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Trial registered on ANZCTR


Registration number
ACTRN12616000049471
Ethics application status
Approved
Date submitted
15/01/2016
Date registered
19/01/2016
Date last updated
26/04/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I Study to evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic profile of single and multiple dose of ANB020 in Healthy Subjects.
Scientific title
A Double-Blinded, Randomized, Placebo-Controlled, Single Ascending
Dose (SAD) and Multiple Ascending Dose (MAD) Study to Evaluate the
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ANB020
in Healthy Subjects.
Secondary ID [1] 288333 0
Sponsor Study Number: ANB020-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Food Allergies 297322 0
Asthma 297324 0
Atopic Dermatitis 297325 0
Condition category
Condition code
Inflammatory and Immune System 297500 297500 0 0
Allergies
Respiratory 297501 297501 0 0
Asthma
Skin 297502 297502 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 293627 0
Treatment: Drugs
Comparator / control treatment
Placebo for ANB020 is formulated as 50 mM sodium acetate, 103 mM sodium chloride, 0.02% polysorbate-80, pH 5.7. This is the same formulation as the active product except that it contains no active ingredient. As with the active product, the Placebo for ANB020 is filled to a total volume of 1.2 mL in a 2-mL type I glass vial.
Control group
Placebo

Outcomes
Primary outcome [1] 297062 0
Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests. The incidence of observed adverse events will be tabulated and reviewed for potential significance and clinical importance.
Timepoint [1] 297062 0
For SAD part: safety blood sampling will be collected at screening (any time in the 21 days interval before the randomization), at check-in on the day before randomization, on day 1 after the dose administration and on each of the days 3, 8, 15, 22, 29, 36, 43, 57 and 85; vital signs will be measured at screening, at check-in, after dose administration and on each of the days 2, 3, 8, 15, 22, 29, 36, 43, 57 and 85 ;ECG will be performed during screening, on day -1, day 2 and day 85; the Adverse Events will be assessed continuously from the time of the first administration of IMP through discharge from the study at the follow-up visit.

For the MAD part: safety blood sampling will be collected at screening (any time in the 21 days interval before the randomization), at check-in on the day before randomization, on day 1 after the dose administration and on each of the days 8, 15, 22, 29, 36, 43, 57 and 85; vital signs will be measured at screening, at check-in, after dose administration and on each of the days 8, 15, 22, 29, 36, 43, 57 and 85 ;ECG will be performed during screening, on day -1, days 8, 15, 22 and 85; the Adverse Events will be assessed continuously from the time of the first administration of IMP through discharge from the study at the follow-up visit.
Secondary outcome [1] 319944 0
Pharmacokinetic parameters (Cmax, Tmax, AUC (0-T), AUC(INF), T-HALF, CLT (IV
only), CLT/F (SC only), Vz (IV only), Vss (IV only), Vz/F (SC only), and F (SC only)) will be derived from plasma concentration of ANB020 or its metabolite versus time data.
Timepoint [1] 319944 0
For the SAD part: for SC administered drug the PK collection timepoints are: Pre-Dose, Post-dose at 30 minutes, 1 hour, 4, 8, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1368 and 2040 hours; for the IV administered drug the PK collection timepoints are: Pre-Dose, Post-dose at 30 minutes, 1 hour, 2, 4, 24, 48, 168, 336, 504, 672, 840, 1008, 1368 and 2040 hours.

For the MAD cohorts, the PK collection timepoints are: for Day 1, 8 and 15, Pre-Dose, 1 hour and 4 hours post dose, on Day 22 Pre-Dose, 1 hour, 4, 8 , 168, 336, 504, 672 and 840 hours post last dose.
Secondary outcome [2] 319945 0
Presence of anti-drug antibodies measured with an immunoassay method to measure antibodies against ANB020 in human serum.
Timepoint [2] 319945 0
For the SAD part, both SC and IV administration methods, the anti-drug antibodies are collected at the following timepoints: Pre-Dose, 672 and 2040 hours Post-Dose.
For the MAD part, the anti-drug antibodies are collected at the following timepoints: Pre-Dose before the dosing on each of the days 1, 8, 15 and 22 and at 840 hours since the last dose administration.
Secondary outcome [3] 319946 0
ANB020 "ex vivo" inhibition of cytokine release (INF-gamma) upon IL-33 stimulation performed using whole blood collected from the participant.
Timepoint [3] 319946 0
For the SAD part, both SC and IV administration methods, whole blood will be collected for the INF-gamma assay at the following time-points: Pre-Dose, 24, 168, 504 and 1008 hours Post-Dose.

