Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000786695
Ethics application status
Approved
Date submitted
22/06/2023
Date registered
19/07/2023
Date last updated
27/05/2024
Date data sharing statement initially provided
19/07/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A First-in-human Study of APG777 in Healthy Participants
Scientific title
A Phase 1, Randomized, Blinded, Placebo-Controlled, Single and Multiple Dose, First-in-human Study of the Safety, Tolerability, and Pharmacokinetics of APG777 in Healthy Participants
Secondary ID [1] 309850 0
APG777-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 330293 0
Condition category
Condition code
Skin 327150 327150 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
IP Name: APG777
Treatment: Drug – APG777
Treatment Drug – Placebo

Single ascending dose (SAD) Cohorts
1. Cohort 1: APG777 (Low dose) or Placebo - Participants will receive single subcutaneous (SC) injection of low dose (300 mg) of APG777 or placebo
2. Cohort 2: APG777 (Medium dose) or Placebo – Participants will receive single subcutaneous injection of medium dose (600 mg) of APG777 or placebo
3. Cohort 3: APG777 (High dose) or Placebo - Participants will receive single subcutaneous injection of high dose (1200 mg) of APG777 or placebo

Study drug will be administered as a subcutaneous (SC) injection by trained personnel at the clinical research unit (CRU) and administration will be noted in patient medical records.

Multiple dose (MD) Cohorts
1. Cohort 1: Participants will receive 300 mg of APG777 or placebo by subcutaneous injection on Day 1 and Day 29
2. Cohort 2: Participants will receive 300 mg of APG777 or placebo by subcutaneous injection on Day 1 and Day 15

Study drug will be administered as a SC injection by trained personnel at the CRU.

The first MD cohort will be enrolled after the SRC has reviewed a minimum of 14 days post dose (Day 15) of safety and PK data from the SAD cohort.
Approval of the MD part of the study is subject to HREC submission and approval.
Intervention code [1] 326285 0
Treatment: Drugs
Comparator / control treatment
Placebo is 0.9% Sodium Chloride Solution for Injection
Placebo will be used for SAD and MD cohorts.

Control group
Placebo

Outcomes
Primary outcome [1] 335027 0
SAD/MD Cohort: To evaluate the safety and tolerability of APG777
- Incidence of Treatment Emergent Adverse Events (TEAEs) coded based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
- Incidence of clinically significant laboratory findings (Chemistry using serum, Hematology. Urinalysis)
- Incidence of clinically significant vital signs include heart rate through stethoscope, blood pressure through digital Sphygmomanometer, body temperature, and respiratory rate
- Incidence of clinically significant changes in electrocardiograms
Timepoint [1] 335027 0
SAD Cohorts:
Day -1 (pre-treatment), and post initiation of treatment on Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253 and Day 337.

MD (Day 1 and Day 29 dosing):
Day -1 (pre-treatment), and post-initiation of treatment on Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 28. Post initiation of 2nd treatment on Day 29, Day 30, Day 36, Day 43, Day 50, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253 and Day 337.

MD (Day 1 and Day 15 dosing): Day -1 (pre-treatment), and post-initiation of treatment on Day 1, Day 2, Day 3, Day 4, Day 8, Day 14. Post initiation of 2nd treatment on Day 15, Day 16, Day 22, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253 and Day 337.
Secondary outcome [1] 422752 0
SAD/MD Cohort: To characterize the single dose and multi-dose PK of APG777
Blood samples will be collected from all participants.
Parameters:
- Maximum observed concentration (Cmax)
- Time to reach Cmax (Tmax)
- Apparent first-order terminal elimination rate constant
- Apparent first-order terminal elimination half-life
- The area under the concentration-time curve from time 0 to the last observed non-zero concentration
- The area under the concentration-time curve from time 0 extrapolated to infinity.
- Apparent total clearance after administration
- Apparent volume of distribution during the terminal elimination phase after administration
Timepoint [1] 422752 0
SAD Cohorts
Day 1 (less than 1hr prior to dose), and post-dose on Day 1 (4 h ± 30 min, 8 h ± 1 h), Day 2 (24 h ± 2 h), Day 3 (48 h ± 2 h), Day 4 (72 h ± 4 h) and on Day 8, Day 15, Day 22, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337.

MD (Day 1 and Day 29 dosing)
Day 1 (less than 1hr prior to dose), and post-dose on Day 1 (4 h ± 30 min, 8 h ± 1 h), Day 2 (24 h ± 2 h), Day 3 (48 h ± 2 h), and on Day 8, Day 15, and Day 22.
Day 29 (less than 1hr prior to dose), and post-dose on Day 29 (4 h ± 30 min, 8 h ± 1 h), Day 30 (24 h ± 2 h), Day 36, Day 43, Day 50, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337.

