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Trial registered on ANZCTR


Registration number
ACTRN12618000756224
Ethics application status
Approved
Date submitted
30/04/2018
Date registered
4/05/2018
Date last updated
9/01/2019
Date data sharing statement initially provided
9/01/2019
Date results information initially provided
9/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety, tolerability, pharmacokinetics and pharmacodynamics of CBP-201 in healthy volunteers
Scientific title
A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CBP-201 Administered to Healthy Adult Subjects
Secondary ID [1] 294735 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 307619 0
Condition category
Condition code
Inflammatory and Immune System 306675 306675 0 0
Other inflammatory or immune system disorders
Skin 306748 306748 0 0
Dermatological conditions
Skin 306749 306749 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will enroll 5 cohorts of subjects who will be randomized to receive a single dose of CBP-201 or placebo. Four of the 5 cohorts will receive study drug via subcutaneous administration. The 5th cohort will receive drug via intravenous injection.

Subjects will receive a single dose of CBP-201 or matching placebo administered by subcutaneous injection at a planned dose level of 75 mg, 150 mg, 300 mg or 600 mg (cohorts 1- 4 respectively). Cohort 5 will receive 300 mg of CBP-201 or placebo via intravenous injection.

Each cohort will enroll 8 subjects, 6 to receive active and 2 to receive placebo. Sentinel subjects will be used with the initial cohort and with all dose escalations. If dosing
of this sentinel participants proceed without clinically-significant adverse events (AEs) (as adjudicated by the Safety Monitoring Committee [SMC]), the remaining participants will be dosed.

All subjects will remain under observation in the clinical center for 24 hours after receiving study drug to allow for PK sample collection, to assess for adverse events (AEs) and injection site reactions.
After the last enrolled subject at a given dose level has completed Visit 4 (Day 15), the available blinded safety/tolerability data for that cohort will be reviewed by a Safety Review Committee (SRC) The SRC will determine if is safe to escalate to the next dose group. If all 5 cohorts are dosed, a total of 40 subjects will be enrolled (30 active; 10 placebo).

Study duration will be for approximately 105 days or 113 if optional visit to only collect blood is required (30 days screening; 1 day for treatment, and 12 weeks post treatment follow-up plus the potential additional visit on Day 113).

Screening will take place from day -30 to day -1. The study will be explained and participants will be asked to provide informed consent. Following consent, each potential subject will be examined before the start of the study to determine their eligibility for participation, including review of medical history and eligibility as per the inclusion/ exclusion criteria.

Participants will be confined to the clinic from day -1 to day 2, with single dose administered on day 1. Subjects will receive their study injection in the morning of day 1, and will remain in the clinical centre for observation for the following 24 hour period.
Blood samples will be taken at baseline and at various timepoints post dose throughout the day. Vital signs will be recorded every 15 mins for 1 hour post dose, and then every 4 hours. A post injection ECG will also be performed.

Post treatment follow up visits will be conducted on day 2 before the subject is discharged, then subsequently as an outpatient on days 4,8,11,15,22,29,43,57 and 85.

The follow up visits will record adverse events and concomitant meds, vital signs will be reviewed in addition to review of injection site findings. Bloods will be collected for safety and for pharmacokinetic and pharmacodynamics analysis. A 12-lead ECG will also be performed.

There will be an optional day 113 PK visit which may be required to obtain a blood sample

Intervention code [1] 301027 0
Treatment: Drugs
Comparator / control treatment
There will be participants on placebo in each cohort (treatment assignment will be double- blinded). The injection received by the placebo patients will be without the CBP-201 active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 305681 0
Composite primary outcome Safety and tolerability of escalating doses of CBP-201. This will be assessed on basis of adverse events reported, vital signs, ECG, injection site evaluations, safety laboratory parameters including anti- drug antibodies (ADA).

There may be adverse events (AEs) at the site of injection that include bruising, inflammation, local pain or bleeding. Other AEs may include an allergic reaction to the medication which may include fever, itching, difficulty breathing and changes in blood pressure.



