Clinical trial NCT02220153: A First-In-Human Study With a Single Dose UCB7665 in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Monoclonal antibody
subjects
First in human
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2014-08-19
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of adverse events during the study
timeFrame: Day -1 up to Day 85
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: Predose (Day 1) up to Day 85
measure: Area under the curve from 0 to infinity (AUC)
timeFrame: Predose (Day 1) up to Day 85
measure: Area under the curve from time 0 to time t, the time of last quantifiable concentration [AUC(0-t)]
timeFrame: Predose (Day 1) up to Day 85
measure: Time to reach Cmax (Tmax)
timeFrame: Predose (Day 1) up to Day 85
measure: Total Immunoglobulin G (IgG ) concentrations
timeFrame: Predose (Day 1) up to Day 85
measure: Immunoglobulin G1 subclass concentrations
timeFrame: Predose (Day 1) up to Day 85
measure: Immunoglobulin G2 subclass concentrations
timeFrame: Predose (Day 1) up to Day 85
measure: Immunoglobulin G3 subclass concentrations
timeFrame: Predose (Day 1) up to Day 85
measure: Immunoglobulin G4 subclass concentrations
timeFrame: Predose (Day 1) up to Day 85
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: 001
state: Middlesex
Study officials:
affiliation: UCB Pharma
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Kiessling P, Lledo-Garcia R, Watanabe S, Langdon G, Tran D, Bari M, Christodoulou L, Jones E, Price G, Smith B, Brennan F, White I, Jolles S. The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017 Nov 1;9(414):eaan1208. doi: 10.1126/scitranslmed.aan1208.