Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001449729
Ethics application status
Approved
Date submitted
27/09/2022
Date registered
14/11/2022
Date last updated
23/06/2024
Date data sharing statement initially provided
14/11/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomized, Double-blind, Placebo-controlled Phase I Study of Subcutaneous EQ102 Administered in a Single and Multiple Ascending Dose Schedule
Scientific title
A Randomized, Double-blind, Placebo-controlled Phase I Study to assess the safety and tolerability of Subcutaneous EQ102 Administered in a Single and Multiple Ascending Dose Schedule.
Secondary ID [1] 307543 0
EQ102-105-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Celiac Disease 326977 0
Condition category
Condition code
Inflammatory and Immune System 324167 324167 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a First in Human, randomized, double-blind, placebo-controlled study of EQ102 administered via subcutaneous (SC) injection as single (SAD) or multiple (MAD) doses. In Part A (SAD), up to approximately 48 healthy adult men and women will be enrolled and randomized to 6 cohorts (n=8 per cohort) to receive single ascending doses of EQ102 SC at doses of 50, 100, 200, 500 or up to 1000 mg or placebo. Specific dose levels for each cohort will be agreed by SRC prior to commencement of dosing in that cohort. Additional Part A cohort(s) may be added to achieve the study's objectives with agreement by the SRC. Dosing in each cohort for Part A will commence with two sentinel participants with one of the two sentinels randomized to receive EQ102 SC and the other randomized to receive placebo SC. EQ102 will be given SC in sequential, escalating doses contingent on a review of safety, tolerability, and available PK data of the previous dose level by a Safety Review Committee (SRC).

In Part B (MAD), healthy adult volunteers will be enrolled and randomized to 3 cohorts (n=8 per cohort) to receive multiple ascending doses of EQ102 or placebo SC. In Part B, up to three dose levels will be evaluated in healthy volunteers. The starting dose for Part B will be based on review of safety and PK data from Part A. A single dose of EQ102 (or placebo) will be administered SC once per week, for a total of 4 weeks (4 doses of EQ102 or placebo SC). The decision to escalate between dose levels will be based upon review of all safety and PK data.

Subcutaneous injection of EQ102 or placebo will be administered by clinical staff, per protocol.

Adherence to the intervention will be done via completion of drug accountability.
Intervention code [1] 324003 0
Treatment: Drugs
Comparator / control treatment
Placebo for EQ102 will be sterile normal saline for injection.
Control group
Placebo

Outcomes
Primary outcome [1] 331981 0
To assess the safety and tolerability of EQ102 after single ascending subcutaneous (SC) doses by incidence of treatment-emergent adverse events (TEAEs), Changes in vital sign measurements, Changes in electrocardiogram (ECG) parameters, Changes in clinical laboratory results
Timepoint [1] 331981 0
Adverse Events: graded using the National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5). Assessed daily at Screening, Day -1 (Admission), Day 1 Pre-dose and Post-dose, Day 2, Day 3, Day 4, Day 6, Day 8 (Discharge), Day 15, Day 22, Day 29, Day 36 and Day 43 (End of Study) and Early Termination Visit.

Vital signs assessments to include blood pressure (sphygmomanometer), pulse (pulse oximeter), respiratory rate (manual breath count), and oral temperature (digital thermometer). Assessed at: Screening, Day -1, Day 1 Pre-dose, On-dosing, 2 hrs, 6 hrs and 8 hrs post-dose, Days 2 and 3 at 24 hrs (Day 2) and 48 hrs (Day 3) post-dose, Day 4, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43 (End of Study) and Early Termination Visit.

12-Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day -1, Day 1 Pre-dose, On-dosing, 2hrs, 4hrs, 8hrs and 12 hrs post-dose, Day 2 24 hrs post-dose, Day 4 72 hrs post-dose, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43 (End of Study) and Early Termination Visit.

