A Study of JNJ-64281802 for the Prevention of Dengue Infection

Phase 2TerminatedNCT05201794

Janssen Research & Development, LLC1,595 enrolled

Overview

The purpose of this study is to evaluate the prophylactic effect of JNJ-64281802 with respect to the prevention of laboratory-confirmed dengue virus (DENV) infection up to the last day of dosing among participants who have no evidence of current DENV infection at baseline.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

1,595

Conditions

Dengue

Interventions

JNJ-64281802DRUG

JNJ-64281802 tablets will be administered orally as per the defined regimens.

PlaceboDRUG

Matching placebo for each dose level as tablet will be administered orally.

Eligibility

Sex: ALLMin age: 16 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy on the basis of physical examination, medical history, and vital signs performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities to be not clinically relevant. This determination must be recorded in the participant's source documents * Must have a body mass index (BMI, weight in kilogram \[kg\] divided by the square of height in meters) between 18.0 and 35.0 kilograms per meter square (kg/m\^2) inclusive, and a body weight of greater than or equal to (\>=) 40.0 kg at screening * A woman must have a negative highly sensitive urine pregnancy test at screening * A male participant must agree not to donate sperm for the purpose of reproduction during the study and for \>= 90 days after receiving the last dose of study intervention * Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study Exclusion Criteria: * Having any dengue virus (DENV)-associated clinical signs and symptoms * Known allergies, hypersensitivity, or intolerance to JNJ-64281802 or its excipients * Any clinically relevant skin disease (as assessed by the investigator) in the past 3 months such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticaria * Reduced immune function to be: (a) Known or suspected congenital or acquired immunodeficiency; or (b) receipt of immunomodulation therapy within the last 6 months (such as anticancer chemotherapy or radiation therapy) * Received an investigational intervention (including investigational vaccines other than a corona virus disease 2019 \[COVID-19\] vaccine) or used an invasive investigational medical device within 3 months before the planned first dose of study intervention or received an investigational biologic product within 3 months prior to enrollment or 5 half-lives, whichever is longer, before the planned first dose of study intervention, or is currently enrolled in an investigational study

Locations (38)

Outcomes

Primary Outcomes

Number of Participants With Laboratory-confirmed Dengue Virus (DENV) Infection Between Baseline and the Last Day of Dosing + 1 Day Among Household Contacts (HHC) Participants With No Evidence of DENV Infection at Baseline

Number of participants with DENV infection between baseline and the last day of dosing + 1 day among HHC participants with no evidence of DENV infection at baseline were reported. Presence of a laboratory-confirmed DENV infection was defined as a positive DENV ribonucleic acid (RNA) (assessed using a validated quantitative DENV reverse transcription polymerase chain reaction \[RT-PCR\]) or DENV non-structural protein 1 (NS1); assessed by enzyme-linked immunosorbent assay (ELISA) test result. A sample was considered positive for DENV RNA when the result was 'target detected' (when the result was above the limit of detection of the polymerase chain reaction \[PCR\] assay) or a sample was considered DENV NS1 positive if the qualitative DENV NS1 result was positive (quantitative DENV NS1 result greater than or equal to \[\>=\] 11 relative units per milliliter \[RU/mL\]).

Time frame: Baseline (DB prophylactic Day 1) up to last day of dosing + 1 day (up to DB prophylactic Day 29)

Secondary Outcomes

Number of Participants With Laboratory-confirmed Symptomatic DENV Infection Between Baseline and the Last Day of Dosing + 1 Day Among All HHC Participants (With or Without Evidence of DENV Infection at Baseline)

Number of participants with laboratory-confirmed symptomatic DENV infection between baseline and last day of dosing + 1 day among all HHC participants (with/without evidence of DENV infection at baseline) were reported. Laboratory confirmed symptomatic DENV infection was defined as having at least 2 solicited systemic adverse events (AEs; retro-orbital pain, fever, arthralgia, headache, myalgia, rash, abdominal pain, nausea, fatigue, loss of appetite, vomiting, and diarrhea) of which at least 1 was a most common dengue symptom (retro-orbital pain, fever, arthralgia, headache, myalgia, rash), lasted for \>=1 day and occurred within +/-2 days time window around positive PCR or NS1 test, between baseline and last day of dosing. Sample was considered positive for DENV RNA when result was 'target detected' (when result was above the limit of detection of PCR assay) or sample considered DENV NS1 positive if qualitative DENV NS1 result was positive (quantitative DENV NS1 result \>=11 RU/mL).

Data from ClinicalTrials.gov

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Universidade Federal De Minas Gerais - Hospital das Clínicas

Belo Horizonte, Brazil

HUJM - UFMT - Hospital Universitário Júlio Müller - Universidade Federal do Mato Grosso

Cuiabá, Brazil

Hospital e Maternidade Sao Joao de Deus

Laranjeiras do Sul, Brazil

Fundacao De Medicina Tropical Doutor Heitor Vieira Dourado

Manaus, Brazil

Fundacao Universidade Federal de Mato Grosso do Sul

Mato Grosso Do Sul, Brazil

Policlínica Regional Dr Sérgio Arouca

Niterói, Brazil

UPA Unidade de Pronto Atendimento Mário Monteiro

Niterói, Brazil

Instituto de Pesquisas em Patologias Tropicais de Rondônia - IPEPATRO

Porto Velho, Brazil

Centro Bangu - Centro Municipal de Saude Waldyr Franco

Rio de Janeiro, Brazil

Fundacao Oswaldo Cruz Instituto Nacional de Infectologia Evandro Chagas

Rio de Janeiro, Brazil

...and 28 more locations

Time frame: Baseline (DB prophylactic Day 1) up to last day of dosing + 1 day (up to DB prophylactic Day 29)

