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Trial registered on ANZCTR


Registration number
ACTRN12619000395134
Ethics application status
Approved
Date submitted
22/02/2019
Date registered
12/03/2019
Date last updated
11/02/2021
Date data sharing statement initially provided
12/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of the Safety, Pharmacokinetics and Efficacy of CBP-201 in adult patients with Atopic Dermatitis
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of the Safety, Pharmacokinetics and Preliminary Efficacy of CBP-201 in Adult Patients with Moderate to Severe Atopic Dermatitis
Secondary ID [1] 297330 0
CBP-201AU002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 311437 0
Condition category
Condition code
Skin 310076 310076 0 0
Dermatological conditions
Inflammatory and Immune System 310397 310397 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a Multiple Ascending Dose (MAD) study in adult patients who have been diagnosed with moderate to severe Atopic Dermatitis (AD). Thirty patients will be randomized at approximately 15 study sites. This research study is made up of the following parts: Screening Period, Baseline, Treatment Period and Follow-Up Period. Patients will be randomized to receive a Subcutaneous injection of either CBP-201 or placebo once a week for 4 doses. Each dose group will consist of 10 participants, with 8 participants receiving active study drug and 2 receiving matching placebo (8 active: 2 placebo). Three ascending dose levels are planned (75, 150 and 300 mg CBP-201). Patients will be followed for an additional 8 weeks for safety, efficacy and to further characterize the profile of CBP-201.
Adherence is managed by only giving injections in clinic.
Intervention code [1] 313586 0
Treatment: Drugs
Comparator / control treatment
Matching Placebo (Placebo is formulated as a solution containing identical excipients without antibody protein).
Control group
Placebo

Outcomes
Primary outcome [1] 318984 0
To evaluate the safety and tolerability profile of the CBP-201. Safety will be assessed by severity and frequency of the adverse events and serious adverse events. Clinically significant abnormalities in vital signs, laboratory samples, ECGs, and/or physical examination will be noted as adverse events and by evaluating the injection site.
Timepoint [1] 318984 0
Monitored during screening and throughout 11 weeks (EOS or Early Termination) after the last dose of the study treatment.
Secondary outcome [1] 366672 0
To evaluate the pharmacokinetics (PK) of CBP-201. Plasma CBP-201 concentrations will be summarized using descriptive statistics.
Timepoint [1] 366672 0
Blood sample for PK will be taken prior to study drug administration on dosing days. In addition, one PK sample will be taken on Day 29, 36, 50, 64 and 78 (or Early Termination). Plasma levels of CBP-201 are being measured for 84 days (12 weeks) following study drug administration to calculate standard PK parameters such as area under the curve (AUC), Cmax and Tmax.
Secondary outcome [2] 366673 0
To evaluate the clinical preliminary efficacy of CBP-201. Efficacy of CBP-201 is assessed by affected body surface area (BSA), the Eczema Area and Severity Index (EASI) and an Investigator’s Global Assessment (IGA) of disease severity.
Timepoint [2] 366673 0
Efficacy assessments will be measured during screening, baseline, Day 8, Day 15, Day 22, Day 29, Day 36, Day 50, Day 64 and Day 78 (End of Termination).
Several exploratory efficacy parameters and PRO measures will be evaluated for efficacy trends as follows:
• Percent change in EASI total score from Baseline to end of treatment (EOT) period
• Change in P-NRS from Baseline to EOT period
• Proportion of patients achieving greater than or equal to 2-point improvement in IGA from Baseline
• Change in affected BSA from Baseline
• Proportion of patients achieving greater than or equal to 3-point improvement in P-NRS from Baseline
• Proportion of patients achieving greater than or equal to 50% improvement in EASI from Baseline to EOT period
• Proportion of patients achieving greater than or equal to 75% improvement in EASI from Baseline to EOT period
• Proportion of patients achieving greater than or equal to 90% improvement in EASI from Baseline to EOT period
• Proportion of patients achieving IGA of 0 or 1 (clear; almost clear)
• Change from Baseline in DLQI to EOT period
Secondary outcome [3] 366674 0
To characterize the pharmacodynamic (PD) profile of multiple doses of CBP-201.
Timepoint [3] 366674 0
Blood sample for PD will be taken prior to study drug administration on dosing days. In addition, one PD sample will be taken on Day 29, 36, 50, 64 and 78 (or Early Termination). PD Parameters: Serum levels of IL-4, IL-13, IgE, TARC, LDH and in peripheral eosinophil counts will be measured. Additional PD parameters are LDH and peripheral eosinophil counts.

