Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000238572
Ethics application status
Approved
Date submitted
30/01/2024
Date registered
11/03/2024
Date last updated
3/10/2024
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 and in Patients With Mild-to-moderate Asthma
Scientific title
A Phase 1, Randomized, Blinded, Placebo-controlled, First-in-human Study of the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of APG808 in Healthy Participants and Multiple Doses in Patients With Mild-to-moderate Asthma
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
Asthma 335370 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 and multiple doses (MD) in patients with mild-to-moderate asthma. The SAD portion will consist of a maximum of 4 cohorts and each cohort will consist of up to 8 healthy participants. In the SAD portion, 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

For the MD cohort, dosing is planned on Days 1 and 29. In the MD cohort, approximately 20 patients will be randomized 3:1 to APG808 (300 mg per dose) or placebo.

The study will be conducted at multiple sites in Australia. The anticipated study duration for any individual participant in the SAD portion is up to approximately 210 days, including screening. The anticipated study duration for any individual patient in the MD cohort is up to approximately 238 days, including screening.
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
SAD and MD cohorts- 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
SAD cohorts- 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; MD cohort- Days 1 and 29: 0, 4, 8, 24, 48, and 72 hours post-dose and on Days 8, 15, 22, 36, 43, 50, 57, 85, 113, 141, 169, and 197 post-dose
Secondary outcome [1] 430504 0
Assessment of pharmacokinetics (PK) parameters for SAD cohorts and the MD cohort: Cmax, tmax, terminal elimination rate constant (lambda z), t1/2, AUC, AUC0-last, AUC0-inf, CL/F, Vz/F, AUC0-672
Timepoint [1] 430504 0
SAD cohorts- 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; MD cohort- Days 1 and 29: 0, 4, 8, 24, 48, and 72 hours post-dose and on Days 8, 15, 22, 36, 43, 50, 57, 85, 113, 141, 169, and 197 post-dose
Secondary outcome [2] 430505 0
SAD and MD cohorts- Number of healthy participants and number of patients with mild-to-moderate asthma with anti-drug antibodies (ADA)
Timepoint [2] 430505 0
SAD cohorts- Pre-dose on Day 1 and post-dose on Days 1, 15, 22, 29, 57, 85, 113, 141, and 169; MD cohort- Days 1 and 29: pre-dose, 4, 8, 24, 48, and 72 hours post-dose and post-dose on Days 8, 15, 22, 36, 43, 50, 57, 85, 113, 141, 169, and 197
Secondary outcome [3] 430967 0
SAD and MD cohorts- Ratio of Cmax and Ratio of AUC in both healthy participants and in patients with mild-to-moderate asthma with or without ADA
Timepoint [3] 430967 0
SAD cohorts- Day 1: pre-dose, 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; MD cohort- Days 1 and 29: pre-dose, 4, 8, 24, 48, and 72 hours post-dose and on Days 8, 15, 22, 36, 43, 50, 57, 85, 113, 141, 169, and 197 post-dose

Eligibility
Key inclusion criteria
For SAD cohorts-
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 with a body mass index of 18 to 35 kg/m^2 (kilogram per square meter), and weight <120 kg
3. 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
4. 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)

For MD cohort-
1. 18 to 65 years of age with a body mass index of 18 to 35 kg/m^2 and weight <120 kg
2. Physician diagnosis of mild or moderate asthma (as defined by Global Initiative for Asthma [GINA 2023]) >=1 year prior to Screening, and as determined by the Investigator through patient interview and/or review of medical history
3. Fractioned exhaled nitric oxide (FeNO) of >=25 parts per billion (ppb) at screening
4. A screening pre-bronchodilator FEV1 >=60% of predicted normal value
5. Asthma Control Test (ACT) score >19
6. Maintained control on as-needed short-acting beta-agonist (SABA) +/- stable dose of inhaled corticosteroids (ICS) or stable dose of ICS/LABA (long-acting beta-agonist), within permitted ICS dose as specified below; +/- stable dose of leukotriene receptor antagonist (LTRA). ICS dose should be stable for >=12 weeks prior to Day 1 and maintained during the course of the study, LTRA dose should be stable for >=8 weeks prior to Day 1 and maintained during the course of the study
7. Otherwise healthy other than asthma as defined above; patients with other mild, well controlled atopic diseases including allergic rhinitis and AD are permitted, provided no systemic therapies or intranasal or ocular corticosteroids are being used during screening or during the course of the study, and other inclusion/exclusion criteria are met
8. Willing to use a highly effective method of contraception from admission through 30 days after EOS or 5 half-lives after the last administration of study drug, whichever is longer
9. 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 drugs of abuse for >=48 hours prior to admission to the CRU (Day -1)
Note: Other protocol-defined inclusion criteria may apply.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
For SAD cohorts-
1. Evidence of clinically significant abnormalities or disease
2. 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 excessive 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
3. History of severe allergic reactions or hypersensitivity (i.e., anaphylaxis)
4. 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
5. 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

For MD cohort-
1. Any asthma exacerbation requiring systemic corticosteroids within 12 weeks of screening; any asthma exacerbation that resulted in overnight hospitalization within 6 months prior to screening
2. Any history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia
3. History of biologics use for treatment or control of asthma
4. Any concomitant respiratory disease that in the opinion of the Investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of patient safety or study results
5. Respiratory Infection
6. Evidence of clinically significant abnormalities or disease other than as previously described
7. Current smokers or patients with a smoking history of >=10 pack years (number of pack years = number of cigarettes per day/20*number of years smoked). Former smokers with <10 pack years must have stopped for at least 12 months to be eligible for screening
8. 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; 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). Patients may be rescreened for drugs of abuse or alcohol breath test at the Investigator’s discretion
9. History of severe allergic reactions or hypersensitivity (ie, anaphylaxis)
10. 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
11. 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
Note: Other protocol-defined exclusion criteria may apply.

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
Recruiting
Date of first participant enrolment
Anticipated
19/03/2024
Actual
19/03/2024
Date of last participant enrolment
Anticipated
31/01/2025
Actual
Date of last data collection
Anticipated
1/02/2025
Actual
Sample size
Target
52
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC

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
Approved
Ethics committee name [1] 314444 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 314444 0
Ethics committee country [1] 314444 0
Australia
Date submitted for ethics approval [1] 314444 0
17/01/2024
Approval date [1] 314444 0
14/02/2024
Ethics approval number [1] 314444 0
2023-02-179

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

Contacts
Principal investigator
Name 131602 0
Dr Emir Redzepagic
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 0413 231 264
Fax 131602 0
Email 131602 0
[email protected]
Contact person for public queries
Name 131603 0
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
Emir Redzepagic
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 0413 231 264
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.