Clinical Laboratory Evaluations (clinical chemistry, haematology and urinalysis): Blood and urine samples collected at Screening, Day -1, Day 2 24 hrs post-dose, Day 4, Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43 (End of Study) and Early Termination Visit.
Primary outcome [2] 331982 0
To assess the safety and tolerability of EQ102 after multiple ascending SC doses by Incidence of TEAEs, Changes in vital sign measurements, Changes in electrocardiogram (ECG) parameters, Changes in clinical laboratory results
Timepoint [2] 331982 0
Adverse Events: graded using the National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5). Assessed daily at Screening, Day -1 (Admission), Day 1, Day 2 (Discharge), Day 4, Day 6, Day 7 (Admission), Day 8 (Discharge), Day 14 (Admission), Day 15 (Discharge), Day 21 (Admission), Day 22, Day 23 (Discharge), Day 25, Day 27, Day 29, Day 36, Day 43, Day 50, Day 57 and Day 64 (End of Study) and Early Termination Visit.

Vital signs assessments to include blood pressure (sphygmomanometer), pulse (pulse oximeter), respiratory rate (manual breath count), and oral temperature (digital thermometer). Assessed at: Screening, Day -1, Day 1 pre-dose, 2 hrs, 6 hrs and 8 hrs post-dose, Day 2, Day 4, Day 6, Day 7, Day 8 pre-dose, 2 hrs, 6 hrs, 8 hrs post-dose, Day 14, Day 15 pre-dose, 2 hrs, 6 hrs, 8 hrs post-dose, Day 21, Day 22 pre-dose, 2 hrs, 6 hrs, 8 hrs post-dose, Day 23, Day 25, Day 27, Day 29, Day 36, Day 43, Day 50, Day 57 and Day 64 (End of Study) and Early Termination Visit.

12-Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day -1, Day 1 Pre-dose, On-dosing, 2 hrs, 4hrs, 8hrs and 12 hrs post-dose, Day 2 24 hrs post-dose, Day 4 72 hrs post-dose, Day 6, Day 8 pre-dose, Day 15 pre-dose, Day 22 pre-dose, On-dosing, 2 hrs, 4 hrs, 8hrs and 12 hrs post-dose, Day 23 24 hrs post-dose, Day 25 72 hrs post-dose, Day 27, Day 29, Day 36, Day 43, Day 50, Day 57 and Day 64 (End of Study) and Early Termination Visit.

Clinical Laboratory Evaluations (clinical chemistry, haematology and urinalysis): Blood and urine samples collected at Screening, Day -1, Day 2 24 hrs post-dose, Day 4, Day 7, Day 14, Day 21, Day 23, Day 29, Day 36 and Day 43, Day 50, Day 57, and Day 64 (End of Study) and Early Termination Visit.
Secondary outcome [1] 411801 0
To assess the Pharmacokinetics (PK) of EQ102 after single ascending SC doses.
PK parameters to be calculated include (but are not limited to):
• Maximum observed concentration (Cmax)
• Time to Cmax (Tmax)
• Area under the concentration-time curve (AUC0-t)
• Area under the concentration time curve from time zero extrapolated to infinity (AUC0-inf)
• Apparent terminal elimination half-life (t1/2)
• Volume of distribution (Vd)
Timepoint [1] 411801 0
Plasma PK samples will be collected as follows:

Day 1 Pre-dose, On-dosing, 2 hrs, 4 hrs and 8 hrs, 12 hours post-dose, Day 2 24 hrs post-dose, Day 4 72 hrs post-dose, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43 (End of Study) and Early Termination Visit.
Secondary outcome [2] 411802 0
To assess the Pharmacokinetics (PK) of EQ102 after multiple ascending SC doses.
PK parameters to be calculated include (but are not limited to):
• Maximum observed concentration (Cmax)
• Time to Cmax (Tmax)
• Area under the concentration-time curve (AUC0-t)
• Area under the concentration versus time curve for the dosing interval (AUC0–tau)
• Area under the concentration time curve from time zero extrapolated to infinity (AUC0-inf)
• Apparent terminal elimination half-life (t1/2)
• Volume of distribution (Vd)
• Accumulation ratio for Cmax and AUC0-t using the first and last dose
Timepoint [2] 411802 0
Plasma PK samples will be collected as follows:

