A Phase I randomized blinded single dose comparison of the safety pharmacokinetics and pharmacodynamics of SYN008 and omalizumab (Xolair) in healthy adult subjects
- Conditions
- Moderate to severe persistent asthmaChronic idiopathic urticariaInflammatory and Immune System - AllergiesRespiratory - Asthma
- Registration Number
- ACTRN12616000145404
- Lead Sponsor
- Clinical Network Services (CNS) Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 80
To be eligible, subjects must
1.Have completed the written informed consent process
2.be male or female
3.be aged between age 18 years and 56 years on Study Day 0
4.be in general good health confirmed by medical history and physical examination
5.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
6.Agree to avoid elective surgery for the full duration of the study
7.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.
8.Have body mass index (BMI) between 19 and 33 (weight/height2) by calculation: body weight (kg) divided by [height(meters)]2
9.Have body weight less than or equal to 150 kg
Subjects must have none of the following :
1.Acute illness on Study Day 0
2.Oral temperature more than or equal to 37.5 degrees on Study Day 0
3.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
4.Urinalysis must reflect no evidence of systemic or clinically important local disease process
5.Severe anemia, defined as less than 10 g/dL or hematocrit less than 30 per cent
6.Evidence of significant active infection
7.Previous receipt of omalizumab
8.History of autoimmune disease or immunosuppression
9.Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted)
10.Received immunoglobulin or blood products within 42 days before Study Day 0
11.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
12.Current chronic drug therapy such as insulin, or hormone replacement (thyroid replacement, estrogen and progesterone replacement and contraceptives are acceptable)
13.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
14.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
15.Evidence of a new acute illness that may compromise the safety of the subject in the study
16.Evidence of chronic hepatitis (e.g., hepatitis B antigen or hepatitis C antibody or PCR)
17.Inability to discontinue daily medications, except contraceptives, and thyroid hormone during the study period
18.History of alcohol or drug abuse within the past 2 years
19.Positive urine test for illicit drugs (opiates, cocaine, amphetamines)
20.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
21.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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety: comparison of the adverse event profile of SYN008 with omalizumab (Xolair Registered Trademark)<br>Expected adverse events are as for listed in the Xolair product information and include: nausea, nasopharyngitis, sinusitis, upper respiratory infection, arthralgia, headache and cough.<br>These will be assessed by close medical monitoring and questioning of subjects at the Phase I unit for 48 hours post-dose and at outpatient visits on days 3, 5, 7, 14, 28 ,56, and 84[Screening, Day -1, Day 0 (pre- and post-IP administration), and at Days 1, 2, 3, 5, 7, 14, 28 ,56 ,and 84 following the single dose administration of IP on Day 0.]
- Secondary Outcome Measures
Name Time Method Pharmacokinetic: Comparison of the pharmacokinetic profile of SYN008 to omalizumab (Xolair Registered Trademark) in serum.<br>The following parameters will be determined for each individual: Cmax, Tmax, t1/2, AUC0-t, lambda, Volume of distribution for each study drug administration. [Day 0 (pre-IP administration and 12 hrs post IP administration), and at Days 1, 3, 5, 7, 14, 28, 56 and 84 following the single dose administration of IP on Day 0.];Pharmacodynamic: Comparison of the free IgE lowering effects of SYN008 to omalizumab (Xolair Registered Trademark) in serum samples.<br>[At screening, Day 0 (pre-dose), and at Days 1,3, 5, 7, 14, 28, and 56 following the single dose administration of IP on Day 0.];Comparison of the immunogenicity of SYN008 to omalizumab (Xolair Registered Trademark) in serum samples.<br>[Day 0,pre-dose and at Days 7, 14, 28, 56 and 84 following the single dose administration of IP on Day 0.]