A Study to Evaluate Safety and Tolerability of Single Ascending Doses of Rozanolixizumab Administered by Subcutaneous Infusion in Healthy Japanese, Chinese and Caucasian Study Participants

Study Overview
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Brief Summary
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The purpose of the study is to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of rozanolixizumab in japanese, chinese and caucasian healthy-volunteer study participants.

Official Title
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A Randomized, Participant-Blind, Investigator-Blind, Placebo-Controlled Study Comparing Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Subcutaneous Doses of Rozanolixizumab in Japanese, Chinese and Caucasian Healthy-Volunteer Study Participants

Conditions
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Healthy-volunteers

Intervention / Treatment
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* Drug: Rozanolixizumab
* Drug: 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, at the time of signing the Informed Consent form (ICF) Study participants who are overtly healthy in the opinion of the investigator as determined by medical history and a general clinical examination, including physical examination, laboratory tests, and cardiac monitoring Study participant must be considered reliable and capable of adhering to the protocol, according to the judgment of the investigator, and is able to communicate satisfactorily with the investigator and comply with all clinical study requirements Japanese or Chinese study participant is of Japanese or Chinese descent, determined by verbal confirmation of familial heritage with all 4 grandparents of Japanese or Chinese descent Caucasian study participant is of Caucasian descent as evidenced in appearance and verbal confirmation of familial heritage with all 4 grandparents of Caucasian descent Study participant is of normal weight as determined by a body mass index (BMI) between 18 and 32 kg/m2, inclusive, with a body weight of at least 50 kg (male) or 45 kg (female) and no greater than 100 kg Exclusion Criteria: Any medical (acute or chronic illness) or psychiatric condition that, in the opinion of the investigator, could harm the study participant or would compromise the study participant's ability to participate in this study. History of known inflammatory bowel disease, active diverticular disease, or a history of confirmed duodenal, gastric, or esophageal ulceration in the previous 6 months Significant allergies to humanized monoclonal antibodies Known hypersensitivity to any components of the investigational medicinal product (IMP) Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis) Current or chronic history of liver disease, or known hepatic or biliary abnormalities Study participant is splenectomized, or has a clinically relevant active infection (eg, sepsis, pneumonia, abscess) or has had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to study treatment Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing Received a vaccination within 8 weeks prior to Day -1; or intends to have a vaccination during the course of the study. Prior/Concurrent clinical study experience Exposure to more than 3 new chemical entities within 12 months prior to dosing Previously participated in this clinical study or has previously been assigned to treatment in a clinical study of IMP under investigation in this clinical study Participated in another study of an 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)