Timepoint [1] 305681 0
Safety will be assessed at baseline, post dose at day 1 and day 2 whilst in confinement, and on days 4,8,11,15,22,29,43,57 and 85 (after participants are discharged).

Vital signs (temperature, respiratory rate, BP, HR) will be recorded pre-dose on Day 1, and every 15 minutes for 1hour post-dose and then every 4 hours up to day 2. On other visits, this will be performed once.
ECG will be obtained pre-dose and 12 hours post-dose (+/- 30mins). On other visits, a single ECG will be obtained.
The injection site will be assessed post injection on day 1 , 2 and on days 4,8,11,15,22 and 29.
Blood samples for ADA will be taken once pre-dose on day 1 at -30mins and once on day 29,57 and 85.
Bloods for safety parameters will be taken on during once during screening, day 1 -30 mins, and post dose on days 4,8,11,15, 22, 29, 43, 57 and 85.
Secondary outcome [1] 346156 0
Plasma concentration and pharmacokinetic parameters including maximum concentration (Cmax), time to maximum concentration (Tmax) and Half-life (t1/2).
Timepoint [1] 346156 0
Pharmacokinetics will be assessed at baseline at day 1, -30 mins, then post dose at 1 hour, 2 hours, 4 hours , 8 hours, 12 hours , and 24 hours post dose, then days 4,8,11,15,22,29,43, 57,and 85, with an optional visit on day 113.
Secondary outcome [2] 346157 0
Evaluate the pharmacodynamic (PD) profile of CBP-201 as determined by blood levels of IL-4, IL-13, IgE, and thymus activation regulated chemokine (TARC).
Timepoint [2] 346157 0
Pharmacodynamics will be assessed at baseline at day 1, -30 mins, then post dose at 24 hours post dose, then days 4,8,11,15,22,29,43, 57,and 85.

Eligibility
Key inclusion criteria
• Healthy male and female subjects age between 18 and 65 years, inclusive
• Able to provide written informed consent prior to any study procedures
• Male subjects must abstain from heterosexual activities or agree to use an adequate method of contraception through 90 days after the dose of study drug. Heterosexual women of child-bearing potential (WOCBP) who are sexually active must be willing to use effective contraception. Effective contraception includes:
• Using a condom, and a diaphragm or cervical cap
• Oral contraceptives (The Pill)
• Depot or injectable birth control or implantable contraception (e.g. Implanon)
• IUD (intrauterine device)
• 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.

Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects presenting with any of the following will not be included in the study:
• Any clinically significant laboratory abnormalities on screening as determined by the investigator
• Acute illness or history of illness, which in the opinion of the investigator could pose a threat or harm to the subject or obscure interpretation of laboratory tests or interpretation of study data. Subjects with chronic illness such as diabetes, heart disease, renal insufficiency, asthma, chronic pain, an immunocompromised state or substance abuse are specifically excluded
• Positive pregnancy test
• Women who are pregnant, considering becoming pregnant or nursing
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV)
• Positive Quantiferon Gold Test
• Positive screen for illicit substances and alcohol
• Subjects with known allergy or hypersensitivity to any components of the study drug
• Subjects who have received a live vaccine within 3 months of study entry
• Subjects regularly taking medication for a chronic condition. However, hormonal contraception and paracetamol, less than 2g per day, is allowed
• Subjects currently participating in an interventional study must wash out of the previous study for at least 30 days or 5 half-lives of the study drug, whichever is longer
• Planned surgical procedure during the study participation period

