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Trial registered on ANZCTR


Registration number
ACTRN12622000344796
Ethics application status
Approved
Date submitted
19/02/2022
Date registered
24/02/2022
Date last updated
28/01/2024
Date data sharing statement initially provided
24/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1/1b, Three-Part, Randomised, Placebo-Controlled, Single- and Multiple-Ascending-Dose Studyto Evaluate the Safety, Pharmacokinetics, and Activity of SZN-1326 in Healthy Volunteers and in Subjects with Moderate to Severe Ulcerative Colitis
Scientific title
A Phase 1/1b, Three-Part, Randomised, Placebo-Controlled, Single- and Multiple-Ascending-Dose Studyto Evaluate the Safety, Pharmacokinetics, and Activity of SZN-1326 in Healthy Volunteers and in Subjects with Moderate to Severe Ulcerative Colitis
Secondary ID [1] 306482 0
CL-1326-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 325341 0
Condition category
Condition code
Inflammatory and Immune System 322726 322726 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part 1: Single dose of SZN-1326 via intravenous injection, or subcutaneous injection. Each dose level will be tested within one cohort. Each patient will only be assigned one dose level. Dose cohorts will progress through 25mg IV, 2.5mg IV, .01mg IV, 04mg IV, .1mg IV/SC, .4mg IV/SC, 1mg IV/SC, and two additional doses whose concentration will be determined based on data from the prior cohorts. Progression between cohorts will commence based upon recommendation of the SRC based on its review of safety data after all patients in the preceding cohort have been observed for at least 14 days after dose. All dosing is performed while patients are confined in the clinical trial unit for a period prior and after dosing.

Part 2: Multiple Ascending Dose - Healthy Volunteers: Multiple doses of SZN-1326 for a period of 4 weeks via weekly intravenous injection . Part 2 may commence upon recommendation of the SRC based on its review of all safety data available when patients in dose cohort .4mg have been observed for 14 days after last dose. Each patient will only be assigned one dose level. 3 dose cohorts will be tested starting at .1mg and progressing to the highest dose concentration based on data from the SAD, with route of administration also determined by data in the SAD. All dosing is performed while patients are confined in the clinical trial unit for a period prior and after dosing.
Intervention code [1] 322905 0
Treatment: Drugs
Comparator / control treatment
Placebo will be in the form of normal saline (0.9% solution for injection), administered in the same manner and with the same volume as the study drug for the given cohort.
Control group
Placebo

Outcomes
Primary outcome [1] 330528 0
Part 1 and 2: Safety and tolerability of SZN-1326 in HVs, based on the frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), electrocardiograms (ECGs), treatment-emergent laboratory and physical examination findings. Adverse events may include reactions to study drug, injection or infusion site reactions, etc. Events will be assessed based on investigator observation and patient self report. AEs will be graded in accordance with CTCAE criteria.
Timepoint [1] 330528 0
Part 1: The safety observations of all types that are assessed by the investigator or reported by the site will be assessed at least every other week, with TEAEs and TESEAs assessed at every contact with the subject until 4 weeks post dose.
Part 2: tThe safety observations of all types that are assessed by the investigator or reported by the site will be assessed at least every other week, with TEAEs and TESEAs assessed at every contact with the subject until 4 weeks post last dose.
Primary outcome [2] 330529 0
Parts 1 and 2: The maximum tolerated dose (MTD) of SZN-1326 in HVs, per route of administration (IV or SC)
Timepoint [2] 330529 0
Part 1 and 2: MTD will be defined by the dose cohort below which 2 or more subjects have an SZN-1326-related TEAE (NCI CTCAE is equal to or greater than grade 3) occurring within 14 days of the last study drug administration.
Secondary outcome [1] 406530 0
Part 1: Pharmacokinetic parameters (tested from blood serum) in HVs following single dose of SZN-1326. Parameters assessed will include but are not limited to Cmax, Clast, Tmax, AUC0-last, AUC0-inf, CL, t½,, etc. as available data allow.
Part 2: Pharmacokinetic parameters (tested from blood serum) in HVs following multiple dose of SZN-1326. Parameters assessed will include but are not limited to Cmax, Clast, Ctau, Tmax, AUC0-last, AUCtau, AUC0-inf, CL, CLss, t½,, etc. as available data allow.
Timepoint [1] 406530 0
Part 1 (IV): PK will be measured on Day 0 (day of dosing) once pre-dose, and post-dose (end of administration) at 5 min (± 5 minutes), 30 mins (±5 minutes), 2 hours (±5 minutes), 4 hours (±10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes). Then on day 1, 2, 4, 7, 10, 14, 21, and 28.

Part 1 (SC): PK will be measured on Day 0 (day of dosing), once pre-dose and post-dose (end of administration): 5 min (± 5 mins), 30 mins (±5 mins), 2 hours (±5 mins), 4 hours (± 10 mins), 8 hours (± 10 mins), 12 hours (± 10 mins), then on Day 1, 2, 4, 7, 10, 14, 21, and 28.

