A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-54767414 (Daratumumab) in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of daratumumab following a single subcutaneous (SC) administration in healthy participants and to determine whether premedication with corticosteroids is required to improve the tolerability of SC administration of daratumumab in healthy participants.

Official Title
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A Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-54767414 (Daratumumab) in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: Daratumumab
* Drug: Placebo
* Drug: rHuPH20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have a body weight in the range of 50 to 100 kilogram (kg), inclusive, and have a body mass index (BMI) of 19 to 30 kilogram per meter square (kg/m^2), inclusive, at screening and Day -1 Must be otherwise healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and Day -1 Must be otherwise healthy on the basis of clinical laboratory tests performed at screening and Day -1 A woman must not be of childbearing potential Must be a non-smoker or tobacco user or 3 months prior to screening Exclusion Criteria: Pregnant or breastfeeding while enrolled in this study or within 20 weeks after the dose of study treatment History of or currently has any clinically significant medical illness or medical disorders the investigator considers significant, including, but not limited to immune deficiency state, liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances Has a history of malignancy before screening. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or a malignancy which is considered cured with minimal risk of recurrence Active acute or chronic infection (including chronic recurrent or invasive candidiasis) or diagnosed latent infection Has had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening and/or plan to receive a BCG vaccine within 12 months after the administration of study treatment Has experienced a recent single dermatomal herpes zoster eruption within the past 6 months Has a history of multi-dermatomal herpes zoster or central nervous system (CNS) zoster within the past 5 years Has received prescription medications within 14 days prior to study treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daratumumab<br>Participants will receive a single subcutaneous (SC) dose of daratumumab in each of first 7 dose cohorts. Doses will be escalated based on review of pharmacokinetic, pharmacodynamic, and safety data of previous cohort. Participants in Cohort 8 will receive single SC daratumumab formulation containing recombinant human hyaluronidase (rHuPH20). | Drug: Daratumumab<br>* Single SC dose of daratumumab will be administered in each of 8 dose cohorts.<br>* Other names: JNJ-54767414;Drug: rHuPH20<br>* Participants in Cohort 8 will receive single SC dose of rHuPH20 as a part of daratumumab formulation.<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo as a single SC dose in each of first 7 cohorts. | Drug: Placebo<br>* Placebo liquid will be administered as SC dose in each of first 7 dose cohorts.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Treatment-Emergent Adverse Event (TEAEs) by Severity Through Day 141 Versus Placebo | The safety and tolerability of daratumumab following a single subcutaneous (SC) administration in healthy participants will be assessed. | Up to Day 141 | 
| Proportion of Participants With TEAEs by Serious Adverse Events (SAEs) Through Day 141 Versus Placebo | The safety and tolerability of daratumumab following a single subcutaneous (SC) administration in healthy participants will be assessed. | Up to Day 141 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Cmax is the maximum observed plasma concentration. | Day 1 predose through Day 141 | 
| Time to the Maximum Observed Plasma Concentration (Tmax) | Tmax is defined as actual sampling time to reach maximum observed plasma concentration. | Day 1 predose through Day 141 | 
| Area Under the Plasma Concentration-time Curve From Time Zero to the Time Corresponding to the Last Quantifiable Serum Concentration (AUC [0-last]) | AUC (0-last) is the area under the plasma concentration-time curve from time zero to the time corresponding to the last quantifiable serum concentration. | Day 1 predose through Day 141 | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUC[0- infinity]) | AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinity with extrapolation of the terminal phase, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant. | Day 1 predose through Day 141 | 
| Number of Participants With Anti-daratumumab Antibodies | Number of participants who test positive for anti-daratumumab antibodies will be reported. | Day 1 predose through Day 141 | 
| Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies | Number of participants who test positive for anti-rHuPH20 antibodies will be reported. | Day 1 predose through Day 141 | 
| Percentage of CD38 Expression Levels and CD38 Expressing Cell Counts Measured by Flow Cytometry | The cluster of differentiation (CD) 38 expression levels and CD38 expressing cell counts, as measured by flow cytometry, will be summarized. | Day 1 predose through Day 141 |