A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Rozanolixizumab Administered Subcutaneously Via Manual Push Versus Syringe Driver to Healthy Participants

Sponsor

UCB Biopharma SRL (Industry)

Overall Status

Completed

CT.gov ID

NCT04828343

Collaborator

(none)

Enrollment

Location

Arms

11.6

Actual Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single subcutaneous (SC) dose of rozanolixizumab administered to healthy participants by manual push (MP) versus (vs) syringe driver.

Condition or Disease	Intervention/Treatment	Phase
Healthy Study Participants	Drug: rozanolixizumab Other: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

This is a participant-blind and investigator-blind study.

Primary Purpose:

Basic Science

Official Title:

A Randomized, Participant-Blind, Investigator-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Rozanolixizumab Administered Subcutaneously Via Manual Push Versus Syringe Driver to Healthy Participants

Actual Study Start Date :

Apr 22, 2021

Actual Primary Completion Date :

Apr 11, 2022

Actual Study Completion Date :

Apr 11, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 <50 kg Study participants randomized to Cohort 1 will receive a single dose of rozanolixizumab (RLZ) or placebo (PBO) subcutaneously administered with a syringe driver.	Drug: rozanolixizumab Study participants will receive a single dose rozanolixizumab subcutaneously administered by manual push or a syringe driver. Other Names: RLZ Other: Placebo Study participants will receive a single dose placebo subcutaneously administered by manual push or a syringe driver. Other Names: PBO
Experimental: Cohort 2 <50 kg Study participants randomized to Cohort 2 will receive a single dose of rozanolixizumab (RLZ) or placebo (PBO) subcutaneously administered by manual push.	Drug: rozanolixizumab Study participants will receive a single dose rozanolixizumab subcutaneously administered by manual push or a syringe driver. Other Names: RLZ Other: Placebo Study participants will receive a single dose placebo subcutaneously administered by manual push or a syringe driver. Other Names: PBO
Experimental: Cohort 3 >=50 kg Study participants randomized to Cohort 3 will receive a single dose of rozanolixizumab (RLZ) or placebo (PBO) subcutaneously administered with a syringe driver.	Drug: rozanolixizumab Study participants will receive a single dose rozanolixizumab subcutaneously administered by manual push or a syringe driver. Other Names: RLZ Other: Placebo Study participants will receive a single dose placebo subcutaneously administered by manual push or a syringe driver. Other Names: PBO
Experimental: Cohort 4 >=50 kg Study participants randomized to Cohort 4 will receive a single dose of rozanolixizumab (RLZ) or placebo (PBO) subcutaneously administered by manual push.	Drug: rozanolixizumab Study participants will receive a single dose rozanolixizumab subcutaneously administered by manual push or a syringe driver. Other Names: RLZ Other: Placebo Study participants will receive a single dose placebo subcutaneously administered by manual push or a syringe driver. Other Names: PBO

Outcome Measures

Primary Outcome Measures

Incidence of treatment-emergent adverse events (TEAEs) [From start of dosing (Day 1) to End of Safety Follow-Up (up to Day 57)]
A TEAE is defined as any adverse event (AE) with a start date/time on or after the dosing of study medication until 8 weeks after dosing of study medication.

Secondary Outcome Measures

Maximum plasma concentration (Cmax) of a single dose rozanolixizumab [Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately at the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after start of infusion, and on Days 7, 10, 13, and 16]
Cmax: Maximum plasma concentration of a single dose rozanolixizumab
Time to maximum plasma concentration (tmax) of a single dose rozanolixizumab [Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately at the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after start of infusion, and on Days 7, 10, 13, and 16]
tmax: Time to maximum plasma concentration of a single dose rozanolixizumab
Area under the plasma concentration-time curve from time zero to time t (AUC0-t) of a single dose rozanolixizumab [Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately at the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after start of infusion, and on Days 7, 10, 13, and 16]
AUC0-t: Area under the plasma concentration-time curve from time zero to time t of a single dose rozanolixizumab
Baseline-corrected area under the Total immunglobulin (Ig) G-time curve [Sampling time points for total IgG will be as follows: 24, 36, 48, 72, and 96 hours after start of infusion, and on Days 7, 10, 13, 16, 19, 22, 29, 43 and 57]
Area under the baseline-corrected total IgG response curve from time 0 to time t
Maximum decrease in total plasma IgG (Rmin) of a single dose rozanolixizumab [Sampling time points for total IgG will be as follows: 24, 36, 48, 72, and 96 hours after start of infusion, and on Days 7, 10, 13, 16, 19, 22, 29, 43 and 57]
Rmin: Maximum decrease in total plasma IgG of a single dose rozanolixizumab
Time to minimum IgG level (tmin) of a single dose rozanolixizumab [Sampling time points for total IgG will be as follows: 24, 36, 48, 72, and 96 hours after start of infusion, and on Days 7, 10, 13, 16, 19, 22, 29, 43 and 57]
tmin: Time to minimum IgG level of a single dose rozanolixizumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Study participant must be 18 to 65 years of age, inclusive
Study participants who are overtly healthy in the opinion of the investigator as determined by medical evaluation including medical history, a general clinical examination, including physical examination and laboratory tests, and cardiac monitoring
Study participant has blood pressure (BP) and pulse within normal range in a supine position after 5 minutes of rest (systolic BP: 90 to 140 mmHg, diastolic BP: 50 to 90 mmHg, pulse: 40 to 90 beats per minute (bpm))
Study participant has clinical laboratory test results within the reference ranges of the testing laboratory or not clinically significant if outside the specified ranges, in the opinion of the investigator
Study participant's electrocardiogram (ECG) is considered "normal" or "abnormal but clinically nonsignificant" (as interpreted by the investigator)
Study participants may be male or female
Participant has a body mass index of 18 to 32 kg/m^2, with a minimum body weight of 35 kg

