A First-In-Human Study With a Single Dose UCB7665 in Healthy Volunteers

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and tolerability of single ascending doses of UCB7665 administered by intravenous or subcutaneous infusion in healthy subjects.

Official Title
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A Subject-Blind, Investigator-blind, Randomized, Placebo-controlled, First-in-human Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous and Subcutaneous Doses of UCB7665 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Biological: UCB7665 Intravenous 1
* Biological: UCB7665 Intravenous 2
* Biological: UCB7665 Intravenous 3
* Biological: UCB7665 Intravenous 4
* Biological: UCB7665 Intravenous 5
* Biological: UCB7665 Subcutaneous 1
* Biological: UCB7665 Subcutaneous 2
* Biological: Intravenous Placebo
* Biological: Subcutaneous Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers of non-childbearing potential who gave their consent to the written informed consent form Healthy volunteers in the age between 18 and 64 years old with normal weight as determined by a body mass index (BMI) between 18 and 30 kg/m^2, with a body weight of at least 50 kg for male subjects or 45 kg for female subjects Subjects has blood pressure (BP) and pulse within normal range in a supine position after 5 minutes rest Subject has clinical laboratory test results within the reference ranges of the testing laboratory or test results that are outside the specified ranges and that are deemed as clinically non-significant Subject's electrocardiogram (ECG) is considered normal or abnormal but clinically non-significant Exclusion Criteria: Subject has had significant blood loss, or has donated blood in excess of 400 mL of blood or blood products within 90 days before Day -2, or plans to donate blood during the clinical study Subject has a total Immuneglobulin G <7 g/L or >16 g/L at the Screening Visit Subject has absolute neutrophil count <1.5x10^9/L and/or lymphocyte count <1.0x10^9/L Subject has known viral hepatitis, has a positive test for Hepatitis B surface antigen or is Hepatitis C virus antibody positive Subject tests positive to Human Immunodeficiency Virus (HIV) 1/2 antibodies Subject has a past medical history or family history of primary immunodeficiency Subject is splenectomized Subject has a positive TIGRA (T cell interferon γ release assay) at the Screening Visit. If TIGRA is not available, purified protein derivative (PPD) skin test can be substituted and/or chest x-ray performed within 6 months before the Screening Visit showing no evidence of latent/active Tuberculosis (TB) Subject has past (in the last 12 months ) or present substance abuse/dependence or concurrent medical conditions that in the opinion of the investigator could confound clinical study interpretation or affect the subject's ability to fully participate in the clinical study Subject has a known hypersensitivity to any components of the Investigational Medicinal Product (IMP) Subject has an active infection or has had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks before the first dose of IMP Subject has 12-lead electrocardiogram (ECG) with changes considered to be clinically significant upon medical review Subject has renal impairment Subject has hepatic impairment Subject has corrected serum calcium of >11.5 mg/dL (>2.9 mmol/L) or <8.0 mg/dL (<2.0 mmol/L) at the Screening Visit Subject has active neoplastic disease or history of neoplastic disease within 5 years of entry in the clinical study Subject has any other acute or chronic illness which, in the opinion of the investigator or study physician, could pose a threat or harm to the subjects Subject has received a vaccination within 6 weeks before the Screening Visit or intends to have a vaccination before Day 43 of the Safety Follow-up Period Subject has received any IMP or experimental procedure within 90 days before the first dose of IMP Subject requires a treatment other than Paracetamol during the clinical study Subject is a vulnerable subject (e.g. subject kept in detention) (Declaration of Helsinki, 1996)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UCB7665 Intravenous 1<br>Single dose calculated based on body weight for 60 minutes intravenous infusion. | Biological: UCB7665 Intravenous 1<br>* Active substance: UCB7665 Pharmaceutical form: solution Concentration: 140 mg/mL Route of Administration: intravenous infusion<br>|