MD (Day 1 and Day 15 dosing)
Day 1 (less than 1hr prior to dose), and post-dose on Day 1 (4 h ± 30 min, 8 h ± 1 h), Day 2 (24 h ± 2 h), Day 3 (48 h ± 2 h), Day 4 (72 h ± 2 h), Day 8, and Day 14.
Day 15 (less than 1hr prior to dose), and post-dose on Day 15 (4 h ± 30 min, 8 h ± 1 h), Day 16 (24 h ± 2 h), Day 22, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337.
Secondary outcome [2] 422753 0
SAD/MD Cohort: Number of participants with antibodies to APG777
Serum samples will be collected for analysis of immunogenic response to determine presence/absence and titers of anti-drug antibodies
Timepoint [2] 422753 0
SAD Cohorts
Post-dose on Day 1 (0h), Day 15, Day 22, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, Day 337.

MD (Day 1 and Day 29 dosing)
Post-dose on Day 1 (0h), Day 15, and Day 22.
Post-dose on Day 29 (0h), Day 43, Day 50, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337.

MD (Day 1 and Day 15 dosing)
Post-dose on Day 1 (0h).
Post-dose on Day 15 (0h), Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337.

Eligibility
Key inclusion criteria
• Healthy men and women, as determined by physical examination, laboratory screening tests, and medical history
• Body mass index (BMI) of 18 to 35 kg/m2 (inclusive), weight less than 120 kg
• Willing to use a highly effective method of contraception from admission through 12 months or 5 half-lives, whichever is longer, after the last administration of study drug
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Evidence of clinically significant abnormalities or disease, including, but not limited to,
a) Hemoglobin A1c more than or equal to 6.5% and/or diagnosis of diabetes mellitus;
b) Positive test for human immunodeficiency virus (HIV) antibody;
c) Acute or chronic hepatitis B or C;
d) Diagnosis or suspected diagnosis of immunodeficiency or autoimmune diseases, or undergoing immunosuppressive therapy; d) Significant history or clinical manifestation of any metabolic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, acute or chronic infectious diseases and malignancies, as determined by the Investigator
• History of severe allergic reactions or hypersensitivity (ie, anaphylaxis)
• Known or suspected intolerance or hypersensitivity to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, mAbs or antibody fragments, or to any components of the formulation of APG777 and its excipients used in this study
• If female, nursing, lactating, pregnant. or plans to become pregnant within 12 months or 5 half-lives (whichever is longer) of last study drug administration
• Use of any prescription or non-prescription medication 48 hours prior to dosing (exception: contraceptives or acetaminophen/paracetamol up to 2 g per day prior to dosing is permitted).
• Vaccination within 14 days prior to administration of APG777
• Use of any investigational drug therapy within 30 days or 5 half-lives (whichever is longer) prior to study drug dosing through 5 half-lives after the last dose of study drug

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)
The allocation procedures is per centralised randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
27/07/2023
Actual
31/07/2023
Date of last participant enrolment
Anticipated
31/03/2024
Actual
23/02/2024
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 24888 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 40538 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 314035 0
Commercial sector/Industry
Name [1] 314035 0
Apogee Therapeutics, Inc
Country [1] 314035 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Apogee Therapeutics, Inc
Address
221 Crescent St. Waltham, MA 02453
Country
United States of America
Secondary sponsor category [1] 315929 0
None
Name [1] 315929 0
Address [1] 315929 0
Country [1] 315929 0
Other collaborator category [1] 282697 0
Commercial sector/Industry
Name [1] 282697 0
Novotech (Australia) Pty Limited
Address [1] 282697 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 282697 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313169 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 313169 0
Ethics committee country [1] 313169 0
Australia
Date submitted for ethics approval [1] 313169 0
24/05/2023
Approval date [1] 313169 0
12/07/2023
Ethics approval number [1] 313169 0

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

Contacts
Principal investigator
Name 127234 0
Dr Xiu Qin Lim
Address 127234 0
CMAX Clinical Research Pty Ltd
Ground Floor, 21-24 North Terrace Adelaide 5000
South Australia
Country 127234 0
Australia
Phone 127234 0
+61 8 73214114
Fax 127234 0
Email 127234 0
[email protected]
Contact person for public queries
Name 127235 0
Kelly Harris
Address 127235 0
CMAX Clinical Research Pty Ltd
Ground Floor, 21-24 North Terrace Adelaide 5000
South Australia
Country 127235 0
Australia
Phone 127235 0
+61 8 7088 7999
Fax 127235 0
Email 127235 0
[email protected]
Contact person for scientific queries
Name 127236 0
Xiu Qin Lim
Address 127236 0
CMAX Clinical Research Pty Ltd
Ground Floor, 21-24 North Terrace Adelaide 5000
South Australia
Country 127236 0
Australia
Phone 127236 0
+61 8 73214114
Fax 127236 0
Email 127236 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

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

Documents added automatically
No additional documents have been identified.