None listed
Conditions
Brief summary
Conditions such as asthma, Atopic Dermatitis (AD) and food allergies are all characterised by abnormal immune responses to an external stimuli that ultimately leads to a potentially life threatening inflammatory state. One protein which is key to triggering this inflammatory cascade is the protein IL-33. Animal studies have shown that by inhibiting IL-33, the detrimental inflammatory cascade is suppressed. AnaptysBio Pty Ltd is developing the drug ANB020 to treat these and other related conditions also associated with abnormal inflammatory responses. ANB020 is a monoclonal antibody (mAb) meaning that it can specifically bind to and inhibit IL-33. This study will be conducted in two parts: the first part will investigate the effect of a single dose of ABN020 and the second part will investigate the effect of multiple (weekly) doses of ABN020 for 4 weeks. The single dose study will explore different doses of the study drug given either via a subcutaneous (under the skin) injection (SC) or via an intravenous (into the vein) infusion (IV). The results from this part will be used to determine the dose and route of administration to be used for the multiple dose part of the study. Over the entire study a total of 96 people will be enrolled over 12 dosing groups/ cohorts. In each group of 8 participants, 6 will receive the active drug, ANB020 and the other 2 will receive an equivalent placebo (an injection/ infusion that looks identical to the active drug, but contains no active drug). This study is a dose escalation study meaning that the first group/ cohort will receive the lowest dose of study drug. Results will be reviewed by a safety monitoring committee after each dose strength has been tested to make sure that it is safe to continue with the next higher dose strength in the next group. The next group will not be enrolled until the safety monitoring committee have confirmed it is safe to do so. The study can be stopped at any time, based on evaluation of the side effects of the study drug. As this is a first in human study, the primary objective of the study is to assess the safety and tolerability of single and multiple doses of ANB020 administered to healthy humans.
Interventions
This is a first-in human study of ANB020. It is a double-blind, randomized, placebo controlled, ascending single (SAD) and multiple-doses (MAD) study in healthy male and female subjects.
The study is planned to have approximately nine cohorts in the SAD section and approximately three in the MAD section of the study. Cohorts maybe added or removed upon interim analyses evaluations.
Eight (8) healthy subjects will be assigned to all single and multiple dose cohorts at predicted doses ranging from
This is a first-in human study of ANB020. It is a double-blind, randomized, placebo controlled, ascending single (SAD) and multiple-doses (MAD) study in healthy male and female subjects. The study is planned to have approximately nine cohorts in the SAD section and approximately three in the MAD section of the study. Cohorts maybe added or removed upon interim analyses evaluations. Eight (8) healthy subjects will be assigned to all single and multiple dose cohorts at predicted doses ranging from 10mg to 750mg. The study drug will be administered by subcutaneous (SC) injection (doses of 10 mg, 40 mg, 100 mg, 150 mg, or 300 mg) or intravenous (IV) infusion (doses of 40 mg, 100 mg, 300 mg or 750 mg) for the SAD part. For the MAD part, the doses and administration method (SC or IV) will be determined based on the results from the SAD part. The infusion time for the IV infusion cohorts will be 1 hour. Each SC or IV dose cohort of eight participants, for both the SAD and MAD parts, will be distributed on a 3:1 ratio to receive ANB020 (six participants) or placebo (two participants). Subjects in the single dose cohorts will be admitted to the clinical facility on Day -1 and will remain in the clinic for up to 3 days for a total of up to 4 days in-house. Dosing of ANB020 or placebo will occur on Day 1. Safety PK and PD assessments will be performed during the study.Subjects will return to the facility on Days 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 for additional PK, immunogenicity, PD and end of study safety assessments. Subjects in the multiple-dose cohort(s) will be admitted to the clinical facility on the morning of Day-1 and will remain in the clinic for 3 days for a total of 4 days in-house. Following this in-house period, subjects will be admitted the evening prior to their next dosing day and discharged the evening of the day of dosing for a total of 3 additional doses of ANB020 and 3 additional days in-for a total of 7 days in-house. Each subject will receive 4 doses of ANB020 or placebo, administered weekly by SC injection. Following the last dose of study drug on Day 22 of the study, subjects will return to the facility on Days 29, 36, 43, 57 and 85 for additional PK, immunogenicity, PD and end of study safety assessments. In order to monitor participants adherence to the treatment schedule, all the study drug administrations will be performed on-site by the study staff.