Eligibility
Key inclusion criteria
1. Patient able to read and understand, and willing to sign the informed consent form (ICF)
2. Male or female, aged 18 to 65 years (inclusive) at time of Screening
3. Willing and able to comply with clinic visits and study-related procedures
4. Have AD diagnosed by the Eichenfield revised criteria of Hannifin and Rajka, that has been present for at least 1 year before the Screening visit
5. Eczema Area and Severity Index (EASI) score greater than or equal to 12 at the Screening and Baseline visits
6. Investigator Global Assessment (IGA) score greater than or equal to 3 at the Screening and Baseline visits
7. Greater than or equal to 10% body surface area (BSA) of AD involvement at the Screening and Baseline visits
8. History of an inadequate response, in the judgement of the Investigator, to AD treatment with a topical regimen of corticosteroids, phosphodiesterase inhibitors or calcineurin inhibitors within 1 year of the Screening visit
9. Patients must have applied a bland emollient twice a day to affected areas for at least 7 days before the Baseline visit and be willing to continue for the duration of the study
10. Male patients must abstain from heterosexual activities or agree to use a condom through 90 days after the final dose of study drug. Women of child-bearing potential (WOCBP) must abstain from heterosexual activities or agree to use effective contraception.
Effective contraception for males and/or WOCBP includes:
a. Blockage methods – spermicides and condoms/spermicides and vaginal diaphragm for contraception, vaginal sponges or cervical cap (where available)
b. Oral contraceptives (“the pill”) for at least 1 month
c. Depot or injectable birth control or implantable contraception (e.g., Implanon)
d. Intrauterine device (IUD)
e. Documented evidence of surgical sterilization at least 6 months prior to Screening visit i.e., tubal ligation or hysterectomy for women or vasectomy for men
f. Women who are post-menopausal, as documented by measurement of follicle stimulating hormone (FSH)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of any of the following laboratory abnormalities at the Screening visit: a. White blood cell (WBC) below the lower limit of normal (LLN)
b. Neutrophil count below the LLN
c. Aspartate aminotransferase (AST) > 1.5 x the upper limit of normal (ULN)
d. Alanine aminotransferase (ALT) > 1.5 x the ULN
e. Creatine phosphokinase CPK >2ULN
f. Serum creatinine >1.2 ULN

2. Treatment with the following topical agents within 2 weeks before the Baseline visit: corticosteroids, phosphodiesterase inhibitors, tacrolimus or pimecrolimus
3. Systemic treatment for AD or for condition, with steroids or other immunosuppressive/ immunomodulating substances, e.g., cyclosporine, mycophenolate-mofetil, azathioprine or methotrexate within 4 weeks before the Baseline visit. Use of steroid inhalers and nasal corticosteroids is allowed.
4. Treatment with any cell depleting agents, e.g., rituximab, within 6 months of the Baseline visit or treatment with other biologics within 12 weeks of the Baseline visit
5. Prior treatment with dupilumab or any antibody against IL-4Ra or IL-13
6. Use of phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), tanning beds or any other light emitting device (LED), within 4 weeks before the Baseline visit
7. Two or more bleach baths within the 2 weeks before the Baseline visit
8. Treatment of AD with a prescription emollient (e.g., Atopiclair®, MimyX®, Epicerum®, etc.) within 2 weeks before the Baseline visit
9. Treatment with an investigational drug within 30 days or within 5 half-lives, whichever is longer, before the Baseline visit
10. Infection requiring treatment with oral or parenteral antibiotics, antivirals or systemic antifungals within 8 weeks before the Baseline visit
11. Superficial skin infections such as impetigo within 2 weeks before the Baseline visit
12. History of parasitic infection (e.g., helminth), within 6 months of the Baseline visit
13. History of vernal conjunctivitis
14. Known history of human immunodeficiency virus (HIV) infection
15. Positive results at the Screening visit for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody
16. Patients with positive QuantiFERON Gold test for tubercle bacillus (TB) at Screening
17. Treatment with a live (attenuated) vaccine within 8 weeks before the Baseline visit
18. History of malignancy within 5 years before the Baseline visit, with the following exceptions: patients with a history of completely treated carcinoma in situ of cervix, and non-metastatic squamous or basal cell carcinoma of the skin are allowed
19. Patients with a known allergy to L-histidine, Trehalose or Tween (polysorbate) 80
20. Planned surgical procedure during participation in this study
21. Use of a tanning booth/parlour within 4 weeks of Baseline
22. Women who are pregnant, planning to become pregnant or breast-feeding women
23. Any medical or psychiatric condition, laboratory or ECG parameter which, in the opinion of the Investigator or the Sponsor’s Medical Monitor, would place the patient at risk, interfere with participation in the study or interfere with the interpretation of study results.

