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Trial registered on ANZCTR


Registration number
ACTRN12620000700932
Ethics application status
Approved
Date submitted
22/04/2020
Date registered
25/06/2020
Date last updated
25/06/2020
Date data sharing statement initially provided
25/06/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase Ib study of ZL-1102 in mild-to-moderate psoriasis patients
Scientific title
A multi-center, double-blind, randomized, placebo-controlled, Phase Ib First-in-Human and Proof-of-Concept study to evaluate the safety, tolerability, and efficacy of a topical formulation of ZL-1102 in adults with mild-to-moderate chronic plaque psoriasis (CPP)
Secondary ID [1] 300596 0
ZL-1102-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Plaque Psoriasis 316341 0
Condition category
Condition code
Skin 314600 314600 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study consists of 2 Parts: Part A & Part B

Part A is open-label where subjects with CPP will receive a single topical treatment with ZL-1102 to a suitable psoriatic plaque followed by a 1-week observation period for safety/tolerability.
Subjects who are eligible for the study will report to study sites on Day 1 for baseline evaluations.
There will be pre-dose PK sampling and intensive PK sampling for 24 hours post-dose. After completion of the safety evaluation in Part A, and in the absence of findings that would trigger stop criteria, enrollment of subjects for Part B will be started
the dose of ZL-1102 administered: 2.3g/tube, recommended dosage to target plaque is approximately 0.15mg~0.3mg /cm2 [ZL-1102, 1% (w/w) Gel. Topical application should be based on the initial size of target plaque.

Part B
Part B is a double-blind, two-arm comparison of ZL-1102 Gel vs. Vehicle (placebo only). Approximately 44 subjects with CPP will be randomized in a 1:1 ratio to receive study medication of ZL-1102 Gel or Vehicle.

Part B will consist of a screening period, (Day -30 till Day -1), a 4-week treatment period during which study drug will be applied topically to a suitable psoriatic plaque, and a 2- week follow-up period.
study treatment: twice daily (BID)
the dose of ZL-1102 administered: 2.3g/tube, recommended dosage to target plaque is approximately 0.15mg~0.3mg /cm2 [ZL-1102, 1% (w/w) Gel. Topical application should be based on the initial size of target plaque.

The overall study duration is approximately 6 months (4.5 months recruitment plus 1.5 months study observation period).

Route of Administration is Topical
Dosage Formulation: gel
clinician or research nurse administers the gel.
adherence or fidelity will be assessed: in Part B, only the 1 tube each time study drug applied in clinic at D1, D8, D15 and D22. The weights should be recorded to the nearest 0.01gat minimum. And the subjects are trained to apply study drug as clinician or research nurse do, and record it in the patient diary.

frequency of administration in Part B: Study drug (ZL-1102 or matching placebo) will be applied twice daily for 28 days. No participants in Part A can participate in Part B.
Intervention code [1] 316912 0
Treatment: Drugs
Comparator / control treatment
ZL-1102 Gel Matching Placebo
Control group
Placebo

Outcomes
Primary outcome [1] 322947 0
To investigate the safety and tolerability of ZL-1102 of topical administration to plaques
in patients with Chronic Plaque Psoriasis.
Study part: Both parts

Outcome is assessed by vital signs, electrocardiograms (ECGs), and clinical laboratory assessments. Also by Treatment-emergent adverse events (TEAEs)

Timepoint [1] 322947 0
Screening period to EOT: from Day -1 to Day 43.
Part A: At Screening (up to 30 days prior to dosing), Day 1 and Day 8 post-dose administration.
Part B: At Screening (up to 30 days prior to dosing) then weekly from Day 1 to Day 29/EOT: on D1, D15, D22 and D29 and then at D43 (EOS) visit.

Secondary outcome [1] 380340 0
To investigate the efficacy of ZL-1102 hydrogel at Week 4 (Day 29) compared to Vehicle.
Study part: Both parts

Outcome is assessed by local PASI score of treated plaque
Timepoint [1] 380340 0
Efficacy measured using local PASI score of treated plaque at Week 4 (Day 29) from baseline of active treatment vs control.
Part A: At Screening (up to 30 days prior to dosing), Day 1 and Day 8 post-dose administration.
Part B: At Screening (up to 30 days prior to dosing) then weekly from Day 1 to Day 29/EOT: on D1, D15, D22 and D29 and then at D43 (EOS) visit.
Secondary outcome [2] 380341 0
To evaluate the PK profile of ZL-1102
Study part: Both parts. PK parameters Cmax, Tmax, AUC will be assessed, and the outcome is assessed by serum assay, urinalysis.
Timepoint [2] 380341 0
PK samples will be collected at Pre-dose, 0.5 hr post dose, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr on Day 1 in Part A.
PK samples will be collected in Part B at weekly clinic visits

Part B- Day 1, day 15, day 22, day 29, day 43
Secondary outcome [3] 380406 0
To evaluate the immunogenicity (ADA) during topical therapy with ZL-1102
Study part: Both parts.
outcome is assessed by skin biopsy
Timepoint [3] 380406 0
ADA samples will be collected at Predose, Post dose-D15, D22, D29(EoT) and on D43(EoS)
Part B only: At Screening (up to 30 days prior to dosing) then weekly from Day 1 to Day 29/EOT: on D1, D15, D22 and D29 and then at D43 (EOS) visit.

Eligibility
Key inclusion criteria
Subjects who meet ALL the following inclusion criteria are eligible for this study:
1. Signed and dated Informed Consent Form
2. Male or female subjects aged 18 to 75 years
3. Stable chronic mild-to-moderate plaque-type psoriasis at screening and baseline:
a. PASI less than or equal to 15 and
b. affected body surface area (BSA) less than or equal to 10% of total body area
4. Suitable psoriatic plaque (ALL criteria apply):
a. Lesion size: greater than 9 cm2 to 100 cm2
b. Lesion stable for greater than or equal to 3 months (by subject recall)
c. Lesional / local PASI score greater than or equal to 8
d. Plaque amenable to topical treatment, self-administration and not near the site(s) of venesection
5. Subject willing and able to avoid excess exposure to natural or artificial ultraviolet light
6. Negative pregnancy test (defined as negative serum pregnancy test at screening and negative urine pregnancy test prior to dosing on Day 1) for females of child-bearing potential (defined as pre-menopausal, less than 2 years post-menopausal, not surgically sterile). Details related to effective contraception are listed in the main protocol.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects who meet ANY of the following exclusion criteria are not eligible for participation:

1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis, palmar, plantar, scalp or nail disease) at screening
2. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium)
3. Ongoing use of topical or systemic treatments specified below and prior use of these therapeutics unless discontinued by interval as stated:
• Biological agents: 12 weeks
e.g., adalimumab, etanercept, infliximab, ustekinumab and others
• Other systemic immunomodulating therapies: 4 weeks
e.g., methotrexate, cyclosporine, fumaric acid (derivatives), systemic corticosteroids
• Photochemotherapy: 4 weeks
e.g., ultraviolet A with psoralen (PUVA)
• Phototherapy e.g., ultraviolet A (UVA) or ultraviolet B (UVB): 2 weeks
• Other investigational drugs: 4 weeks
(or 5 half-lives, whichever is longer)
• Topical therapies for CPP: 2 weeks
e.g., corticosteroids (TCS), vitamin D analogues, retinoids
4. Active systemic infections (other than common cold) or local infection of the suitable plaque to be treated during the 2 weeks prior to randomization
5. Positive test for HIV (HIV Ab), HBV (HBsAg or HBcAb or HBV DNA) or HCV (HCV RNA) at screening
6. History of hypersensitivity to any human or humanized biological agents judged as significant by the investigator
7. Any severe, progressive or uncontrolled medical or psychiatric condition at baseline that in the judgment of the investigator prevents participating in the study
8. Any clinically significant abnormal laboratory tests at screening (e.g. AST or ALT greater than 2 times ULN)
9. Inability or unwillingness to undergo repeated venipuncture and additionally (in Part B only) for skin biopsy
10. History or evidence of drug or alcohol abuse within 1 year prior to screening, as determined by history.
For Part A, a urine drug screen and alcohol breath test should be done at screening and Day -1 or done during screening within 48 hours of Day 1
For Part B, a urine drug screen should be done at screening.
Urine Drug Test includes all of the following: Amphetamines (AMP), Methamphetamines (MET), Methadone (MTD), Barbiturates (BAR), Benzodiazepines (BZO), Cocaine (COC), Opiates (OPI), Methyl enedioxy methamphetamine (MDMA), Phencyclidine (PCP), Tetrahydrocannabinol (THC)
11. Pregnant or nursing (lactating) women
12. Dementia or other neurological disease impairing understanding and compliance with treatment procedure. Visual, physical and any other impairments that interferes with a subject’s ability to complete study procedures and compliance with study protocol.
13. Subjects with confirmed malignancies, except for adequately treated in situ cervical carcinoma, or non-metastatic basal call or squamous cell carcinomas of the skin not involving or near the target lesion.
14. Subjects have live vaccine within 6 weeks prior to dosing on Day 1.
15. Subjects with active tuberculosis (TB) or untreated latent TB per local guidelines.
16. Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the administration schedule and study evaluations.
17. Subjects with prior exposure to ZL-1102.

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)
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
The study consists of 2 Parts: Part A & B.
Part A: All 6 subjects will receive a single topical application of ZL-1102 investigational product at the clinic on Day 1. The End of Study (EOS) visit occurs on Day 8. Part B: A total of 22 subjects will be randomized into each arm (44 subjects in total). The overall treatment duration is 28 days with a 14 day follow-up period. The EOS visit in Part B occurs on Day 43.
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
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] 16476 0
Sinclair Dermatology - East Melbourne
Recruitment postcode(s) [1] 30026 0
3002 - East Melbourne

Funding & Sponsors
Funding source category [1] 305017 0
Commercial sector/Industry
Name [1] 305017 0
Zai Lab (Shanghai) Co., Ltd.
Address [1] 305017 0
4/F, No.1 South Tower, 4560 Jinke Rd. Pilot Free Trade Zone (Shanghai), P.R. China, 201210
Country [1] 305017 0
China
Primary sponsor type
Commercial sector/Industry
Name
Zai Lab (Shanghai) Co., Ltd.
Address
4/F, No.1 South Tower, 4560 Jinke Rd. Pilot Free Trade Zone (Shanghai), P.R. China, 201210
Country
China
Secondary sponsor category [1] 305375 0
None
Name [1] 305375 0
Address [1] 305375 0
Country [1] 305375 0
Other collaborator category [1] 281215 0
Commercial sector/Industry
Name [1] 281215 0
Novotech (Australia) Pty Limited
Address [1] 281215 0
Level 2, 235 Pyrmont Street, Pyrmont NSW 2009 Australia
Country [1] 281215 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305413 0
Bellberry Limited HREC
Ethics committee address [1] 305413 0
123 Glen Osmond Road, Eastwood SA 5063, Australia
Ethics committee country [1] 305413 0
Australia
Date submitted for ethics approval [1] 305413 0
19/02/2020
Approval date [1] 305413 0
01/05/2020
Ethics approval number [1] 305413 0

Summary
Brief summary
This is a Phase Ib study to investigate the safety, tolerability, efficacy and PK of ZL-1102 in subjects with mild-to-moderate chronic plaque psoriasis (CPP).
The study consists of 2 Parts:
Part A
Part A is open-label. After a 30-day screening period, six (6) subjects with CPP will receive a single topical treatment with ZL-1102 to a suitable psoriatic plaque followed by a 1-week observation period for safety/tolerability.
Part B
Part B is a double-blind, two-arm comparison of ZL-1102 Gel vs. Vehicle (placebo only). Approximately 44 subjects with CPP will be randomized in a 1:1 ratio to receive study medication of ZL-1102 Gel or Vehicle.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100298 0
Prof Rodney Sinclair
Address 100298 0
Sinclair Dermatology,
2 Wellington Parade, East,
Melbourne VIC 3002,
Australia
Country 100298 0
Australia
Phone 100298 0
+61 390130099
Fax 100298 0
Email 100298 0
rsinclair.clinicaltrials@sinclairdermatology.com.au
Contact person for public queries
Name 100299 0
Ms Lanna Chen
Address 100299 0
Sr. Director, Clinical Project Management,
Zai Lab (Shanghai) Co., Ltd
4560 Jinke Road, Jinchuang Plaza Bldg 1, 4/F, Pudong, Shanghai, China 201210
Country 100299 0
China
Phone 100299 0
+86 13818103207
Fax 100299 0
Email 100299 0
lanna.chen@zailaboratory.com
Contact person for scientific queries
Name 100300 0
Ms Bei Qi
Address 100300 0
Medical Director,
Zai Lab (Shanghai) Co., Ltd
4560 Jinke Road, Jinchuang Plaza Bldg 1, 4/F, Pudong, Shanghai, China 201210
Country 100300 0
China
Phone 100300 0
+86 15502159521
Fax 100300 0
Email 100300 0
bei.qi@zailaboratory.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not applicable
What supporting documents are/will be available?
No other documents available
Summary results
No Results