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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Daratumumab; Drug: rHuPH20; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daratumumab; 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; Single SC dose of daratumumab will be administered in each of 8 dose cohorts.; Other Names: JNJ-54767414; Drug: rHuPH20; Participants in Cohort 8 will receive single SC dose of rHuPH20 as a part of daratumumab formulation.
Placebo Comparator: Placebo; Participants will receive placebo as a single SC dose in each of first 7 cohorts.	Drug: Placebo; Placebo liquid will be administered as SC dose in each of first 7 dose cohorts.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2017
• Primary Completion (Actual): August 27, 2019
• Study Completion (Actual): August 27, 2019

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 25, 2017

Study Record Updates

• Last Update Posted (Actual): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 4, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: CR108356; 54767414EDI1001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No