Dengue
Conditions
Brief summary
The purpose of this study is to investigate the antiviral activity of JNJ-64281802 versus placebo in terms of reduction of dengue virus (DENV) ribonucleic acid (RNA) in primary DENV infection.
Interventions
DRUGJNJ-64281802
JNJ-64281802 will be administered orally.
DRUGPlacebo
Matching placebo (PEG400) will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Participant with a referral note/documentation from a health care facility or practitioner indicating non-structural 1 protein (NS1) positive for dengue virus (DENV), positive NS1 rapid test at pre-screening during an ambulatory visit, or participant who tests NS1 positive at the site * Participant reported a fever with an onset within the last 48 hours * A woman of childbearing potential must have a negative serum pregnancy test at screening * A woman must be: a. not of childbearing potential, b. of childbearing potential and practicing a highly effective, preferably user-independent method of contraception (failure rate of less than \[\<\] 1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until at least 90 days after last dose- the end of relevant systemic exposure * A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study intervention
Exclusion criteria
* Participant with any clinical signs and symptoms for severe dengue according to the world health organization (WHO) criteria (such as severe plasma leakage leading to dengue shock syndrome \[DSS\], fluid accumulation with respiratory distress, severe bleeding, sever organ involvement) * Use of any cytochrome 3A4 (CYP3A4) inducers (example, phenytoin, rifampin), UDP glucuronosyltransferase family 1 member A9 (UGT1A9) inducers (example, rifampin), or substrates for CYP3A4 with a narrow therapeutic range (example, alfentanil, cyclosporin), or sensitive breast cancer resistance protein (BCRP) substrates (example, pravastatin and folic acid) from 14 days before first dose of study drug until 28 days after last dose of study drug. Systemic use of strong CYP3A4 inhibitors (example, clarithromycin, itraconazole) or UGT1A9 inhibitors (example, probenecid, mefenamic acid) from 7 days before first dose of study drug until 28 days after last dose of study drug * History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence) * Had major surgery, (example, requiring general anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study * Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Log10-Transformed Dengue Virus (DENV) RiboNucleic Acid (RNA) Viral Load (VL) Curve From Baseline Until Day 5 (AUCD1-D5 [log10VL]). | Baseline (Day 1) upto Day 5 | The antiviral activity of JNJ-64281802 versus placebo in terms of reduction of DENV RNA in participants with a primary DENV infection was planned to be measured by the area under the log10-transformed DENV RNA viral load concentration-time curves from baseline (Day 1) until Day 5 (AUCD1-D5 \[log10VL\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | From Day 1 up to the last onsite visit (Day 30) | Number of participants with clinically significant abnormalities in ECGs parameters as assessed based on investigator's discretion were reported. |
| Number of Participants With Clinically Significant Abnormalities in Physical Examination | From Day 1 up to the last onsite visit (Day 30) | Number of participants with clinically significant abnormalities in physical examination parameters (head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological) as assessed based on investigator's discretion were reported. |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | From Day 1 up to the last onsite visit (Day 30) | Number of participants with clinically significant abnormalities in vital signs (temperature, pulse/heart rate, respiratory rate, peripheral capillary oxygen saturation \[spO2\], input-output \[I/O\] ratio and blood pressure) as assessed based on investigator's discretion were reported. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | From Day 1 up to the last onsite visit (Day 30) | Number of participants with clinically significant abnormalities in laboratory parameters (serum chemistry, hematology, and coagulation) were reported. Clinical significance was defined as per investigator's judgement. |
| Plasma Concentrations of JNJ-64281802 | Predose: 0, 8, 16 hours on Day 1; 24, 32, 40 hours on Day 2; Day 4, Day 5; and Post dose: 4, 12 hours on Day 1; 28, 36 hours on Day 2; 48 hours on Day 3; Day 6, Day 14, Day 21, Day 28 | Plasma Concentrations of JNJ-64281802 was assessed. Due to small number of enrolled participants, no summary statistics analysis was performed. Participant wise data were reported for this outcome measure. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From Day 1 up to the last onsite visit (Day 30) | An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were those AE events that occurred at or after the initial administration of study intervention through the last onsite visit. |
| Time to Undetectable Dengue Virus (DENV) RiboNucleic Acid (RNA) in Primary DENV Infection | Predose: 24 hour on Day 2; Post dose: 12 hour on Day 1; 36 hour on Day 2; Days 3, 4, 5, 6, 7, 8, 9, 14, 21 and 28 | Time to undetectable DENV RNA in primary DENV infection was a planned analysis. |
