Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000086561
Ethics application status
Approved
Date submitted
22/12/2023
Date registered
31/01/2024
Date last updated
13/06/2024
Date data sharing statement initially provided
31/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Subcutaneous, Ascending Single and Multiple Doses of AP13 in Healthy Adults
Scientific title
A Randomised, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Subcutaneous, Ascending Single and Multiple Doses of AP13 in Healthy Adults
Secondary ID [1] 310995 0
AP13CP01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Hypertension 332098 0
Condition category
Condition code
Cardiovascular 328923 328923 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised, double-blind, placebo-controlled study of AP13 administered subcutaneously (SC) as single or multiple doses. The study will be conducted in 2 parts:

Part A Single ascending dose (SAD) will comprise of up to 5 cohorts. Each cohort will enrol 8 participants, with 6 randomised to receive a single dose of AP13 and 2 to receive placebo on Day 1 with a dose range of 0.3 - 12 mg/kg.

Part B Multiple ascending dose (MAD) will comprise of up to 3 cohorts. Each cohort will enrol 10 participants, with 8 randomised to receive one SC dose of AP13 and 2 to receive placebo every two weeks (Q2W) on Days 1, 15 and 29 (total of 3 doses) with a dose range of 3-12 mg/kg.

Part B may commence following review of available data from Day 15 of Part A SAD Cohort 3 by the Safety Review Committee.

Cohorts will be dosed in an escalating order with participants only able to enrol in one dose cohort.

Adherence to the intervention will be done via supervised drug administration.
Intervention code [1] 327441 0
Treatment: Drugs
Comparator / control treatment
The placebo used in this study will be normal sterile saline (0.9% sodium chloride).
Control group
Placebo

Outcomes
Primary outcome [1] 336631 0
To evaluate the safety and tolerability of AP13 (SAD)
Timepoint [1] 336631 0
Adverse events - will be graded using a three-point severity scale (mild, moderate, severe) and assessed continuously as they are reported or observed and reviewed daily from Screening until Day 96 post-dose (End of Study/Early Termination visit [EOS/ETV]).

Local tolerability will be graded based on the FDA Guidance for Industry document entitled Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (2007) with assessments to include measures of pain, tenderness, pruritus, erythema and induration measured within 0.5 hrs pre-dose Day 1 - 2, 4, 8, and 12 hours post-dose, Day 2 - Day 96 post-dose (EOS/ETV).

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer respiratory rate by manual breath count, temperature by thermometer and blood oxygen saturation by pulse oximeter. Measured at Screening, Day -1, pre-dose Day 1 - 1, 2, 4, 8, and 12 hrs post-dose, Day 2 - Day 96 post dose (EOS/ETV).

Electrocardiogram (ECG) - 12-lead ECG recordings will be obtained in triplicate at screening, pre-dose Day 1 2 hrs post-dose, Days 6, 8 and Day 10 post-dose. Single recordings will be obtained from Day -1, Day 2 post-dose, and Day 96 post-dose (EOS/ETV).

Clinical laboratory evaluations (haematology, serum chemistry, coagulation and urinalysis) - blood and urine samples will be collected from Screening, Day -1, Days 2, 3, 8, 15, 29, 43, 72 and Day 96 post dose (EOS/ETV).
Primary outcome [2] 336632 0
To evaluate the safety and tolerability of AP13 (MAD)
Timepoint [2] 336632 0
Adverse events - will be graded using a three-point severity scale (mild, moderate, severe) and assessed continuously as they are reported or observed and reviewed daily from Screening until Day 125 post-dose (End of Study/Early Termination visit [EOS/ETV]).

Local tolerability will be graded based on the FDA Guidance for Industry document entitled Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (2007) with assessments to include measures of pain, tenderness, pruritus, erythema and induration measured within 0.5 hrs pre-dose Day 1 - 2, 4, 8, and 12 hours post-dose, Day 2 - Day 14 post-dose, 0.5 hr pre-second dose Day 15 - 2, 4 hours post-second dose. Days 16, 22 and Day 28 post-second dose, 0.5 hr pre-third dose Day 29 - 2, 4 hours post-third dose, Day 30 - Day 125 post-dose (EOS/ETV).

