Clinical trial NCT04973566: A Study of Nipocalimab With Co-administration of Etanercept or Hydroxychloroquine in Healthy Participants
Official title: A Phase 1, Open-Label Study to Investigate Drug-Drug Interaction (DDI) Potential of Nipocalimab With Coadministration of Etanercept or Hydroxychloroquine in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-07-22
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 is a single-sequence, 2-period study and Part 2 is a randomized, 2-cohort (Cohort 1 and Cohort 2), parallel study.
Primary purpose: OTHER

Brief summary: The primary purpose of this study is to assess the effect of nipocalimab on the pharmacokinetic (PK) of etanercept (Part 1); and to assess the effect of hydroxychloroquine (HCQ) on total serum immunoglobin G (IgG) reduction by nipocalimab (Part 2) in healthy participants.


Eligibility criteria: Inclusion Criteria:

* Healthy based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. If there are any abnormalities, they must be consistent with the underlying illness in the study population or considered not clinically relevant and this determination must be recorded in the participant's source documents and initialed by the investigator
* Healthy on the basis of clinical laboratory tests performed at screening (including immunoglobulin \[Ig\]G) and at admission to the study site. If the results of the serum chemistry panel, liver 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
* Good venous access in both arms
* Participants must have heart rate of at least 50 beats per minute
* Participant is considered eligible according to the following tuberculosis (TB) screening criteria (for Part 1 only): a) have no history of latent or active TB before screening; b) have no signs or symptoms suggestive of active TB upon medical history and/or physical examination; c) have had no recent close contact with a person with active TB; d) have a negative QuantiFERON-TB test result within 28 days prior to the administration of study intervention
* Part 1: Body mass index (BMI) greater than or equal to (\>=) 18.0 to less than or equal to (\<=) 30.0 kilogram (kg)/meter (m)\^2 (inclusive), and body weight \>= 50 to \<= 110.0 kg (inclusive) at the screening visit and on Day -1; Part 2: BMI \>= 18.0 to \<= 30.0 kg/m\^2 (inclusive), and body weight \>= 61.5 to \<= 110.0 kg (inclusive) at the screening visit and on Day -1
* A female participant must have a negative serum (beta-human chorionic gonadotropin) test at screening and a urine pregnancy test at Day -1 prior to administration of study intervention
* It is recommended that participants are up to date on age-appropriate vaccinations prior to screening per routine local medical guidelines. For study participants who received locally-approved (and including emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccines recently prior to study entry, applicable local vaccine labeling, guidelines, and standards of care for participants receiving immune-targeted therapy should be followed when determining an appropriate interval between vaccination and study enrollment

Exclusion Criteria:

* Has a history of liver or renal insufficiency; cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
* Has a history of retinal and macular disease (only for Part 2)
* Has shown a previous severe immediate hypersensitivity reaction response, including anaphylaxis, to therapeutic proteins (example, monoclonal antibody \[mAbs\])
* Has serum albumin levels \< 30 grams/Liter (g/L) at screening and Day -1
* Has a history of myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks prior to screening

Primary outcomes:
measure: Part 1: Serum Etanercept Concentration
timeFrame: Up to Day 99
measure: Part 1: Ratio of Area Under the Concentration-time Curve (AUCR) of Etanercept
timeFrame: Up to Day 99
measure: Part 1: Area Under the Concentration-time Curve of Etanercept from Time Zero to Time of Last Observed Quantifiable Concentration (AUC [0-Last])
timeFrame: Up to Day 99
measure: Part 1: Area Under the Concentration-time Curve of Etanercept from Time Zero to Infinite time (AUC [0-Infinity])
timeFrame: Up to Day 99
measure: Part 1: Maximum Observed Concentration (Cmax) of Etanercept
timeFrame: Up to Day 99
measure: Part 1: Ratio of Maximum Observed Concentration (CmaxR) of Etanercept
timeFrame: Up to Day 99
measure: Part 1: Time to Reach the Last Observed Measurable Analyte Concentration (Tlast) of Etanercept
timeFrame: Up to Day 99
measure: Part 1: Time to Reach the Maximum Observed Concentration (Tmax) of Etanercept
timeFrame: Up to Day 99
measure: Part 1: Elimination Half-life (t1/2) of Etanercept
timeFrame: Up to Day 99
measure: Part 1: Total Apparent Clearance (CL/F) of Etanercept
timeFrame: Up to Day 99
measure: Part 1: Apparent Volume of Distribution (Vdz/F) of Etanercept
timeFrame: Up to Day 99
measure: Part 2: Change from Baseline in Total Serum Immunoglobulin (Ig) Levels
timeFrame: Baseline up to Day 50
Secondary outcomes:
measure: Part 1: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 4 months
measure: Part 1: Number of Participants with Abnormalities in Physical Examinations
timeFrame: Up to 4 months
measure: Part 1: Number of Participants with Abnormalities in Vital Sign Measurements
timeFrame: Up to 4 months
measure: Part 1: Number of Participants with Abnormalities in Clinical Laboratory Tests
timeFrame: Up to 4 months
measure: Parts 1 and 2: Serum Nipocalimab Concentrations
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Part 1: AUCR of Nipocalimab
timeFrame: Up to Day 99
measure: Parts 1 and 2: AUC (0-Last) of Nipocalimab
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Parts 1 and 2: AUC (0-Infinity) of Nipocalimab
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Parts 1 and 2: Cmax of Nipocalimab
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Part 1: CmaxR of Nipocalimab
timeFrame: Up to Day 99
measure: Parts 1 and 2: Tlast of Nipocalimab
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Parts 1 and 2: Tmax of Nipocalimab
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Parts 1 and 2: t1/2 of Nipocalimab
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Parts 1 and 2: Total Systemic Clearance of Nipocalimab (CL)
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Parts 1 and 2: Volume of Distribution (Vdz) of Nipocalimab
timeFrame: Up to Day 99 (Part 1); up to Day 50 (Part 2)
measure: Part 1: Number of Participants with Antibodies to Nipocalimab
timeFrame: Up to Day 99
measure: Part 2: Serum Lipid and Albumin Levels
timeFrame: Up to Day 50
measure: Part 2: Number of Participants with Receptor Occupancy (RO) Levels of Nipocalimab
timeFrame: Up to Day 50
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRA Health Sciences
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: