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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Study Participants

Intervention / Treatment
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* Drug: rozanolixizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) | 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. | From start of dosing (Day 1) to End of Safety Follow-Up (up to Day 57) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of a single dose rozanolixizumab | Cmax: Maximum plasma concentration 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 | 
| Time to maximum plasma concentration (tmax) of a single dose rozanolixizumab | tmax: Time to maximum plasma concentration 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 | 
| Area under the plasma concentration-time curve from time zero to time t (AUC0-t) of a single dose rozanolixizumab | AUC0-t: Area under the plasma concentration-time curve from time zero to time 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 | 
| Baseline-corrected area under the Total immunglobulin (Ig) G-time curve | Area under the baseline-corrected total IgG response curve from time 0 to time t | 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 | 
| Maximum decrease in total plasma IgG (Rmin) of a single dose rozanolixizumab | Rmin: Maximum decrease in total plasma IgG 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 | 
| Time to minimum IgG level (tmin) of a single dose rozanolixizumab | tmin: Time to minimum IgG level 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Study Participants, Phase 1, rozanolixizumab, manual push, syringe driver