For the MAD part, whole blood will be collected for the INF-gamma assay at the following time-points: Pre-Dose, 168 and 504 hours.

Eligibility
Key inclusion criteria
Healthy male and female as determined by a lack of clinically significant medical history, physical examination, ECGs, and clinical laboratory determinations.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomization.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
This is an ascending dose study divided into two parts. The SAD part, in which, depending on the safety of the drug observed on a cohort, the dose might be increased. If the safety and pharmacokinetic and pharmacodynamic parameters attain levels acceptable to the sponsor and Safety Review Team (SRT), the study will proceed to the multiple ascending dose (MAD) phase. As well, during the MAD part, the decision to escalated the dose will be taken by the SRT based on the safety parameters observed until that moment.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
No formal sample size calculation has been made. Subject numbers are based on empirical assessments and prior experience of this study type, and are considered sufficient to meet the objectives of the study. There is no formal primary research hypothesis to be statistically tested.
Safety Analysis - Demographics and baseline characteristics (gender, race, age, body weight, height, Body Mass Index (BMI) and et al.) will be tabulated by treatments (route of administration and dose levels) using descriptive statistics. Separate Analyses will be done for single and multiple dose cohorts.
PK parameters will be summarized by treatment (dose and route of administration). Geometric means and coefficients of variation will be presented for Cmax and AUCs. Medians and ranges will be presented for Tmax. Additionally, scatter plots of Cmax, AUC(0-T), and AUC(INF) versus dose will be provided for each route of administration to assess the dependency on dose. A statistical analysis using a power model will be applied to assess dose proportionality in SC dose cohorts. Means and standard deviations will be provided for the other pharmacokinetic parameters. Separate analyses will be performed for SC and IV dose cohorts and also for single and multiple dose cohorts.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2016
Actual
22/02/2016
Date of last participant enrolment
Anticipated
1/08/2016
Actual
13/09/2016
Date of last data collection
Anticipated
Actual
5/12/2016
Sample size
Target
96
Accrual to date
Final
96
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5052 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 12539 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 292696 0
Commercial sector/Industry
Name [1] 292696 0
AnaptysBio Pty Ltd
Country [1] 292696 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
AnaptysBio Pty Ltd
Address
Level 19, HWT Tower,
40 City Road,
Southbank,
Victoria, 3006
Country
Australia
Secondary sponsor category [1] 291422 0
Commercial sector/Industry
Name [1] 291422 0
CPR Pharma Services Pty Ltd
Address [1] 291422 0
28 Dalgleish Street,
Thebarton, Adelaide,
South Australia, 5031
Country [1] 291422 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294177 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 294177 0
192 Glen Osmond Road,
Eastwood, Adelaide,
South Australia 5063
Ethics committee country [1] 294177 0
Australia
Date submitted for ethics approval [1] 294177 0
03/12/2015
Approval date [1] 294177 0
14/01/2016
Ethics approval number [1] 294177 0
2015-12-799

Summary
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.
Trial website
Trial related presentations / publications
None.
Public notes

Contacts
Principal investigator
Name 62766 0
Dr Jason Lickliter
Address 62766 0
Nucleus Network, The Burnet Tower, 5-th Floor,
89 Commercial Road,
Melbourne,
Victoria, 3004
Country 62766 0
Australia
Phone 62766 0
+61 3 90768960
Fax 62766 0
+61 3 90768911
Email 62766 0
[email protected]
Contact person for public queries
Name 62767 0
Dr Jason Lickliter
Address 62767 0
Nucleus Network, The Burnet Tower, 5-th Floor,
89 Commercial Road,
Melbourne,
Victoria, 3004
Country 62767 0
Australia
Phone 62767 0
+61 3 90768960
Fax 62767 0
+61 3 90768911
Email 62767 0
[email protected]
Contact person for scientific queries
Name 62768 0
Dr Jason Lickliter
Address 62768 0
Nucleus Network, The Burnet Tower, 5-th Floor,
89 Commercial Road,
Melbourne,
Victoria, 3004
Country 62768 0
Australia
Phone 62768 0
+61 3 90768960
Fax 62768 0
+61 3 90768911
Email 62768 0
[email protected]

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