Day 1 Pre-dose, On-dosing, 2 hrs, 4 hrs and 8 hrs, 12 hours post-dose, Day 2 24 hrs post-dose, Day 4 72 hrs post-dose, Day 6 120 hours post-dose, Day 8 Pre-dose, Day 15 Pre-dose, Day 22 Pre-dose, On-dosing, 2 hrs, 4 hrs and 8 hrs, 12 hours post-dose, Day 23 24 hrs post-dose, Day 25 72 hrs post-dose, Day 27, Day 29, Day 36, Day 43, Day 50, Day 57, and Day 64 (End of Study) and Early Termination Visit.
Secondary outcome [3] 411803 0
To assess the immunogenicity of EQ102 after single ascending SC doses.
Composite Immunogenicity endpoints include:
• Incidence of EQ102 ADA (anti-drug antibody)
• Incidence of neutralizing anti-drug antibody (nAb)

Plasma samples will be collected to evaluate the incidence of ADA and nAb.
Timepoint [3] 411803 0
Anti-Drug Antibody (ADA) incidence will be measured at the following timepoints:

Day 1 Pre-dose, Day 15, Day 29, and Day 43 (End of Study) and Early Termination Visit.
Secondary outcome [4] 411804 0
To assess the immunogenicity of EQ102 after multiple ascending SC doses.
Composite Immunogenicity endpoints include:
• Incidence of EQ102 ADA (anti-drug antibody).
• Incidence of neutralizing anti-drug antibody (nAb)

Plasma samples will be collected to evaluate the incidence of ADA and nAb.
Timepoint [4] 411804 0
Anti-Drug Antibody (ADA) incidence will be measured at the following timepoints:

Day 1 Pre-dose, Day 15 Pre-dose, Day 22 Pre-dose, Day 36, Day 50 and Day 64 (End of Study) and Early Termination Visit.
Secondary outcome [5] 411805 0
To assess Pharmacodynamics (PD) marker changes after single ascending SC doses of EQ102.
Exploratory PD endpoints include (but are not limited to):
• Receptor occupancy (RO) assessment
• Immunophenotyping (IPT)
• Serum PD assessments
• Cytokine quantification
• Lymphocyte subsets
Timepoint [5] 411805 0
Serum PD samples will be collected as follows:

Day 1 Pre-dose, Day 2 24 hrs post-dose, Day 4, Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43 (End of Study) and Early Termination Visit.
Secondary outcome [6] 411806 0
To assess Pharmacodynamics (PD) marker changes after multiple ascending SC doses of EQ102.
Exploratory PD endpoints include (but are not limited to):
• Receptor occupancy (RO) assessment
• Immunophenotyping (IPT)
• Serum PD assessments
• Cytokine quantification
• Lymphocyte subsets
Timepoint [6] 411806 0
Serum PD samples will be collected as follows:

Day 1 Pre-dose, Day 2 24 hrs post-dose, Day 4 72 hrs post-dose, Day 8 Pre-dose, Day 15 Pre-dose, Day 22 Pre-dose, Day 23 24 hrs post-dose, Day 29, Day 36, Day 50, and Day 64 (End of Study) and Early Termination Visit.