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer respiratory rate by manual breath count, temperature by thermometer and blood oxygen saturation by pulse oximeter. Measured at Screening, Day -1, pre-dose Day 1 - 1, 2, 4, 8, and 12 hrs post-dose, Day 2 - Day 14 post-dose, pre-second dose Day 15 - 1, 2 and 4 hrs post-second dose, Day 16 - Day 28 post-second dose, pre-third dose Day 29 - 1, 2 and 4 hrs post-third dose, Day 30 - Day 125 post-dose (EOS/ETV).

Electrocardiogram (ECG) - 12-lead ECG recordings will be obtained in triplicate at screening, pre-dose Day 1 2 hrs post-dose, Day 15, 29 and Day 37 post-dose. Single recordings will be obtained from Day -1, Day 2 post-dose, and Day 125 post-dose (EOS/ETV).

Clinical laboratory evaluations (haematology, serum chemistry, coagulation and urinalysis) - blood and urine samples will be collected from Screening, Day -1, Days 2, 3, 8, 14, 28, 37, 57, 71, 101 and Day 125 post dose (EOS/ETV).
Secondary outcome [1] 429059 0
To evaluate the pharmacokinetic (PK) profile of AP13 (SAD)
Timepoint [1] 429059 0
Blood plasma will be collected 0.5 hr pre-dose Day 1 - 2, 4, 8, 12 hrs post-dose, Day 2 24hrs post-dose, Day 3 48 hrs post-dose, then Day 4 - Day 96 post dose (End of Study/Early Termination visit [EOS/ETV]).
Secondary outcome [2] 429060 0
To evaluate the pharmacokinetic (PK) profile of AP13 (MAD)
Timepoint [2] 429060 0
Blood plasma will be collected 0.5 hr pre-dose Day 1 - 2, 4, 8, 12 hrs post-dose, Day 2 24hrs post-dose, Day 3 48 hrs post-dose, Day 8 post-dose, 0.5 hr pre-second dose Day 15, 0.5 hr pre-third dose Day 29, then Day 35 - Day 125 post dose (End of Study/Early Termination visit [EOS/ETV]).
Secondary outcome [3] 429061 0
To evaluate the immunogenicity of AP13 (SAD)
Timepoint [3] 429061 0
Blood plasma will be collected 0.5 hr pre-dose Day 1, Days 29, 43, 72 and Day 96 post dose (End of Study/Early Termination visit [EOS/ETV]).
Secondary outcome [4] 429062 0
To evaluate the immunogenicity of AP13 (MAD)
Timepoint [4] 429062 0
Blood plasma will be collected 0.5 hr pre-dose Day 1, 0.5 hr pre-third dose Day 29, then Days 43, 71 and Day 125 post dose (End of Study/Early Termination visit [EOS/ETV]).

