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Trial registered on ANZCTR


Trial ID
ACTRN12617000369325
Ethics application status
Approved
Date submitted
6/03/2017
Date registered
10/03/2017
Date last updated
12/01/2018
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 ANB019 in Healthy Subjects and Psoriasis Patients.
Scientific title
A Double-Blind, Randomized, Placebo-Controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ANB019 in Healthy Subjects and Psoriasis Patients.
Secondary ID [1] 291367 0
Sponsor Study Number: ANB019-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Generalized Pustular Psoriasis 302351 0
Palmoplantar Pustolosis 302352 0
Plaque Psoriasis 302353 0
Condition category
Condition code
Inflammatory and Immune System 301939 301939 0 0
Autoimmune diseases
Skin 301988 301988 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a first-in human study of ANB019. It is a double-blind, randomized, placebo controlled, ascending single (SAD) and multiple-doses (MAD) study in healthy participants with one single dose plaque psoriasis patient cohort.
The study is planned to have approximately seven cohorts in the SAD section (six for the healthy participants and one for the plaque psoriasis patients) and approximately three in the MAD section of the study (healthy participants only).
Eight (8) healthy participants will be assigned to all single and multiple dose healthy participants cohorts at predicted doses ranging from 10mg to 750mg. 15 plaque psoriasis patients will be assigned to a single dose cohort. The study drug will be administered by subcutaneous (SC) or intravenous (IV) infusion. For the MAD part and the plaque psoriasis patient cohort, the doses and administration method (SC or IV) will be determined based on the results from the healthy participant SAD part.. Participants 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 ANB019 or placebo will occur on Day 1. Safety PK and PD assessments will be performed during the study.
Participants in the multiple-dose cohort(s) will be admitted to the clinical facility on Day-1 and will remain in the clinic for 3 days for a total of 4 days in-house. Following this in-house period, participants 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 ANB019 and 3 additional days in-house for a total of 7 days.
Intervention code [1] 297396 0
Treatment: Drugs
Comparator / control treatment
The placebo will be sterile normal saline (0.9% NaCl) for injection.
Control group
Placebo

Outcomes
Primary outcome [1] 301365 0
Safety assessments of ANB019 administration 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] 301365 0
Adverse events will be assessed continuously from the time of the first administration of IMP through to discharge from the study at the follow-up visit. ECGs will be performed during screening, on Day -1, Days 8, 15, 22 and 85.
Secondary outcome [1] 332438 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 ANB019 or its metabolite versus time data.
Timepoint [1] 332438 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, 1344 and 2016 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, 1344 and 2016 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, 24, 168, 336, 504, 840 and 1512 hours post last dose.
Secondary outcome [2] 332446 0
Presence of anti-drug antibodies measured with an immunoassay method to measure antibodies against ANB019 in human serum.
Timepoint [2] 332446 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 2016 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 1512 hours since the last dose administration.
Secondary outcome [3] 332447 0
ANB019 "ex vivo" inhibition of cytokine release (IL-8) upon IL-36 stimulation performed using whole blood collected from the participant.
Timepoint [3] 332447 0
For the SAD part, both SC and IV administration methods, whole blood will be collected for the IL-8 assay at the following time-points: Pre-Dose, 24, 168, 504, 1008, 1344 and 2016 hours Post-Dose.

For the MAD part, whole blood will be collected for the IL-8 assay at the following time-points: Pre-Dose, 168, 504 and 1512 hours.

Eligibility
Key inclusion criteria
For the healthy participants cohorts - healthy male and female as determined by a lack of clinically significant medical history, physical examination, ECGs, and clinical laboratory determinations.