Sponsors
AnaptysBio Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy male and female as determined by a lack of clinically significant medical history, physical examination, ECGs, and clinical laboratory determinations.
Exclusion criteria
Medical History and Concurrent Diseases: a) Any significant acute or chronic medical illness. b) History of bacterial or viral infections that led to hospitalization and IV antibiotic or antiviral treatment within 3 months prior to screening, or any recent infection requiring antibiotic or antiviral treatment within 4 weeks of Day 1. c) History of recurrent or chronic sinusitis, bronchitis, pneumonia, urinary tract infection (recurrent or chronic infection is 2 episodes within 6 months). d) History of malaria (excluding falciparum). e) History or any evidence of active infection or febrile illness within 7 days of dosing (e.g., bronchopulmonary, urinary, or gastrointestinal). f) Active, or history of, parasitic infections such as, but not exclusively, helminth, protozoa, Trypanosoma cruzi. g) Subjects with a positive quantiFERON (Registered Trademark) test at screening or within 6 months prior to Day 1 will not be eligible for the study. h) Known or suspected autoimmune disorder, including but not limited to rheumatoid arthritis, fibromyalgia, systemic lupus erythematosus, polymyalgia rheumatica, giant cell arteritis, Behcet’s disease, dermatomyositis, multiple sclerosis, moderate to severe asthma, or other severe forms of atopy, any autoimmune vasculitis, autoimmune hepatitis, or any other active autoimmune disease for which a subject requires medical follow-up or medical treatment. i) Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the subject’s immune status (e.g., history of splenectomy). j) Presence of any factors that would predispose the subject to develop infection e.g., rectal fissures, poor dentition, open skin lesions, and presence of preexisting skin conditions that increase risks for injection site complications e.g. Behcet’s Disease, Psoriasis, pustular dermatoses. k) Current or recent (within 3 months of study drug administration) gastrointestinal disease. l) Any major surgery within 4 weeks of study drug administration. m) Any gastrointestinal surgery that could impact upon the absorption of study drug. n) Donation of blood to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration (within 2 weeks for plasma only). o) Blood transfusion within 4 weeks of study drug administration. p) Inability to tolerate IV or SC drug administration q) Inability to be venipunctured and/or tolerate venous access. r) Previous administration of mAbs s) Smoking more than 10 cigarettes per day. t) Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in DSM V, Diagnostic Criteria for Drug and Alcohol Abuse. u) Any other sound medical, psychiatric and/or social reason as determined by the Investigator. Physical and Laboratory Test Findings: a) Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population. b) Alanine aminotransferase (ALT) levels greater than ULN, confirmed by one repeat. c) Total and unconjugated bilirubin greater than ULN, confirmed by one repeat. Subjects with a previously documented diagnosis of Gilbert’s disease who have serum bilirubin less or equal to 3 x ULN may be enrolled. d) Evidence of clinically significant abnormality in urinalysis testing as determined by the Investigator. e) Abnormal chest x-ray. f) Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration, confirmed by repeat. i) PR greater than or equal to 210 msec ii) QRS greater than or equal to 120 msec iii) QT greater than or equal to 500 msec iv) QTcF greater than or equal to 450 msec g) Positive urine screen for drugs of abuse. h) Positive breathalyzer test for recent alcohol consumption. i) Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibodies or p24 antigen (HIV viral RNA test may be conducted if the Investigator deems necessary).
Outcome results
None listed