Eligibility
Key inclusion criteria
1. Males and females 18 to 55 years of age inclusive.
2. Body mass index (BMI) 18.0 to 32.0 kg/m2, with a body weight greater than or equal to 50 kg.
3. Medically healthy without clinically significant abnormalities.
4. Have suitable venous access for blood sampling
5. Additional vaccine requirements as outlined in the 'Public notes' field below
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of chronic alcohol abuse or excessive alcohol intake within 12 weeks prior to screening.
2. History of substance abuse or drug addiction within 12 months prior to first study drug administration and positive drug test results.
3. History of relevant drug hypersensitivity.
4. Smoke more than 2 nicotine containing products or equivalent per week or who are not willing to abstain from smoking 7 days prior to admission and during the confinement period(s).
5. Use of systemic immunomodulatory or immunosuppressant treatments 1 month or 5 half-lives of the medication (whichever is longer) prior to screening. Topical or inhaled corticosteroids are acceptable.
6. Use of any prescription or over-the-counter medication (including herbal products) – exceptions include oral contraceptives, occasional use of ibuprofen, paracetamol, topical ointments, and vitamins or dietary supplements.
7. Receipt of any investigational drug within 1 month of screening.
8. Positive for HIV-1 or HIV-2, hepatitis B virus (HBV), or Hepatitis C virus (HCV)
9. Positive QuantiFERON TB Test.
10. Use of any live or live attenuated vaccinations within 30 days prior to the first study drug administration except for vaccines for influenza.
11. Donation or receipt of blood or blood products.
12. Regular, excessive consumption of caffeine-containing products.

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)
This is a double-blind study. Blinding of study drug/placebo assignment is critical to the integrity of this clinical trial. Those blinded to study drug assignment include the Sponsor, the PI, clinical study personnel participating in participants’ care or clinical evaluations, and the study participants. Blinded personnel must not make any effort to determine which study drug therapy is being administered.

Those unblinded to study drug assignment include the statisticians preparing the randomization and code break envelopes, pharmacy personnel dispensing the study drugs, the unblinded study monitor, the bioanalytical laboratory, and the unblinded pharmacokineticist performing interim PK analysis for the SRC.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants who meet the study eligibility criteria will be assigned a randomization number pre-dose on Day 1, which corresponds to a study treatment (EQ102 or placebo). The allocation to EQ102 or placebo will be performed using a block randomization algorithm and will be documented in the study randomization schedule.
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
This is a first in human study for EQ102. As such, no formal sample size calculations have been performed.

The sample size for this study of 6 EQ102 treated participants and 2 placebo participants in each dose cohort (total approximately 72 participants) for both SAD and MAD parts of the study is considered adequate to meet the objectives of the study.

A formal statistical analysis plan will be developed and finalized before database lock.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
30/09/2022
Date of last participant enrolment
Anticipated
Actual
15/08/2023
Date of last data collection
Anticipated
Actual
23/01/2024
Sample size
Target
72
Accrual to date
Final
56
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22795 0
Nucleus Network - Melbourne
Recruitment hospital [2] 22796 0
Nucleus Network - Geelong
Recruitment postcode(s) [1] 38081 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 311817 0
Commercial sector/Industry
Name [1] 311817 0
Equillium AUS PTY Ltd
Country [1] 311817 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Equillium AUS PTY Ltd
Address
Suite 5.02, Level 5 139 Macquarie Street Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 313888 0
None
Name [1] 313888 0
Address [1] 313888 0
Country [1] 313888 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311262 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 311262 0
Ethics committee country [1] 311262 0
Australia
Date submitted for ethics approval [1] 311262 0
03/08/2022
Approval date [1] 311262 0
01/09/2022
Ethics approval number [1] 311262 0

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

Contacts
Principal investigator
Name 120490 0
Dr Philip Ryan
Address 120490 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 120490 0
Australia
Phone 120490 0
+61 438 009 787
Fax 120490 0
Email 120490 0
[email protected]
Contact person for public queries
Name 120491 0
Philip Ryan
Address 120491 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 120491 0
Australia
Phone 120491 0
+61 438 009 787
Fax 120491 0
Email 120491 0
[email protected]
Contact person for scientific queries
Name 120492 0
Philip Ryan
Address 120492 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 120492 0
Australia
Phone 120492 0
+61 438 009 787
Fax 120492 0
Email 120492 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.