| Experimental: UCB7665 Intravenous 2<br>Single dose calculated based on body weight for 60 minutes intravenous infusion. | Biological: UCB7665 Intravenous 2<br>* Active substance: UCB7665 Pharmaceutical form: solution Concentration: 140 mg/mL Route of Administration: intravenous infusion<br>|
| Experimental: UCB7665 Intravenous 3<br>Single dose calculated based on body weight for 60 minutes intravenous infusion. | Biological: UCB7665 Intravenous 3<br>* Active substance: UCB7665 Pharmaceutical form: solution Concentration: 140 mg/mL Route of Administration: intravenous infusion<br>|
| Experimental: UCB7665 Intravenous 4<br>Single dose calculated based on body weight for 60 minutes intravenous infusion. | Biological: UCB7665 Intravenous 4<br>* Active substance: UCB7665 Pharmaceutical form: solution Concentration: 140 mg/mL Route of Administration: intravenous infusion<br>|
| Experimental: UCB7665 Intravenous 5<br>Single dose calculated based on body weight for 60 minutes intravenous infusion. | Biological: UCB7665 Intravenous 5<br>* Active substance: UCB7665 Pharmaceutical form: solution Concentration: 140 mg/mL Route of Administration: intravenous infusion<br>|
| Experimental: UCB7665 Subcutaneous 1<br>Single dose calculated based on body weight for 60 minutes subcutaneous infusion. | Biological: UCB7665 Subcutaneous 1<br>* Active substance: UCB7665 Pharmaceutical form: solution Concentration: 140 mg/mL Route of Administration: subcutaneous infusion<br>|
| Experimental: UCB7665 Subcutaneous 2<br>Single dose calculated based on body weight for 60 minutes subcutaneous infusion. | Biological: UCB7665 Subcutaneous 2<br>* Active substance: UCB7665 Pharmaceutical form: solution Concentration: 140 mg/mL Route of Administration: subcutaneous infusion<br>|
| Placebo Comparator: Intravenous Placebo<br>Single dose placebo comparator for each active arm of intravenous infusion. | Biological: Intravenous Placebo<br>* Active substance: Placebo Pharmaceutical form: solution Concentration: 0.9 % saline Route of Administration: intravenous infusion<br>|
| Placebo Comparator: Subcutaneous Placebo<br>Single dose placebo comparator for each active arm of subcutaneous infusion. | Biological: Subcutaneous Placebo<br>* Active substance: Placebo Pharmaceutical form: solution Concentration: 0.9 % saline Route of Administration: subcutaneous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events during the study |  | Day -1 up to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | The value of the maximum plasma concentration will be directly obtained from the observed plasma concentration versus time curves. Pharmacokinetic samples will be taken predose, 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, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 
| Area under the curve from 0 to infinity (AUC) | AUC will be calculated using plasma concentrations taken at predose, 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, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 
| Area under the curve from time 0 to time t, the time of last quantifiable concentration [AUC(0-t)] | AUC(0-t) will be calculated using plasma concentrations taken at predose, 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, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 
| Time to reach Cmax (Tmax) | Tmax will be directly obtained from the observed plasma concentration versus time curves, using plasma concentrations taken at predose, 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, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 
| Total Immunoglobulin G (IgG ) concentrations | Total Immunoglobulin G will be measured at predose, 24, 48, 72, and 96 hours postdose; and on Days 7, 10, 13, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 
| Immunoglobulin G1 subclass concentrations | Immunoglobulin subclass will be measured at predose, 24, 48, 72, and 96 hours postdose; and on Days 7, 10, 13, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 
| Immunoglobulin G2 subclass concentrations | Immunoglobulin subclass will be measured at predose, 24, 48, 72, and 96 hours postdose; and on Days 7, 10, 13, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 
| Immunoglobulin G3 subclass concentrations | Immunoglobulin subclass will be measured at predose, 24, 48, 72, and 96 hours postdose; and on Days 7, 10, 13, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 
| Immunoglobulin G4 subclass concentrations | Immunoglobulin subclass will be measured at predose, 24, 48, 72, and 96 hours postdose; and on Days 7, 10, 13, 16, 19, 22, 29, 43, 57, and 85. | Predose (Day 1) up to Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monoclonal antibody, subjects, First in human