Part 2: PK will be measured on Day 0 (day of dosing), once pre-dose and post-dose (end of administration): 5 min (± 5 mins), 30 mins (±5 mins), 2 hours (±5 mins), four hours (±10 mins), 8 hours (± 10 mins), 12 hours (± 10 minutes), then on Day 1, 2, 4, 7, 14, 21, 22, 23, 25, 28, 31, 35, and 56.
Secondary outcome [2] 406531 0
Prevalence of Anti-drug Antibodies (ADA) as measured in blood serum for SZN-1326 at baseline and incidence of ADA during the study.
Timepoint [2] 406531 0
Part 1 (IV and SC): ADA will be measured on Day 0 (day of dosing) once pre-dose, and at Day 14 and 28.
Part 2: ADA will be measured on Day 0 (day of dosing) once pre-dose, and at Day 7, 14, 21, 28 and 56.

Eligibility
Key inclusion criteria
1. Be a healthy male or female adult.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Is pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
2. Has previously received antibody or biologic therapy whether licensed or investigational (immunoglobulin products, monoclonal antibodies or antibody fragments) within the past 6 months.
3. Has received treatment with any experimental drug within 30 days prior, or within five half-lives, prior to Day 0 visit (Baseline), whichever is longer.
4. Has a history of hyperthyroidism, Paget’s disease, osteomalacia, or a fracture within 4 weeks of Screening.
5. Has a history of a previous severe allergic reaction with generalized urticaria, angioedema or anaphylaxis.
6. Has clinically significant abnormalities on ECG.
7. A QT duration corrected for heart rate by Fridericia's formula (QTcF) >450 msec for males and >470 msec for females based on either single or averaged QTcF values of triplicate?ECGs prior to study drug administration (Part 1 only)
8. Has a history of malignant neoplasm, except for adequately treated non-metastatic basal or squamous cell cancers of the skin (>1 year ago) or carcinoma in situ of the uterine cervix (>3 years ago) that has been fully treated and shows no evidence of recurrence. Subjects under evaluation for possible malignancy are not eligible.
9. Has a first degree relative with colorectal cancer.

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)
A randomisation and trial supply management system (RTSM) will manage the randomisation of eligible study subjects. Treatment assignment will not be known to the investigators or patients.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation.
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
Participants are assigned to one cohort, defined by dose and administration type. Dose cohorts are completely enrolled prior to the next cohort. Cohorts at the same dose but different mode of administration in Part 1 may enroll in parallel. Otherwise dose cohorts are enrolled sequentially such that the next higher dose is enrolled only once enrollment and observation has completed in the previous cohort. Part 2 will run independently once open from Part 1, but in the same fashion.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size for this study is based on dose escalation rules and not based on any statistical criteria.

Statistical analyses will be descriptive in nature. Summaries will be provided for subject disposition, demographics, baseline characteristics, safety, PK, PD, and ADA parameters and presented by cohort and treatment group.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/05/2022
Actual
9/05/2022
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
9/03/2024
Actual
Sample size
Target
68
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 310829 0
Commercial sector/Industry
Name [1] 310829 0
Surrozen Operating, Inc.
Country [1] 310829 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Surrozen Operating, Inc.
Address
171 Oyster Point Boulevard, Suite 400
South San Francisco, CA 94080
United States
Country
United States of America
Secondary sponsor category [1] 312078 0
Commercial sector/Industry
Name [1] 312078 0
Novotech (Australia) Pty Limited
Address [1] 312078 0
Level 3, 235 Pyrmont Street
Pyrmont NSW 2009
Australia
Country [1] 312078 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310393 0
Alfred Health HREC
Ethics committee address [1] 310393 0
Ethics committee country [1] 310393 0
Australia
Date submitted for ethics approval [1] 310393 0
02/03/2022
Approval date [1] 310393 0
28/03/2022
Ethics approval number [1] 310393 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117502 0
Dr Christopher Argent
Address 117502 0
Scientia Clinical Research
Bright Building, Level 5, Corner High & Avoca Street
Randwick NSW 2031
Country 117502 0
Australia
Phone 117502 0
+61 02 9382 5844
Fax 117502 0
Email 117502 0
[email protected]
Contact person for public queries
Name 117503 0
Christopher Argent
Address 117503 0
Scientia Clinical Research
Bright Building, Level 5, Corner High & Avoca Street
Randwick NSW 2031
Country 117503 0
Australia
Phone 117503 0
+61 02 9382 5844
Fax 117503 0
Email 117503 0
[email protected]
Contact person for scientific queries
Name 117504 0
Christopher Argent
Address 117504 0
Scientia Clinical Research
Bright Building, Level 5, Corner High & Avoca Street
Randwick NSW 2031
Country 117504 0
Australia
Phone 117504 0
+61 02 9382 5844
Fax 117504 0
Email 117504 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
Privacy and Intellectual property considerations


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.