| Area Under the Plasma Concentration Time Curve During One Dosing Interval (AUC[Tau]) of JNJ-64281802 | 0, 8, 16 hours pre-dose on Day 1; 4 and 12 hours post-dose on Day 1 | AUC\[tau\] is defined as area under the plasma concentration time curve during one dosing interval of JNJ-64281802. |
| Trough (Pre-dose) Analyte Concentration (Ctrough) of JNJ-64281802 | Pre-dose on Day 1: 0 hour, 8 hour, 16 hour; pre-dose on Day 2: 24 hour, 32 hour, 40 hour; pre-dose on Day 4 and Day 5 | Ctrough is defined as plasma concentration just prior to the beginning or at the end of a dosing interval of JNJ-64281802. |
| Maximum Observed Plasma Concentration (Cmax) of JNJ-64281802 | 0, 8, 16 hours pre-dose on Day 1; 4 and 12 hours post-dose on Day 1 | Cmax is defined as the maximum observed plasma concentration of JNJ-64281802. |
| Number of Participants With Occurrence of Detectable Dengue Virus (DENV) RiboNucleic Acid (RNA) in Primary DENV Infection | Predose: 24 hour on Day 2; Post dose: 12 hour on Day 1; 36 hour on Day 2; Days 3, 4, 5, 6, 7, 8, 9, 14, 21 and 28 | Number of participants with occurrence of detectable DENV RNA in primary DENV infection was a planned analysis. |
Countries
Singapore
Participant flow
Pre-assignment details
Due to small number of enrolled participants, planned data collection and analysis was not performed for the efficacy objectives and no data was reported for efficacy outcome measures and thus only safety analysis data were reported.
Participants by arm
| Arm | Count |
|---|---|
| JNJ-64281802 Participants received 2 initial loading dose of JNJ-64281802 up to Day 2, followed by a maintenance dose on Days 3, 4, and 5. | 2 |
| Placebo Participants received oral dose of placebo matching to JNJ-64281802 every 8 hour (q8h) and once daily on Day 4 and Day 5. | 3 |
| Total | 5 |
Baseline characteristics
| Characteristic | JNJ-64281802 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Continuous | 47 years STANDARD_DEVIATION 9.9 | 37.7 years STANDARD_DEVIATION 9.5 | 41.4 years STANDARD_DEVIATION 9.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment SINGAPORE | 2 participants | 3 participants | 5 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 3 |
| other Total, other adverse events | 2 / 2 | 3 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 3 |
Outcome results
Primary
Area Under the Log10-Transformed Dengue Virus (DENV) RiboNucleic Acid (RNA) Viral Load (VL) Curve From Baseline Until Day 5 (AUCD1-D5 [log10VL]).
The antiviral activity of JNJ-64281802 versus placebo in terms of reduction of DENV RNA in participants with a primary DENV infection was planned to be measured by the area under the log10-transformed DENV RNA viral load concentration-time curves from baseline (Day 1) until Day 5 (AUCD1-D5 \[log10VL\]).
Time frame: Baseline (Day 1) upto Day 5
Population: Due to the small number of enrolled participants, planned data collection and analysis was not performed and thus no data was reported for this outcome measure.
Secondary
Area Under the Plasma Concentration Time Curve During One Dosing Interval (AUC[Tau]) of JNJ-64281802
AUC\[tau\] is defined as area under the plasma concentration time curve during one dosing interval of JNJ-64281802.
Time frame: 0, 8, 16 hours pre-dose on Day 1; 4 and 12 hours post-dose on Day 1
Population: Due to small number of enrolled participants, formal analysis was not performed for the planned PK parameters and thus no data was reported for this outcome measure
Secondary
Maximum Observed Plasma Concentration (Cmax) of JNJ-64281802
Cmax is defined as the maximum observed plasma concentration of JNJ-64281802.
Time frame: 0, 8, 16 hours pre-dose on Day 1; 4 and 12 hours post-dose on Day 1
Population: Due to small number of enrolled participants, formal analysis was not performed for the planned PK parameters and thus no data was reported for this outcome measure
Secondary
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
Number of participants with clinically significant abnormalities in ECGs parameters as assessed based on investigator's discretion were reported.
Time frame: From Day 1 up to the last onsite visit (Day 30)
Population: Safety population included all randomized participants who had taken at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64281802 | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Number of participants with clinically significant abnormalities in laboratory parameters (serum chemistry, hematology, and coagulation) were reported. Clinical significance was defined as per investigator's judgement.
Time frame: From Day 1 up to the last onsite visit (Day 30)
Population: Safety population included all randomized participants who had taken at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64281802 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | 3 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Physical Examination
Number of participants with clinically significant abnormalities in physical examination parameters (head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological) as assessed based on investigator's discretion were reported.