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1 of rozanolixizumab in Japanese subjects<br>Japanese subjects will be randomized to receive a predefined dosage of rozanolixizumab in order to maintain the blinding. | Drug: Rozanolixizumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Experimental: Dose 2 of rozanolixizumab in Japanese subjects<br>Japanese subjects will be randomized to receive a predefined dosage of rozanolixizumab in order to maintain the blinding. | Drug: Rozanolixizumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Experimental: Dose 3 of rozanolixizumab in Japanese subjects<br>Japanese subjects will be randomized to receive a predefined dosage of rozanolixizumab in order to maintain the blinding. | Drug: Rozanolixizumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Experimental: Dose 1 of rozanolixizumab in Caucasian subjects<br>Caucasian subjects will be randomized to receive a predefined dosage of rozanolixizumab in order to maintain the blinding. | Drug: Rozanolixizumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Experimental: Dose 2 of rozanolixizumab in Caucasian subjects<br>Caucasian subjects will be randomized to receive a predefined dosage of rozanolixizumab in order to maintain the blinding. | Drug: Rozanolixizumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Experimental: Dose 3 of rozanolixizumab in Caucasian subjects<br>Caucasian subjects will be randomized to receive a predefined dosage of rozanolixizumab in order to maintain the blinding. | Drug: Rozanolixizumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Experimental: Dose 2 of rozanolixizumab in Chinese subjects<br>Chinese subjects will be randomized to receive a predefined dosage of rozanolixizumab in order to maintain the blinding. | Drug: Rozanolixizumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Experimental: Dose 3 of rozanolixizumab in Chinese subjects<br>Chinese subjects will be randomized to receive a predefined dosage of rozanolixizumab in order to maintain the blinding. | Drug: Rozanolixizumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Placebo Comparator: Placebo in Japanese subjects<br>Japanese subjects will be randomized to receive a predefined dosage of placebo in order to maintain the blinding. | Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Placebo Comparator: Placebo in Chinese subjects<br>Chinese subjects will be randomized to receive a predefined dosage of placebo in order to maintain the blinding. | Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|
| Placebo Comparator: Placebo in Caucasian subjects<br>Caucasian subjects will be randomized to receive a predefined dosage of placebo in order to maintain the blinding. | Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events (TEAEs) from Baseline to Safety Follow-up (SFU) in healthy Japanese study participants | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline until Safety Follow-up (up to Week 8) | 
| Treatment-emergent adverse events (TEAEs) from Baseline to Safety Follow-up (SFU) in healthy Chinese study participants | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline until Safety Follow-up (up to Week 8) | 
| Maximum observed plasma concentration (Cmax) of rozanolixizumab in healthy Japanese study participants | Maximum observed plasma concentration (Cmax) | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| Maximum observed plasma concentration (Cmax) of rozanolixizumab in healthy Chinese study participants | Maximum observed plasma concentration (Cmax) | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| Time to maximum observed plasma concentration (tmax) of rozanolixizumab in healthy Japanese study participants | Time of observed Cmax (tmax) | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| Time to maximum observed plasma concentration (tmax) of rozanolixizumab in healthy Chinese study participants | Time of observed Cmax (tmax) | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| Area under the concentration-time curve from time 0 to time t (AUC(0-t)) of rozanolixizumab in healthy Japanese study participants | AUC(0-t): Area under the curve from time 0 to time t, the time of last quantifiable concentration | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| Area under the concentration-time curve from time 0 to time t (AUC(0-t)) of rozanolixizumab in healthy Chinese study participants | AUC(0-t): Area under the curve from time 0 to time t, the time of last quantifiable concentration | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events (TEAEs) from Baseline to Safety Follow-up (SFU) in healthy Caucasian | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline until Safety Follow-up (up to Week 8) | 
| AUC(0-t)/BW: Body weight normalized AUC(0-t) of rozanolixizumab | AUC(0-t)/BW: Body weight normalized AUC(0-t) of rozanolixizumab in healthy Japanese, Chinese and Caucasian study participants | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| AUC(0-t)/D: Dose normalized AUC(0-t) | AUC(0-t)/D: Dose normalized AUC(0-t) of rozanolixizumab in healthy Japanese, Chinese and Caucasian study participants | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| AUC(0-t)/D/BW: Dose and body weight normalized AUC(0-t) | AUC(0-t)/D/BW: Dose and body weight normalized AUC(0-t) of rozanolixizumab in healthy Japanese, Chinese and Caucasian study participants | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| Cmax/BW: Body weight normalized Cmax of rozanolixizumab | Cmax/BW: Body weight normalized Cmax of rozanolixizumab in healthy Japanese, Chinese and Caucasian study participants | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| Cmax/D: Dose normalized Cmax | Cmax/D: Dose normalized Cmax of rozanolixizumab in healthy Japanese, Chinese and Caucasian study participants | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 
| Cmax/D/BW: Dose and body weight normalized Cmax | Cmax/D/BW: Dose and body weight normalized Cmax of rozanolixizumab in healthy Japanese, Chinese and Caucasian study participants | Sampling time points for plasma Pharmacokinetics will be as follows: predose, immediately after the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144 and 216 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rozanolixizumab, Caucasian healthy-volunteers, Japanese healthy-volunteers, Phase 1, UCB7665, Chinese healthy-volunteers