Eligibility
Key inclusion criteria
1. Healthy adult males and females, 18 to 55 years of age (inclusive) at screening.
2. Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 30.0 kg/m2, with a body weight 50 to 100 kg at screening.
3. Is medically healthy (in the opinion of the PI [or delegate]), as determined by pre-study medical history, and without clinically significant abnormalities including:
a. Physical examination without any clinically relevant findings.
b. Systolic blood pressure in the range of 90 to 140 mmHg and diastolic blood pressure in the range of 40 to 90 mmHg after 5 minutes in semi-supine position.
c. Heart rate in the range of 40 to 90 bpm after 5 minutes rest in semi-supine position.
d. Body temperature (tympanic), between 35.5°C and 37.7°C.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric or neurological disease/disorder within the past 3 months, or any acute minor illness (e.g. common cold, influenza, minor infection) within the past 1 month, determined by the PI (or delegate) to be clinically relevant.
2. History of surgery or hospitalisation within 3 months prior to screening, or surgery planned during the study.
3. Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
4. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
5. Positive test results for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
6. Positive drugs of abuse test or alcohol breath test results at the screening visit or on admission to the clinic on Day -1.
7. Females who are breastfeeding or planning to breastfeed during the study.
8. Use of any prescription or over-the-counter medication (including herbal products, diet aids, vitamins, and hormone supplements) within 7 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of study drug. Note: use of hormonal contraceptives and the occasional use of paracetamol (up to 2 grams per day) and ibuprofen (up to 1.2 grams per day) is permitted.
9. Donation of blood or plasma within 30 days prior to first dose of study drug, or loss of whole blood of more than 500 mL within 30 days prior to first dose of study drug, or receipt of a blood transfusion within 1 year of the first dose of study drug. Donating blood is permitted only 120 days (5 x AP13 t1/2) following the last dose of study drug.
10. Any other condition or prior therapy that in the opinion of the PI (or delegate) would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

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)
Participants who meet the study eligibility criteria will be assigned a randomisation number on Day -1 (or prior to dose administration on Day 1), which corresponds to a study treatment (AP13 or placebo). The randomisation schedule will be prepared prior to study start. Code-break tamper-evident envelopes containing treatment allocation per participant will be provided to the study site for emergency unblinding if required.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to AP13 or placebo for the non-sentinel participants will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule. Randomisation numbers assigned will be in accordance with this randomisation schedule.
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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This is the FIH study with AP13 and as such no formal sample size calculation was performed. The planned sample size of n=8 per cohort for SAD (1:3 placebo: active), and n=10 per cohort for MAD (1:4 placebo: active) is considered adequate for the study objectives.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/02/2024
Actual
27/02/2024
Date of last participant enrolment
Anticipated
15/10/2024
Actual
Date of last data collection
Anticipated
16/02/2025
Actual
Sample size
Target
70
Accrual to date
16
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 25877 0
Nucleus Network - Melbourne
Recruitment hospital [2] 25878 0
Nucleus Network - Geelong
Recruitment hospital [3] 25956 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 41710 0
3004 - Melbourne
Recruitment postcode(s) [2] 41791 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 315258 0
Commercial sector/Industry
Name [1] 315258 0
Apollo Therapeutics
Country [1] 315258 0
United Kingdom
Primary sponsor type
Commercial sector/Industry
Name
Apollo Therapeutics
Address
3rd Floor 22 Station Road Cambridge CB1 2JD United Kingdom
Country
United Kingdom
Secondary sponsor category [1] 317292 0
Commercial sector/Industry
Name [1] 317292 0
Avance Clinical Pty Ltd
Address [1] 317292 0
213 Glynburn Road, Firle, South Australia, 5070
Country [1] 317292 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314175 0
Alfred HREC
Ethics committee address [1] 314175 0
Ethics committee country [1] 314175 0
Australia
Date submitted for ethics approval [1] 314175 0
21/11/2023
Approval date [1] 314175 0
19/12/2023
Ethics approval number [1] 314175 0
HREC/104062/Alfred-2023 (Local Reference: Project 705/23)

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

Contacts
Principal investigator
Name 130682 0
Dr Gloria Wong
Address 130682 0
Q-Pharm Pty Ltd, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 130682 0
Australia
Phone 130682 0
+61 07 3707 2720
Fax 130682 0
Email 130682 0
[email protected]
Contact person for public queries
Name 130683 0
Gloria Wong
Address 130683 0
Q-Pharm Pty Ltd, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 130683 0
Australia
Phone 130683 0
+61 07 3707 2720
Fax 130683 0
Email 130683 0
[email protected]
Contact person for scientific queries
Name 130684 0
Gloria Wong
Address 130684 0
Q-Pharm Pty Ltd, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 130684 0
Australia
Phone 130684 0
+61 07 3707 2720
Fax 130684 0
Email 130684 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.