Time frame: From Day 1 up to the last onsite visit (Day 30)
Population: Safety population included all randomized participants who had taken at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64281802 | Number of Participants With Clinically Significant Abnormalities in Physical Examination | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormalities in Physical Examination | 1 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Number of participants with clinically significant abnormalities in vital signs (temperature, pulse/heart rate, respiratory rate, peripheral capillary oxygen saturation \[spO2\], input-output \[I/O\] ratio and blood pressure) as assessed based on investigator's discretion were reported.
Time frame: From Day 1 up to the last onsite visit (Day 30)
Population: Safety population included all randomized participants who had taken at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64281802 | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
Secondary
Number of Participants With Occurrence of Detectable Dengue Virus (DENV) RiboNucleic Acid (RNA) in Primary DENV Infection
Number of participants with occurrence of detectable DENV RNA in primary DENV infection was a planned analysis.
Time frame: Predose: 24 hour on Day 2; Post dose: 12 hour on Day 1; 36 hour on Day 2; Days 3, 4, 5, 6, 7, 8, 9, 14, 21 and 28
Population: Due to small number of enrolled participants, planned data collection and analysis was not performed and thus no data was reported for this outcome measure.
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were those AE events that occurred at or after the initial administration of study intervention through the last onsite visit.
Time frame: From Day 1 up to the last onsite visit (Day 30)
Population: Safety population included all randomized participants who had taken at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64281802 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
Secondary
Plasma Concentrations of JNJ-64281802
Plasma Concentrations of JNJ-64281802 was assessed. Due to small number of enrolled participants, no summary statistics analysis was performed. Participant wise data were reported for this outcome measure.
Time frame: Predose: 0, 8, 16 hours on Day 1; 24, 32, 40 hours on Day 2; Day 4, Day 5; and Post dose: 4, 12 hours on Day 1; 28, 36 hours on Day 2; 48 hours on Day 3; Day 6, Day 14, Day 21, Day 28
Population: Pharmacokinetic population which included all participants who receive at least 1 dose of study drug and who had at least 1 plasma concentration data value after dosing. Data for this outcome measure was not planned to be collected and analyzed for the placebo arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 1, pre-dose | 5.00 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 1, 4 hr post-dose | 1840 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 1, 8 hr pre-dose | 2380 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 1, 12 hr post-dose | 3210 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 1, 16 hr pre-dose | 3530 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 2, 24 hr pre-dose | 3300 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 2, 28 hr post-dose | 3260 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 2, 32 hr pre-dose | 3840 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 2, 36 hr post-dose | 4240 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 2, 40 hr pre-dose | 4580 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 3, 48 hr post-dose | 4880 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 4, pre-dose | 3790 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 5, pre-dose | 3880 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 6, post-dose | 4270 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 14 post-dose | 1950 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 21 post dose | 1520 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 1: Day 28 post dose | 954 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 1, pre-dose | 5.00 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 1, 4 hr post-dose | 694 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 1, 8 hr pre-dose | 819 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 1, 12 hr post-dose | 1390 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 1, 16 hr pre-dose | 1460 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 2, 24 hr pre-dose | 1720 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 2, 28 hr post-dose | 2430 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 2, 32 hr pre-dose | 2400 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 2, 36 hr post-dose | 3710 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 2, 40 hr pre-dose | 3960 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 3, 48 hr post-dose | 3190 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 4, pre-dose | 1780 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 5, pre-dose | 2130 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 6, post-dose | 2440 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 14 post-dose | 1370 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 21 post dose | 991 nanograms per milliliter |
| JNJ-64281802 | Plasma Concentrations of JNJ-64281802 | Participant 2: Day 28 post dose | 686 nanograms per milliliter |
Secondary
Time to Undetectable Dengue Virus (DENV) RiboNucleic Acid (RNA) in Primary DENV Infection
Time to undetectable DENV RNA in primary DENV infection was a planned analysis.
Time frame: Predose: 24 hour on Day 2; Post dose: 12 hour on Day 1; 36 hour on Day 2; Days 3, 4, 5, 6, 7, 8, 9, 14, 21 and 28
Population: Due to small number of enrolled participants, planned data collection and analysis was not performed and thus no data was reported for this outcome measure.
Secondary
Trough (Pre-dose) Analyte Concentration (Ctrough) of JNJ-64281802
Ctrough is defined as plasma concentration just prior to the beginning or at the end of a dosing interval of JNJ-64281802.
Time frame: Pre-dose on Day 1: 0 hour, 8 hour, 16 hour; pre-dose on Day 2: 24 hour, 32 hour, 40 hour; pre-dose on Day 4 and Day 5
Population: Due to small number of enrolled participants, formal analysis was not performed for the planned PK parameters and thus no data was reported for this outcome measure.