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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/04/2019
Actual
3/05/2019
Date of last participant enrolment
Anticipated
27/09/2019
Actual
11/12/2019
Date of last data collection
Anticipated
10/12/2019
Actual
20/12/2019
Sample size
Target
30
Accrual to date
Final
31
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 13070 0
Veracity Clinical Research - Woolloongabba
Recruitment hospital [2] 13071 0
Sinclair Dermatology - East Melbourne
Recruitment hospital [3] 13072 0
Linear Clinical Research - Nedlands
Recruitment hospital [4] 14345 0
Fremantle Dermatology - Fremantle
Recruitment hospital [5] 14346 0
Peninsula Private Hospital - Kippa-Ring - Kippa-Ring
Recruitment hospital [6] 14347 0
East Sydney Doctors - Darlinghurst
Recruitment hospital [7] 14348 0
Novatrials - Kotara
Recruitment hospital [8] 14349 0
Paratus Clinical Pty Ltd Blacktown Trial Clinic - Blacktown
Recruitment hospital [9] 14350 0
Paratus Clinical Pty Ltd Kanwal Trial Clinic - Kanwal
Recruitment postcode(s) [1] 25578 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 25579 0
3002 - East Melbourne
Recruitment postcode(s) [3] 25580 0
6009 - Nedlands
Recruitment postcode(s) [4] 27348 0
6160 - Fremantle
Recruitment postcode(s) [5] 27349 0
4020 - Kippa-Ring
Recruitment postcode(s) [6] 27350 0
2010 - Darlinghurst
Recruitment postcode(s) [7] 27351 0
2289 - Kotara
Recruitment postcode(s) [8] 27352 0
2148 - Blacktown
Recruitment postcode(s) [9] 27353 0
2259 - Kanwal
Recruitment outside Australia
Country [1] 21267 0
New Zealand
State/province [1] 21267 0

Funding & Sponsors
Funding source category [1] 301893 0
Commercial sector/Industry
Name [1] 301893 0
Connect Biopharma Australia Pty Ltd
Country [1] 301893 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Connect Biopharma Australia Pty Ltd
Address
Suite 3 321-323 Chapel St.
Prahran, VIC 3181
Country
Australia
Secondary sponsor category [1] 301646 0
None
Name [1] 301646 0
Address [1] 301646 0
Country [1] 301646 0
Other collaborator category [1] 280530 0
Commercial sector/Industry
Name [1] 280530 0
Novotech (Australia) Pty Limited
Address [1] 280530 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 280530 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302583 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 302583 0
129 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 302583 0
Albania
Date submitted for ethics approval [1] 302583 0
06/02/2019
Approval date [1] 302583 0
28/03/2019
Ethics approval number [1] 302583 0

Summary
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple subcutaneous (SC) doses of CBP-201 in patients with moderate to severe Atopic Dermatitis.
Thirty patients will be randomized at approximately 10 study sites. This research study is made up of the following parts: Screening Period, Baseline, Treatment Period and Follow-Up Period. Patients will be randomized to receive either CBP-201 or placebo once a week for 4 doses. Each dose group will consist of 10 participants, with 8 participants receiving active study drug and 2 receiving matching placebo (8 active: 2 placebo). Three ascending dose levels are planned (75, 150 and 300 mg CBP-201). Patients will be followed for an additional 8 weeks for safety, efficacy and to further characterize the profile of CBP-201.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90722 0
Prof Rodney Sinclair
Address 90722 0
Sinclair Dermatology
Level 2, Wellington Pde
East Melbourne, VIC 3002
Country 90722 0
Australia
Phone 90722 0
+61 396542426
Fax 90722 0
Email 90722 0
[email protected]
Contact person for public queries
Name 90723 0
Daphne Craw
Address 90723 0
Novotech Australia Pty Ltd, Level 2, 381 MacArthur Ave Hamilton QLD 4007 AUSTRALIA
Country 90723 0
Australia
Phone 90723 0
+61 7 3137 6207
Fax 90723 0
Email 90723 0
[email protected]
Contact person for scientific queries
Name 90724 0
Daphne Craw
Address 90724 0
Novotech Australia Pty Ltd, Level 2, 381 MacArthur Ave Hamilton QLD 4007 AUSTRALIA
Country 90724 0
Australia
Phone 90724 0
+61 7 3137 6207
Fax 90724 0
Email 90724 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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