A Study of Nipocalimab With Co-administration of Etanercept or Hydroxychloroquine in Healthy Participants

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04973566
• Other study ID #: CR109053
• Secondary ID: 2021-001656-3380
• Status: Completed
• Phase: Phase 1
• Start date: August 31, 2021
• Est. completion date: May 27, 2022

Study information

• Verified date: June 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: May 27, 2022
• Est. primary completion date: May 27, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Nipocalimab
Nipocalimab will be administered as an IV infusion.
• Etanercept
Etanercept will be administered subcutaneously.
• Hydroxychloroquine
HCQ will be administered orally.

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Serum Etanercept Concentration	Serum etanercept concentration will be reported.	Up to Day 99
Primary	Part 1: Ratio of Area Under the Concentration-time Curve (AUCR) of Etanercept	AUCR is defined as the ratio of area under the concentration-time curve.	Up to Day 99
Primary	Part 1: Area Under the Concentration-time Curve of Etanercept from Time Zero to Time of Last Observed Quantifiable Concentration (AUC [0-Last])	AUC (0-last) is defined as area under the concentration-time curve of etanercept from time zero to time of last observed quantifiable concentration.	Up to Day 99
Primary	Part 1: Area Under the Concentration-time Curve of Etanercept from Time Zero to Infinite time (AUC [0-Infinity])	AUC (0-Infinity) is defined as area under the concentration-time curve of etanercept from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z) where AUC (0-last) is area under the concentration-time curve of etanercept from time zero to time of last observed quantifiable concentration and C(last) is the last observed quantifiable concentration, and lambda(z) is apparent terminal elimination rate constant.	Up to Day 99
Primary	Part 1: Maximum Observed Concentration (Cmax) of Etanercept	Cmax is defined as maximum observed concentration of etanercept.	Up to Day 99
Primary	Part 1: Ratio of Maximum Observed Concentration (CmaxR) of Etanercept	CmaxR is defined as ratio of maximum observed concentration of etanercept.	Up to Day 99
Primary	Part 1: Time to Reach the Last Observed Measurable Analyte Concentration (Tlast) of Etanercept	Tlast is defined as time to reach the last observed measurable analyte concentration of etanercept.	Up to Day 99
Primary	Part 1: Time to Reach the Maximum Observed Concentration (Tmax) of Etanercept	Tmax is defined as time to reach the maximum observed concentration of etanercept.	Up to Day 99
Primary	Part 1: Elimination Half-life (t1/2) of Etanercept	t1/2 is defined as elimination half-life associated with the terminal slope lambda(z) of the semilogarithmic drug concentration-time curve, calculated as 0.693/ lambda(z).	Up to Day 99
Primary	Part 1: Total Apparent Clearance (CL/F) of Etanercept	CL/F is total apparent clearance of etanercept following subcutaneous (SC) administration, calculated as dose/AUC (0-infinity).	Up to Day 99
Primary	Part 1: Apparent Volume of Distribution (Vdz/F) of Etanercept	Vdz/F is defined as apparent volume of distribution based on the terminal phase after an SC dose, calculated as dose/lambda(z)*AUC(0-infinity).	Up to Day 99
Primary	Part 2: Change from Baseline in Total Serum Immunoglobulin (Ig) Levels	Change from baseline in total serum Ig levels (serum IgG and IgG subtypes) through Day 50 will be reported.	Baseline up to Day 50
Secondary	Part 1: Number of Participants with Adverse Events (AEs)	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.	Up to 4 months
Secondary	Part 1: Number of Participants with Abnormalities in Physical Examinations	Number of participants with abnormalities in physical examinations (full and brief) will be reported. Full physical examinations will include a review of the following body systems: general appearance; thorough skin and oral mucosa evaluation; eyes, ears, nose, and throat; cardiovascular; respiratory; abdomen; peripheral pulsation; lymph nodes; neurologic; musculoskeletal; head, neck, and thyroid. A brief physical examination includes review of the following body systems: general appearance, thorough skin (including site of the injection) and oral mucosa, abdomen, respiratory, cardiovascular, any abnormalities noted on previous examinations.	Up to 4 months
Secondary	Part 1: Number of Participants with Abnormalities in Vital Sign Measurements	Number of participants with abnormalities in vital sign measurements (body temperature [temporal artery measurement], pulse/heart rate, respiratory rate, blood pressure) will be reported.	Up to 4 months
Secondary	Part 1: Number of Participants with Abnormalities in Clinical Laboratory Tests	Number of participants with abnormalities in clinical laboratory tests (serum chemistry, liver panel, hematology, and urinalysis) will be reported.	Up to 4 months
Secondary	Parts 1 and 2: Serum Nipocalimab Concentrations	Serum nipocalimab concentrations will be reported.	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Part 1: AUCR of Nipocalimab	AUCR is defined as the ratio of area under the concentration-time curve.	Up to Day 99
Secondary	Parts 1 and 2: AUC (0-Last) of Nipocalimab	AUC (0-last) is defined as area under the concentration-time curve of nipocalimab from time zero to time of last observed quantifiable concentration.	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Parts 1 and 2: AUC (0-Infinity) of Nipocalimab	AUC (0-Infinity) is defined as area under the concentration-time curve of nipocalimab from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z) where AUC (0-last) is area under the concentration-time curve of nipocalimab from time zero to time of last observed quantifiable concentration and C(last) is the last observed quantifiable concentration, and lambda(z) is apparent terminal elimination rate constant.	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Parts 1 and 2: Cmax of Nipocalimab	Cmax is defined as maximum observed concentration of nipocalimab.	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Part 1: CmaxR of Nipocalimab	CmaxR is defined as ratio of maximum observed concentration of nipocalimab.	Up to Day 99
Secondary	Parts 1 and 2: Tlast of Nipocalimab	Tlast is defined as time to reach the last observed measurable analyte concentration of nipocalimab.	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Parts 1 and 2: Tmax of Nipocalimab	Tmax is defined as time to reach the maximum observed concentration of nipocalimab.	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Parts 1 and 2: t1/2 of Nipocalimab	t1/2 is defined as elimination half-life associated with the terminal slope lambda(z) of the semilogarithmic drug concentration-time curve, calculated as 0.693/ lambda(z).	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Parts 1 and 2: Total Systemic Clearance of Nipocalimab (CL)	CL is defined as total systemic clearance of nipocalimab following an intravenous (IV) administration, calculated as dose/AUC (0-infinity).	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Parts 1 and 2: Volume of Distribution (Vdz) of Nipocalimab	Vdz is defined as volume of distribution, based on the terminal phase after an IV dose, calculated as dose/lambda(z)*AUC (0-infinity).	Up to Day 99 (Part 1); up to Day 50 (Part 2)
Secondary	Part 1: Number of Participants with Antibodies to Nipocalimab	Number of participants with antibodies to nipocalimab will be reported.	Up to Day 99
Secondary	Part 2: Serum Lipid and Albumin Levels	Participants serum lipid and albumin levels will be reported.	Up to Day 50
Secondary	Part 2: Number of Participants with Receptor Occupancy (RO) Levels of Nipocalimab	Number of Participants with RO levels (example, neonatal Fc receptor [FcRn] RO in circulating monocytes) of nipocalimab will be reported.	Up to Day 50