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)
Randomisation Lists will be prepared for each cohort and issued as appropriate to facilitate randomised Subject treatment.
This will be issued prior to dosing of the first subject and provided to the site pharmacy. The site pharmacy is unblinded and will dispense investigational drug in accordance with the allocation sequence disclosed in the randomization list.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created using SAS software package
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
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
A detailed Statistical Analysis Plan will be prepared for approval by the Sponsor prior to clinical database lock.
There is currently no clinical information about CBP-201. The sample size for safety evaluation was determined based on experience from other initial clinical safety studies based for other monoclonal antibodies against IL-4Ra. Sample size chosen is for the purpose of the study.
Safety Analysis Set: All participants who received any amount of study drug.
PK Analysis Set: All participants who received study drug (CBP-201 ) and have sufficient PK data for analysis.
PD Analysis Set: All participants who received study drug (CBP-201) and have sufficient PD data for 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] 10800 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 22540 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 299343 0
Commercial sector/Industry
Name [1] 299343 0
Connect Biopharma Australia Pty Ltd
Address [1] 299343 0
Suite 3 321-323 Chapel St.
Prahran,
VIC 3181
Australia
Country [1] 299343 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Connect Biopharma Australia Pty Ltd
Address
Suite 3 321-323 Chapel St.
Prahran,
VIC 3181
Australia
Country
Australia
Secondary sponsor category [1] 298613 0
Commercial sector/Industry
Name [1] 298613 0
Clinical Network Services (CNS) Pty Ltd
Address [1] 298613 0
Level 4, 88Jephson Street
Toowong, QLD 4066
Australia
Country [1] 298613 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300249 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 300249 0
Office of Ethic & Research Governance
Level 5/553 St Kilda Rd
Melbourne VIC 3004
Australia
Ethics committee country [1] 300249 0
Australia
Date submitted for ethics approval [1] 300249 0
01/05/2018
Approval date [1] 300249 0
09/06/2018
Ethics approval number [1] 300249 0

Summary
Brief summary
The primary aims of this first-in-human study are to investigate the safety and tolerability of CBP-201. The secondary aim is to investigate the pharmacokinetics and pharmacodynamics of CBP-201 related to contact pathway activation.
Up to 40 participants will be recruited to five Cohorts of 8 participants each in this double-blind study.
Participants in Cohort 1 will be randomized to receive an subcutaneous injection of 75 mg of CBP-201 (6 participants) or placebo (2 participants). Two sentinel participants (one allocated to placebo and one allocated to CBP-201) will be dosed initially. If dosing of these sentinel participant proceeds without clinically-significant adverse events (AEs) over a defined period (as adjudicated by a Safety Monitoring Committee), the remaining participants will be dosed.
Cohorts 2-4 will be analogous to Cohort 1 in terms of study procedures. The dose level will be established following assessment of safety and PK data of the preceding cohorts but is planned to increase to 150mg (cohort 2), 300mg (cohort 3) or 600mg (cohort 4).
An additional cohort (5) will receive 300mg of CBP-201 or placebo via IV injection instead of subcutaneous injection but all other study procedures will be the same of previous cohorts.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83046 0
Dr Ben Snyder
Address 83046 0
Nucleus Network
Level 5 Burnet Tower, 89 Commercial Rd
Melbourne VIC 3004


Country 83046 0
Australia
Phone 83046 0
+613 9076 8960
Fax 83046 0
+61 3 9076 8911
Email 83046 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 83047 0
Dr Ben Snyder
Address 83047 0
Nucleus Network
Level 5 Burnet Tower, 89 Commercial Rd
Melbourne VIC 3004


Country 83047 0
Australia
Phone 83047 0
+613 9076 8960
Fax 83047 0
+61 3 9076 8911
Email 83047 0
b.snyder@nucleusnetwork.com.au
Contact person for scientific queries
Name 83048 0
Dr Jeffery White
Address 83048 0
Suzhou Connect Biopharmaceuticals, Ltd.
Science and Technology Park
Building 2, 3rd Floor
6 Beijing West Road
215400 Taicang, Jiansu, China



Country 83048 0
China
Phone 83048 0
+86 0512-53577866
Fax 83048 0
Email 83048 0
jwhite@connectpharm.com

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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary