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Trial registered on ANZCTR


Registration number
ACTRN12624000238572p
Ethics application status
Submitted, not yet approved
Date submitted
30/01/2024
Date registered
11/03/2024
Date last updated
11/03/2024
Date data sharing statement initially provided
11/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A First-in-human Study of APG808 in Healthy Participants
Scientific title
A Phase 1, Randomized, Blinded, Placebo-controlled, Single Ascending Dose, First-in-human, Study of the Safety, Tolerability, and Pharmacokinetics of APG808 in Healthy Participants
Secondary ID [1] 311437 0
APG808-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic obstructive pulmonary disease 332531 0
Condition category
Condition code
Respiratory 329629 329629 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will evaluate single ascending doses (SAD) of APG808 administered subcutaneously (SC) in healthy participants. It will consist of a maximum of 4 cohorts and each cohort will consist of up to 8 healthy participants. Participants will be randomized 6:2 to APG808 or placebo (up to 32 participants total) in 1 of the 4 treatment cohorts.

Cohort 1 - APG808 Dose 150 milligram (mg) or placebo
Cohort 2 - APG808 Dose 300 mg or placebo
Cohort 3 - APG808 Dose 600 mg or placebo
Cohort 4 - APG808 Dose 1200 mg or placebo

The study will be conducted at only one site in Australia. The anticipated duration of the study is up to 210 days.
Intervention code [1] 327740 0
Treatment: Drugs
Comparator / control treatment
Placebo (0.9% sodium chloride) solution will be administered via SC injection.
Control group
Placebo

Outcomes
Primary outcome [1] 337162 0
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
Timepoint [1] 337162 0
Day 1: 0, 4, 8, 24, 48 and 72 hours post-dose and on Days 8, 11, 15, 22, 29, 57, 85, 113, 141 and 169 post-dose
Secondary outcome [1] 430504 0
Assessment of Pharmacokinetics (PK) Parameters: Cmax, tmax, terminal elimination rate constant (lambda z), t1/2, AUC, AUC0-last, AUC0-inf, CL/F, Vz/F
Timepoint [1] 430504 0
Day 1: pre-dose, 4, 8 and 24 hours post-dose and on Days 3, 4, 8, 11, 15, 22, 29, 57, 85, 113, 141 and 169 post-dose
Secondary outcome [2] 430505 0
Number of Participants With Anti-drug Antibodies (ADA)
Timepoint [2] 430505 0
Pre-dose on Day 1; and post-dose on Days 1, 15, 22, 29, 57, 85, 113, 141 and 169
Secondary outcome [3] 430967 0
Ratio of Cmax in Participants With or Without ADA
Timepoint [3] 430967 0
Day 1: pre-dose, 4, 8 and 24 hours post-dose and on Days 3, 4, 8, 11, 15, 22, 29, 57, 85, 113, 141 and 169 post-dose
Secondary outcome [4] 432051 0
Ratio of AUC in Participants With or Without ADA
Timepoint [4] 432051 0
Day 1: pre-dose, 4, 8 and 24 hours post-dose and on Days 3, 4, 8, 11, 15, 22, 29, 57, 85, 113, 141 and 169 post-dose

Eligibility
Key inclusion criteria
1. Healthy men and women, in the opinion of the Investigator and as determined by physical examination, laboratory screening tests, and medical history
2. 18 to 65 years of age (inclusive) with a body mass index of 18 to 35 kg/m^2 (kilogram per square meter) (inclusive), weight <120 kg
3. Willing and able to speak, read, and understand English, and provide written informed consent after the nature of the study has been explained and prior to the start of any study procedures
4. Willing and able to attend the necessary visits to the CRU, and comply with all testing and requirements defined in the protocol
5. Willing and able to remain at the study site unit for the duration of the confinement period and return for the outpatient visit(s) defined in the protocol
6. Willing to use a highly effective method of contraception from admission through 30 days after EOS (end of the study) or 5 half-lives after the last administration of study drug, whichever is longer
7. Willing to abstain from regular, continuous alcohol use (defined as an average of >10 standard drinks per week or at the Investigator's discretion) or tobacco use (defined as >=5 cigarettes per day or equivalent) for 48 hours prior to admission to the CRU (Day -1) and any illicit drug abuse for >=48 hours prior to admission to the CRU (Day -1)
8. Non-tattooed, clear injection site (i.e., absence of dermatologic conditions, such as scarring or rash, that may impact the ability to assess injection site reactions) suitable for SC injection and monitoring in the opinion of the Investigator
9. Agrees to comply with the drawing of blood samples for the PK and PD assessments
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Evidence of clinically significant abnormalities or disease
a. Diagnosis of diabetes mellitus
b. Positive test for human immunodeficiency virus antibody
c. Acute or chronic hepatitis B or C as evidenced by hepatitis B surface antigen and/or hepatitis C antibody; evidence of resolved infection or status post-vaccination with the presence of antibodies or documented absence of viral deoxyribonucleic acid on polymerase chain reaction is allowed
d. Diagnosis or suspected diagnosis of immunodeficiency or autoimmune diseases, or undergoing immunosuppressive therapy such as anticancer chemotherapy or radiotherapy before the trial, or has received systemic corticosteroid treatment (topical corticosteroids are acceptable) within the past 120 days before dosing
e. 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
f. History or presence of conditions which, in the judgment of the Investigator, are known to
interfere with the absorption, distribution, metabolism, or excretion of drugs
g. Liver function tests (i.e., alanine aminotransferase, aspartate aminotransferase) >1.5 times the upper limit of normal; elevated bilirubin is not allowed unless due to Gilbert's syndrome
h. Neutrophils >1.5 times the upper limit of normal
i. Impaired renal function defined as an estimated glomerular filtration rate <60 mL/min/1.73 m^2 (milliliter per minute per square meter) at Screening
j. Any other laboratory, vital sign (e.g., hypertension that could be unsafe for study drug administration per Investigator assessment), ECG abnormality (e.g., QTcF prolongation), clinically significant medical condition (e.g., cardiac failure), or finding that, in the Investigator's opinion, is likely to unfavorably alter the risk of study participation, confound study results, or interfere with the study conduct or compliance; participants may be rescreened and tests may be repeated at the Investigator's discretion. Note: participants with history of non-clinically significant disease (e.g., childhood asthma, migraines, non-hospitalized depression, Gilbert syndrome, cholecystectomy) that, in the Investigator's opinion, is not likely to unfavorably alter the risk of study participation, confound study results, or interfere with the study conduct or compliance may be eligible for the study
2. Poor peripheral venous access
3. Fever (>=38.0°C) within 7 days before study drug administration
4. Positive COVID-19 Rapid Antigen Test at admission to the CRU
5. Known history of illicit drug abuse, harmful alcohol use (defined as an average of > 10 standard drinks per week or at the Investigator’s discretion) or alcoholism, and/or heavy tobacco use (defined as >=5 cigarettes per day or equivalent) within 2 years prior to Screening (or at the Investigator’s discretion); positive screen for drugs of abuse (except tetrahydrocannabinol), or positive cotinine or alcohol breath test at Screening or admission to the CRU (or at the Investigator’s discretion), and participants must abstain from cigarette smoking for the duration of their stay in the CRU. Participants may be rescreened for drugs of abuse or alcohol breath test at the Investigator’s discretion
6. History of severe allergic reactions or hypersensitivity (i.e., anaphylaxis)
7. Known or suspected intolerance or hypersensitivity to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies or antibody fragments, or to any components of the formulation of APG808 and its excipients used in this study
8. If female, nursing, lactating, pregnant, or plans to become pregnant within 30 days of EOS or 5 half-lives (whichever is longer) of last study drug administration
9. Donation or loss of >=1 unit (450 mL) of whole blood within 1 month prior to dosing or plasma donations within 7 days of dosing
10. Use of any prescription or nonprescription medication 48 hours prior to dosing through CRU
discharge Day 4 (exception: contraceptives, hormone replacement therapy, vitamins, over-the counter (OTC) antihistamines, OTC topical steroids, or acetaminophen/paracetamol up to 2 g per day prior to dosing is permitted)
11. Vaccination within 14 days prior to administration of APG808
12. 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
13. Unable to comply with study requirements or in the opinion of the Investigator should not participate in this study

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)
Allocation is concealed and involves contacting the holder of the allocation schedule (randomization list), who is an off-site unblinded pharmacist.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table from a statistic book.
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
Not yet recruiting
Date of first participant enrolment
Anticipated
8/04/2024
Actual
Date of last participant enrolment
Anticipated
18/08/2024
Actual
Date of last data collection
Anticipated
1/02/2025
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 315545 0
Commercial sector/Industry
Name [1] 315545 0
Apogee Therapeutics, Inc.
Country [1] 315545 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Apogee Therapeutics, Inc.
Address
Inc. 221 Crescent St. Waltham, MA 02453
Country
United States of America
Secondary sponsor category [1] 317821 0
None
Name [1] 317821 0
Address [1] 317821 0
Country [1] 317821 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314444 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 314444 0
123 Glen Osmond Road, Eastwood SA 5063 (https://bellberry.com.au/)
Ethics committee country [1] 314444 0
Australia
Date submitted for ethics approval [1] 314444 0
17/01/2024
Approval date [1] 314444 0
Ethics approval number [1] 314444 0

Summary
Brief summary
The main aim of the study is to evaluate the safety and tolerability of single doses of APG808 in healthy participants.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131602 0
Dr Xiu Qin Lim
Address 131602 0
CMAX Clinical Research Pty. Ltd. Ground Floor, 21-24 North Terrace, Adelaide 5000, South Australia
Country 131602 0
Australia
Phone 131602 0
+61 423 224 361
Fax 131602 0
Email 131602 0
[email protected]
Contact person for public queries
Name 131603 0
Dr Kelly Harris
Address 131603 0
CMAX Clinical Research Pty. Ltd. Ground Floor, 21-24 North Terrace, Adelaide 5000, South Australia
Country 131603 0
Australia
Phone 131603 0
+61 8 7088 7900
Fax 131603 0
Email 131603 0
[email protected]
Contact person for scientific queries
Name 131604 0
Dr Xiu Qin Lim
Address 131604 0
CMAX Clinical Research Pty. Ltd. Ground Floor, 21-24 North Terrace, Adelaide 5000, South Australia
Country 131604 0
Australia
Phone 131604 0
+61 423 224 361
Fax 131604 0
Email 131604 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.