Number of Participants With Laboratory-confirmed Symptomatic DENV Infection Between Baseline and the Last Day of Dosing + 1 Day Among HHC Participants With No Evidence of DENV Infection at Baseline

Number of participants with laboratory-confirmed symptomatic DENV infection between baseline and last day of dosing + 1 day among HHC participants with no evidence of DENV infection at baseline were reported. Laboratory confirmed symptomatic DENV infection was defined as having at least 2 solicited systemic AEs (retro-orbital pain, fever, arthralgia, headache, myalgia, rash, abdominal pain, nausea, fatigue, loss of appetite, vomiting, and diarrhea) of which at least 1 was a most common dengue symptom (retro-orbital pain, fever, arthralgia, headache, myalgia, and rash), lasted for \>=1 day and occurred within a +/-2 days time window around the positive PCR or NS1 test, between baseline and the last day of dosing. A sample was considered positive for DENV RNA when the result was 'target detected' (when result was above the limit of detection of PCR assay) or sample was considered DENV NS1 positive if the qualitative DENV NS1 result was positive (quantitative DENV NS1 result \>=11 RU/mL).

Time frame: Baseline (DB prophylactic Day 1) up to last day of dosing + 1 day (up to DB prophylactic Day 29)

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Serious AE was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE occurring at or after initial administration of study intervention until the last study-related activity, or until the participant had been deemed lost to follow-up after demonstration of due diligence of follow up efforts. TEAEs included both serious and non-serious adverse events.

Time frame: DB prophylactic phase: From start of study treatment (Day 1) up to visit Day 50, considering the long half-life (~10 days) of the study intervention; Follow-up phase: From visit Day 50 up to Day 90

Number of Participants With Treatment-emergent (TE) Worst Grade (Grade 3 or 4) Abnormalities in Vital Signs

Vital signs: pulse and blood pressure (systolic blood pressure\[SBP\]/diastolic blood pressure\[DBP\]). Abnormality grades determined per Division of Acquired Immunodeficiency Syndrome (DAIDS) for grading severity of adult and pediatric AEs: SBP(millimeters of mercury\[mmHg\]):Hypertension:Grade (G)1(mild):141-150, G2(moderate):greater than (\>)150-155, G3(severe):\>155; SBP(mmHg):Hypotension:G1(mild):85-89, G2(moderate):80 to less than (\<)85, G3(severe):\<80; DPB(mmHg):Hypertension:G1(mild):91-95, G2(moderate):\>95-100, G3(severe):\>100; Pulse(beats per minutes\[bpm\]):Tachycardia: G1(mild):\>100-115, G2(moderate):\>115-130, G3(severe):\>130; Pulse(bpm):Bradycardia:G1(mild):50-54, G2(moderate):\<50-45, G3(severe):\<45. Any abnormality occurring at/after initial administration of study intervention until last study-related activity, or participant had been deemed lost to follow-up after demonstration of due diligence of follow up efforts was considered TE. Worst TE toxicity grade=highest grade reached.

Time frame: From start of drug administration (DB prophylactic Day 1) up to Day 50

Number of Participants With Treatment-emergent Abnormalities in Electrocardiogram (ECG) Parameters

ECG variables: heart rate (HR), PR interval, RR interval, QRS interval, QT interval, and corrected QT (QTc) interval using both following correction methods: QT corrected according to Bazett's formula (QTcB), QT corrected according to Fridericia's formula (QTcF). Abnormalities were categorized as low or high. HR (bpm): low: \< 45, high: \>=120; PR Interval (milliseconds \[ms\]): low: \<110, high: \>=220; QRS interval (ms): high: \>=120; QTcB and QTcF (ms): Borderline prolonged QT: 450\< QTc \<=480, 480 \<QTc \<=500, QTc \>500. Any abnormality occurring at or after initial administration of study intervention until last study-related activity, or participant had been deemed lost to follow-up after demonstration of due diligence of follow up efforts was considered treatment emergent.

Time frame: Day 28

Number of Participants With Treatment-emergent Worst Grade (Grade 3 or 4) Abnormalities in Laboratory Parameters

Number of participants with treatment-emergent worst grade (Grade 3 or 4) abnormalities in laboratory parameters were reported. Laboratory assessments included clinical chemistry, hematology and urinalysis. Abnormality criterions were based on DAIDS: Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening. Any abnormality occurring at or after initial administration of study intervention until the last study-related activity, or until the participant had been deemed lost to follow-up after demonstration of due diligence of follow up efforts was considered treatment emergent.

Time frame: From start of drug administration (DB prophylactic Day 1) up to Day 50

Number of Participants With Clinically Significant Abnormalities in Physical Examinations

Number of participants with abnormalities in physical examination parameters (head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological) were reported based on investigator's discretion.

Time frame: Day 50

Plasma Concentrations of JNJ-64281802

Plasma concentrations of JNJ-64281802 were reported. Plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.

Time frame: Pre-dose on Day 1; post-dose on Days 3, 5,9, 13, 21, and 28 ; Days 40, 50, and 90