A Phase I randomized blinded single dose comparison of the safety pharmacokinetics and pharmacodynamics of SYN008 and omalizumab (Xolair) in healthy adult subjects
Clinical Network Services (CNS) Pty Ltd
80 participants
Feb 9, 2016
Interventional
Conditions
Summary
This study is a Phase I single site randomized, and double blinded comparison of the safety pharmacokinetics, pharmacodynamics and immunogenicity of one dose of SYN008 to one dose of omalizumab (Xolair) control. The primary objective is to compare the safety of SYN008 to Omalizumab. Omalizumab is an effective therapy for both moderate to severe asthma as well as chronic idiopathic urticaria. SYN008 is intended to be a biosimilar agent (generic) to omalizumab. The availability of a highly similar alternative will help to provide a more robust marketplace and provide this treatment to more patients who might need it. The current study is performed in normal adults to reduce the background of adverse events. The dosage (single dose of 150mg) and administration (by injection under the skin) of the study drugs SYN008 and omalizumab are identical providing a comparison of the adverse reactions to the agents. The bioavailability and immunogenicity of the study drugs will be evaluated with pharmacokinetics and anti-drug antibody determinations. The effect of SYN008 and omalizumab on free IgE concentrations will be measured as a pharmacodynamic effect. A single dose will be used to reduce any long term adverse effects from the agents and to mimic the way that the antibodies will be used clinically. This initial study will enroll healthy volunteers. This latter selection is made to facilitate the safety evaluation. This study is a double blinded comparison of SYN008 and omalizumab. A total of 80 subjects will be randomized in a parallel 1:1 ratio to either SYN008 or omalizumab resulting in 40 subjects in each group. The study will be conducted at a dedicated Phase I Unit in Melbourne, Australia. The dose will be 150 mg for both study drugs. This dose is the minimum dose in the omalizumab product information. The study duration is 84 days and the screening interval is 14 days for a total duration of 98 days for an individual. The major outcomes measured in the trial will be solicited adverse events, adverse events and serious adverse events that will be collected according during the trial. The follow-up for comparison of safety (adverse events) will continue through the day 84 Study Visit. Standard assessments of serum chemistry including liver function tests, renal function tests, complete blood count, and blood clotting studies, urinalysis findings, vital signs and ECG evaluations will be performed. Baseline values for pulse oximetry and blood tryptase will be recorded to assist in adverse event evaluation. The pharmacodynamic parameter being measured is the change in free IgE serum concentrations. The development of anti-SYN008 antibodies will also be evaluated. There are 11 scheduled clinical visits after the screening visit(s).
Eligibility
Inclusion Criteria10
- To be eligible, subjects must
- Have completed the written informed consent process
- be male or female
- be aged between age 18 years and 56 years on Study Day 0
- be in general good health confirmed by medical history and physical examination
- Agree to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to move from the study area for the duration of the study
- Agree to avoid elective surgery for the full duration of the study
- For female subjects: agree to be within 14 days from the start of her last menses or have avoided pregnancy from 28 days prior to Study Day 0. Agree to avoid pregnancy until 112 days after Study Day 0. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile male sexual partner, sexual abstinence (not engaging in sexual intercourse), female hormonal contraceptives (oral, injection, transdermal patch, or implant), progesterone intrauterine device, copper intrauterine device (IUD), or condoms.
- Have body mass index (BMI) between 19 and 33 (weight/height2) by calculation: body weight (kg) divided by [height(meters)]2
- Have body weight less than or equal to 150 kg
Exclusion Criteria25
- Subjects must have none of the following :
- Acute illness on Study Day 0
- Oral temperature more than or equal to 37.5 degrees on Study Day 0
- Abnormal laboratory values per local laboratory parameters from blood collected within 14 days prior to Study Day 0 randomization as follows:
- hemoglobin, hematocrit, absolute neutrophil count, or absolute lymphocyte count below lower limit of normal (LLN)
- white blood cell count above upper limit of normal (ULN) or below LLN (i.e., must be within normal limits)
- ALT, AST, total bilirubin, alkaline phosphatase (ALP), creatinine, blood urea nitrogen (BUN), prothrombin time (PT or INR), or partial thromboplastin time (PTT) above ULN
- Urinalysis must reflect no evidence of systemic or clinically important local disease process
- Severe anemia, defined as less than 10 g/dL or hematocrit less than 30 per cent
- Evidence of significant active infection
- Previous receipt of omalizumab
- History of autoimmune disease or immunosuppression
- Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted)
- Received immunoglobulin or blood products within 42 days before Study Day 0
- Received any investigational drug therapy or investigational drug within 60 days before Study Day 0, or planned participation in any other investigational study during the study period
- Current chronic drug therapy such as insulin, or hormone replacement (thyroid replacement, estrogen and progesterone replacement and contraceptives are acceptable)
- History or laboratory evidence of any past, present, or future possible immunodeficiency state including but not limited to any laboratory indication of HIV 1 infection
- Previous medical history that may compromise the safety of the subject in the study, including but not limited to: severe impairment of pulmonary function from tuberculosis infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease; or uncontrolled epilepsy or infantile spasms
- Evidence of a new acute illness that may compromise the safety of the subject in the study
- Evidence of chronic hepatitis (e.g., hepatitis B antigen or hepatitis C antibody or PCR)
- Inability to discontinue daily medications, except contraceptives, and thyroid hormone during the study period
- History of alcohol or drug abuse within the past 2 years
- Positive urine test for illicit drugs (opiates, cocaine, amphetamines)
- History or evidence on physical examination of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the study drug, including axillary lymphadenopathy
- Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol
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Interventions
This study is a Phase I, randomized, double blind, parallel group comparison of the safety, pharmacokinetics, pharmacodynamics and immunogenicity of a single dose of SYN008 (150mg) with a single dose of omalizumab (Xolair) control (150mg) in adult healthy volunteers. Eighty subjects will be centrally randomized in a 1:1 ratio to receive either the bio-similar SYN008 or the comparator omalizumab resulting in 40 subjects per group. The study duration is 84 days consisting of an in-house stay of 3 nights (Day -1 to Day 2)followed by 6 out-patient visits (Days 3, 5, 7, 14, 28 and 56) and a follow-up visit at Day 84; the screening interval is 14 days for a total study duration of 98 days per subject. On Day 0, subjects will be administered 150mg of either SYN008 or omalizumab (Xolair) by subcutaneous injection in the thigh or abdomen.
Locations(1)
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ACTRN12616000145404