverse events to assess the safety and tolerability of the study drug (JNJ 64281802). 99 weeks Physical examinations to assess the safety and tolerability of the study drug (JNJ 64281802). 99 weeks Recording of vital signs to assess the safety and tolerability of the study drug (JNJ 64281802). 99 weeks Body temperature will be recorded twice daily by study staff and/or by the participants from Day 1 up to and including Day 29; pulse (bpm), systolic and diastolic blood pressure (mmHg) measured on each clinic visit.
Antiviral activity of the study drug (JNJ 64281802) versus placebo based on presence of detectable DENV-3 RNA as measured by PCR (log10 VL) or culture (log10 VL). 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo on area under the infectious viremia curves from immediately before inoculation (baseline on Day 1) until Day 29. 99 weeks 12-lead ECG with measurement of QRS interval to assess the safety and tolerability of the study drug (JNJ 64281802). 99 weeks 12-lead ECG with measurement of PR interval to assess the safety and tolerability of the study drug (JNJ 64281802). 99 weeks Clinical laboratory assessments to assess the safety and tolerability of the study drug (JNJ 64281802). 99 weeks Assess the dengue infection-associated Adverse Events (unwanted medical occurrence). 99 weeks Occurrence and severity of DENV infection associated AEs.
Antiviral activity of the study drug (JNJ 64281802) versus placebo for duration in days of detectable DENV-3 RNA. 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo peak of detectable viremia level 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo on the duration of detectable viremia. 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo on time to first onset of detectable viremia. 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo on presence of detectable viremia. 99 weeks Assess how the body handles the study drug (JNJ-64281802) following repeated oral dosing. Using Pharmacokinetic analysis from repeated blood samples taken at specified time points after drug administration during 2 inpatient stays. 99 weeks Blood samples will be taken for measurement of plasma concentrations of JNJ-64281802 at specific time points in the study. Additional PK sampling may be performed on the non-intensive PK days (eg, in the event of an overdose) on other time points, in consultation with the JNJ drug development team.
Plasma samples will be analyzed to determine concentrations of JNJ-64281802 using a validated, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method under the supervision of the DDT's Bioanalytical Laboratory Department of Bioanalysis.Cmax: maximum observed analyte concentration of JNJ-64281802 99 weeks tmax: the actual sampling time to reach the maximum observed analyte concentration of JNJ-64281802 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo by reviewing the area under the log10-transformed DENV 3 RNA VL concentration-time curves from immediately before inoculation (baseline on Day 1) until Day 29 (AUCD1 D29 [log10 VL]) 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo by reviewing the peak of detectable DENV-3 RNA (log10 VL). 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo time to first onset by days of detectable DENV 3 RNA. 99 weeks Cmin: minimum observed analyte concentration of JNJ-64281802 99 weeks Ctrough: observed analyte concentration just before the beginning or at the end of a dosing interval of JNJ-64281802 99 weeks Cavg: average analyte concentration over the dosing interval (τ) calculated as AUCτ/τ of JNJ-64281802 99 weeks FI: percentage fluctuation (variation) between maximum and minimum analyte concentration at steady-state, calculated as 100 x ([Cmax - Cmin] / Cavg) of JNJ-64281802 99 weeks AUCτ: area under the plasma concentration-time curve during the dosing interval (t hours); calculated by linear-linear trapezoidal summation of JNJ-64281802 99 weeks Occurrence and magnitude of anti-DENV-3 total IgM antibody titers to assess the anti-Dengue immune response. 99 weeks Occurrence and magnitude of anti-DENV-3 total IgG antibody titers to assess the anti-Dengue immune response. 99 weeks Time to first onset of anti-DENV-3 total IgM antibody titers to assess the anti-Dengue immune response. 99 weeks Time to first onset of anti-DENV-3 total IgG antibody titers to assess the anti-Dengue immune response. 99 weeks Antiviral activity of the study drug (JNJ 64281802) versus placebo on the area under the log10-transformed viremia curves. 99 weeks
Trial Locations
- Locations (2)
Johns Hopkins University, Bloomberg School of Public Health
🇺🇸Baltimore, Maryland, United States
University of Vermont Medical Center (UVMMC), Clinical Research Center
🇺🇸Burlington, Vermont, United States