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

• ClinicalTrials.gov Identifier: NCT04828343
• Recruitment Status: Completed
• First Posted: April 2, 2021
• Results First Posted: March 7, 2024
• Last Update Posted: March 7, 2024
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Tracking Information

• First Submitted Date: March 30, 2021
• First Posted Date: April 2, 2021
• Results First Submitted Date: July 27, 2023
• Results First Posted Date: March 7, 2024
• Last Update Posted Date: March 7, 2024
• Actual Study Start Date: April 22, 2021
• Actual Primary Completion Date: April 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 27, 2023)

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From start of dosing (Day 1) to End of Safety Follow-Up (up to Day 57) ]

A TEAE was defined as any adverse event (AE) with a start date/time on or after first dose of study medication until 8 weeks after dosing of study medication.

Original Primary Outcome Measures (submitted: March 30, 2021)

Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: July 27, 2023)

• Maximum Plasma Concentration (Cmax) of a Single Dose Rozanolixizumab [ Time Frame: Sampling time points for plasma Pharmacokinetics were 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 was the maximum plasma concentration of a single dose rozanolixizumab. Cmax was measured in micrograms per millilitre per milligram (ug/mL/mg).
• Time to Maximum Plasma Concentration (Tmax) of a Single Dose Rozanolixizumab [ Time Frame: Sampling time points for plasma Pharmacokinetics were 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 was the 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 [ Time Frame: Sampling time points for plasma Pharmacokinetics were 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 was the 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 [ Time Frame: Sampling time points for total IgG were 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.
• Percent Maximum Decrease in Total Plasma IgG (Rmin) of a Single Dose Rozanolixizumab or Placebo [ Time Frame: Sampling time points for total IgG were 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 was the maximum (max) decrease in total plasma IgG of a single dose rozanolixizumab or placebo.
• Time to Minimum IgG Level (Tmin) of a Single Dose Rozanolixizumab or Placebo [ Time Frame: Sampling time points for total IgG were 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 was the time to minimum IgG level of a single dose rozanolixizumab or placebo.

Original Secondary Outcome Measures (submitted: March 30, 2021)

• Maximum plasma concentration (Cmax) of a single dose rozanolixizumab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Rozanolixizumab Administered Subcutaneously Via Manual Push Versus Syringe Driver to Healthy Participants
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

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

• Condition: Healthy Study Participants

Intervention

• Drug: rozanolixizumab
  Study participants will receive a single dose rozanolixizumab subcutaneously administered by manual push or a syringe driver.
  Other Name: RLZ
• Other: Placebo
  Study participants will receive a single dose placebo subcutaneously administered by manual push or a syringe driver.
  Other Name: PBO

Study Arms

• 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.
  Interventions:

  • Drug: rozanolixizumab
  • Other: Placebo
• 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.
  Interventions:

  • Drug: rozanolixizumab
  • Other: Placebo
• 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.
  Interventions:

  • Drug: rozanolixizumab
  • Other: Placebo
• 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.
  Interventions:

  • Drug: rozanolixizumab
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 30, 2021): 32
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 11, 2022
• Actual Primary Completion Date: April 11, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT04828343
• Other Study ID Numbers: UP0106
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Due to the small sample size in this trial, IPD cannot be adequately anonymized i.e., there is a reasonable likelihood that individual participants could be re-identified. For this reason, data from this trial cannot be shared.

• Current Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• Original Responsible Party: Same as current
• Current Study Sponsor: UCB Biopharma SRL
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; 001 844 599 2273

• PRS Account: UCB Pharma
• Verification Date: July 2023