Exclusion Criteria:

History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders. Has active neoplastic disease or history of neoplastic disease within the previous 5 years of entry in the clinical study (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitively treated with standard of care approaches). Has a history of a major organ transplant or hematopoietic stem cell/marrow transplant
Symptomatic herpes zoster within 3 months prior to Screening
Allergies to humanized monoclonal antibodies
Female who is pregnant or lactating
Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions
Evidence of active or latent tuberculosis (TB) as documented by medical history and examination
Predicted inability to comply with being free of caffeine and ethanol from 72 hours prior to clinic admission and during the In-Clinic Period of the study
Known hypersensitivity to oral paracetamol (acetaminophen)
History of known inflammatory bowel disease, active diverticular disease, or a history of confirmed duodenal, gastric, or esophageal ulceration in the previous 6 months
History of hyperprolinemia, since L-proline is a constituent of rozanolixizumab.
Twelve-lead ECG with abnormalities considered to be clinically significant upon medical review
Renal impairment, defined as a creatinine concentration in serum of ≥1.4 mg/dL (≥123 μmol/L) for female participants and ≥1.5 mg/dL (≥132 μmol/L) for male participants
Known viral hepatitis (B and C) or human immunodeficiency virus 1/2 antibodies or has a past medical history or family history of primary immunodeficiency or antibodies to human immunodeficiency virus type 1 and/or type 2 at Screening
Participant has a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reverse transcriptase-polymerase chain reaction on admission to the unit
Participant has clinical signs and symptoms consistent with SARS-CoV-2 (eg, fever, dry cough, dyspnea, sore throat, fatigue) or confirmed infection by appropriate laboratory test within the previous 14 days prior to Screening or on admission
Participant has active infection or is symptomatic with SARS-CoV-2 or is currently in quarantine (has been in contact with a SARS-CoV-2 positive individual in the last 14 days)
Participant has had a severe course of SARS-CoV-2 (eg, requiring extracorporeal membrane oxygenation, mechanical ventilation, or hospitalization)
Past or intended use of over-the-counter or prescription medication (including herbal medications) within 14 days prior to dosing until Day 57
Live vaccine(s) within 8 weeks prior to Screening or plans to receive such vaccines during the study or is within a dosing cycle to receive a second dose of a coronavirus disease-19 (COVID-19) vaccine, or within 2 weeks of having received a COVID-19 vaccine
Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing
Exposure to more than 3 new chemical entities within 12 months prior to dosing
Has previously been assigned to treatment in a clinical study of rozanolixizumab
Participated in another study of an investigational medicinal product (IMP) (or a medical device) within the previous 90 days or 5 half-lives prior to Day -1 (whichever is longer) or is currently participating in another study of an IMP (or a medical device)
Immunoglobulin G <7g/L or >16g/L at the Screening Visit
Participant is splenectomized or has had an active clinically significant infection within the last 6 weeks
Donated or lost >500 mL of blood or blood products in the 3 months preceding the start of dosing or plans to donate blood during the clinical study
Employee or direct relative of an employee of the contract research organization (CRO) or UCB
History of alcohol and/or drug abuse up to 12 months before Screening
Smoked on average >5 cigarettes/day (or equivalent) during the last 3 months and is not able to stop smoking during the In-Clinic Period
Excessive consumption of beverages or food containing xanthine bases (including caffeinated drinks, coffee, chocolate, etc.), equating to >400 mg caffeine per day