For the plaques psoriasis cohort - male and female participants as determined by lack of clinically significant medical history other than clinically diagnosed moderate to severe plaque psoriasis.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Medical History and Concurrent Diseases:
a) Any significant acute or chronic medical illness.
b) Presence of any factors that would predispose the subject to develop infection e.g., rectal fissures, poor dentition, open skin lesions, and presence of pre-existing skin conditions that increase risks for injection site complications e.g. Behcet’s Disease, Psoriasis, pustular dermatoses.
c) Current or recent (within 3 months of study drug administration) gastrointestinal disease.
d) Previous administration of mAbs
2) Psoriasis Patients
a) Have concomitant dermatologic or medical condition(s) which may interfere with the investigator's ability to evaluate the subject's response to the study drug.
b) Have applied any topical medication (including corticosteroid, calcineurin inhibitor,topical H1 and H2 antihistamines, topical antimicrobials, other medicated topical agents) or herbal preparation within 21 days prior to Day -1.
c) Have received antibiotic treatment within 1 week prior to study entry.
d) Within 4 weeks prior to study entry, have received systemic treatment for psoriasis (including systemic corticosteroids, non-steroidals, immunosuppressants, or immunomodulating drugs) or treatment with UV light.
e) Have received any investigational drug or been part of any clinical trial within a period of three months or five half-lives (whichever is longer) prior to study entry.
f) Previous treatment with anti-tumour necrosis factor (TNF)/interleukin (IL-12/IL-23) and IL-17 or any other monoclonal antibodies is not allowed within 3 months or 5 half-lives or twice the duration of the biological effect of the product prior to Day -1.
3) 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.
4) Allergies and Adverse Drug Reaction
a) History of any significant drug allergy or reaction (such as anaphylaxis or hepatotoxicity) and reactivity to polysorbate 20 a component of ANB019 formulation, or the inactive ingredients (excipients)

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)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other
Other design features
This is an ascending dose study divided into three parts. The healthy participants 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 plaque psoriasis patients part and the healthy participants 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. The plaque psoriasis patients will be included in parallel with the healthy participants MAD cohorts.
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7608 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 15509 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 295839 0
Commercial sector/Industry
Name [1] 295839 0
AnaptysBio Pty Ltd
Address [1] 295839 0
Level 19, HWT Tower,
40 City Road,
Southbank,
Victoria, 3006
Country [1] 295839 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] 294689 0
Commercial sector/Industry
Name [1] 294689 0
CPR Pharma Services Pty Ltd
Address [1] 294689 0
28 Dalgleish Street,
Thebarton, Adelaide,
South Australia, 5031
Country [1] 294689 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297121 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 297121 0
192 Glen Osmond Road,
Eastwood, Adelaide,
South Australia 5063
Ethics committee country [1] 297121 0
Australia
Date submitted for ethics approval [1] 297121 0
29/11/2016
Approval date [1] 297121 0
31/01/2017
Ethics approval number [1] 297121 0
2016-11-811

Summary
Brief summary
This study will be conducted in three parts: the first part will investigate the effect of a single dose of ABN019 on healthy participants; the second part will investigate the effect of a single dose of ANB019 on psoriasis patients and the third part will investigate the effect of multiple (weekly) doses of ABN019 for 4 weeks on healthy participants. 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 psoriasis patient part and the multiple dose part of the study.
Over the entire study a total of 87 people will be enrolled over 10 dosing groups/ cohorts. In each group of 8 healthy participants, 6 will receive the active drug, ANB019 and the other 2 will receive an equivalent placebo (an injection/ infusion that looks identical to the active drug, but contains no active drug). In the psoriasis patient group, out of the 15 patients, 10 will receive the active drug, ANB019, and the remaining 5 will receive placebo.
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 ANB019 administered to healthy humans.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73046 0
Dr Jason Lickliter
Address 73046 0
Nucleus Network, The Burnet Tower, 5-th Floor,
89 Commercial Road,
Melbourne,
Victoria, 3004
Country 73046 0
Australia
Phone 73046 0
+61 3 90768960
Fax 73046 0
+61 3 90768911
Email 73046 0
J.Lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 73047 0
Dr Jason Lickliter
Address 73047 0
Nucleus Network, The Burnet Tower, 5-th Floor,
89 Commercial Road,
Melbourne,
Victoria, 3004
Country 73047 0
Australia
Phone 73047 0
+61 3 90768960
Fax 73047 0
+61 3 90768911
Email 73047 0
J.Lickliter@nucleusnetwork.com.a
Contact person for scientific queries
Name 73048 0
Dr Jason Lickliter
Address 73048 0
Nucleus Network, The Burnet Tower, 5-th Floor,
89 Commercial Road,
Melbourne,
Victoria, 3004
Country 73048 0
Australia
Phone 73048 0
+61 3 90768960
Fax 73048 0
+61 3 90768911
Email 73048 0
J.Lickliter@nucleusnetwork.com.a