A Study of JNJ-77474462 in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetics (PK) of JNJ-77474462 after single subcutaneous (SC) or intravenous (IV) administrations and the effect of formulation concentrations on PK of JNJ-77474462 in healthy participants.

Official Title
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A Phase 1 Study to Investigate the Pharmacokinetics and Pharmacodynamics of JNJ-77474462 in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: JNJ-77474462
* Drug: Anakinra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Otherwise healthy on the basis of physical examination, medical history, vital signs, and 12 lead electrocardiogram (ECG) performed at screening. Any abnormalities must be considered not clinically significant and this determination must be recorded in the participant's source documents and initialed by the investigator Otherwise healthy on the basis of clinical laboratory tests performed at screening and Day 1. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator A woman of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta hCG) at screening and a negative urine pregnancy test on Day -1 A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 90 days post study intervention administration 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: History of any clinically significant medical illness or medical disorders the investigator considers should exclude the participant, including (but not limited to), neuromuscular, hematological disease, immune deficiency state, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease Has a history of malignancy before screening. Exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix, or a malignancy which is considered cured with minimal risk of recurrence Has or has had a serious infection (example: sepsis, pneumonia, or pyelonephritis), or have been hospitalized or received intravenous (IV) antibiotics for a serious infection during the 4 months prior to the screening visit Is currently enrolled in an investigational study or has received an investigational intervention (including investigational vaccines or devices) 5 half-lives or 8 weeks prior to screening (whichever is longer) Has received prescription medications within 2 weeks prior to first study intervention administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: JNJ-77474462 SC (Wave 1)<br>Participants will receive single dose of JNJ-77474462 subcutaneously (SC). | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Experimental: Cohort B: JNJ-77474462 SC (Wave 1)<br>Participants will receive single dose of JNJ-77474462 SC. | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Experimental: Cohort C: JNJ-77474462 SC (Wave 1)<br>Participants will receive single dose of JNJ-77474462 SC. | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Experimental: Cohort D: JNJ-77474462 SC (Wave 1)<br>Participants will receive single dose of JNJ-77474462 SC. | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Experimental: Cohort E: JNJ-77474462 IV (Wave 1)<br>Participants will receive single dose of JNJ-77474462 intravenously (IV). | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Experimental: Cohort F: JNJ-77474462 SC (Wave 2)<br>Participants will receive single dose of JNJ-77474462 SC. | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Experimental: Cohort G: JNJ-77474462 SC (Wave 2)<br>Participants will receive single dose of JNJ-77474462 SC. | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Experimental: Cohort H: JNJ-77474462 IV (Wave 2)<br>Participants will receive single dose of JNJ-77474462 IV. | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Experimental: Cohort I: JNJ-77474462 IV (Wave 2)<br>Participants will receive single dose of JNJ-77474462 IV. | Drug: JNJ-77474462<br>* Participants will receive JNJ-77474462 as a liquid formulation in Cohort A, B, C, D, F and G (SC injection) and in Cohort E, H and I (IV infusion).<br>* Other names: Bermekimab;|
| Active Comparator: Cohort J: Anakinra SC<br>Participants will receive a SC injection of anakinra once daily for 3 days. | Drug: Anakinra<br>* Participants will receive a SC injection of anakinra 100 mg once daily for 3 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of JNJ-77474462 | Cmax is the maximum observed plasma concentration. | Up to Week 12 | 
| Area Under the Plasma Concentration Versus Time Curve from Time Zero to Infinity with Extrapolation of the Terminal Phase (AUC[0-infinity]) of JNJ-77474462 | AUC(0-infinity) is defined as area under the plasma concentration versus time curve from time zero to infinity with extrapolation of the terminal phase of JNJ-77474462. | Up to Week 12 | 
| Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Time Corresponding to the Last Quantifiable Concentration (AUC[0-last]) of JNJ-77474462 | AUC(0-last) is defined as area under the plasma concentration versus time curve from time zero to the time corresponding to the last quantifiable concentration of JNJ-77474462. | Up to Week 12 | 
| Terminal Half-Life (T1/2) of JNJ-77474462 | T1/2 is defined as the time measured for the plasma concentration to decrease by 1 half of its original concentration. | Up to Week 12 | 
| Absolute Subcutaneous (SC) Bioavailability (F%) | (F%) is defined as absolute SC bioavailability to be calculated using the following equation: AUC(0-infinity) SC/mean AUC(0-infinity) IV * 100 percent (%). | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Treatment-emergent Adverse Events (TEAE) | An 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 are defined as adverse events (AEs) with onset or worsening on or after date of first dose of study treatment. | Up to Week 12 | 
| Percentage of Participants with Serious Adverse Events (SAE) | A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Up to Week 12 | 
| Number of Participants with Clinically Significant Changes in Vital Signs | Number of participants with clinically significant changes in vital signs (including body temperature, resting [supine] pulse/heart rate, respiratory rate and blood pressure) will be reported. | Up to Week 12 | 
| Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) | Number of participants with clinically significant changes ECG will be reported. | Up to Week 12 | 
| Number of Participants with Clinically Significant Changes in Laboratory Findings | Number of participants with clinically significant changes in laboratory findings (that is, hematology, clinical chemistry, urinalysis) will be reported. | Up to Week 12 | 
| Number of Participants with Anti-JNJ-77474462 Antibodies | Number of participants with anti-drug antibodies to JNJ-77474462 will be reported. | Up to Week 12 |