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Trial registered on ANZCTR


Registration number
ACTRN12623000204640
Ethics application status
Approved
Date submitted
7/02/2023
Date registered
27/02/2023
Date last updated
3/04/2024
Date data sharing statement initially provided
27/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ALG-801 in Healthy Postmenopausal Women
Scientific title
A Phase Ib Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALG-801 in Postmenopausal Women
Secondary ID [1] 308897 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bone loss 328891 0
Muscle wasting 328892 0
Condition category
Condition code
Musculoskeletal 325888 325888 0 0
Normal musculoskeletal and cartilage development and function
Musculoskeletal 326053 326053 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
4 subcutaneous doses of ALG-801 given weekly over a period of one month.
3 ascending dose levels at 1 mg/kg, 3 mg/kg and 4.5 mg/kg will be tested.
Intervention code [1] 325343 0
Treatment: Drugs
Comparator / control treatment
4 subcutaneous doses of placebo (20 mM sodium phosphate buffer, 9% sucrose, and 0.01% polysorbate 20) given weekly over a period of one month.
Control group
Placebo

Outcomes
Primary outcome [1] 333722 0
Safety and tolerability of ALG-801 based on adverse event reports and the results of vital sign measurements (blood pressure using sphygmomanometer, pulse rate, and respiratory rate), ECGs, physical examinations, and clinical laboratory tests.

Possible side effects include skin rashes and injection site bruising and will be assessed by examinations of the injection site after dosing.
Timepoint [1] 333722 0
Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 50 post commencement of intervention.
Secondary outcome [1] 418070 0
Concentrations of ALG-801 during weekly administration of subcutaneous doses of ALG-801 at multiple doses will be measured using validated bioanalytical methods.

Serum will be tested. The pharmacokinetic parameters will include, but not be limited to, Tmax, Cmax, AUC0-t, AUC0-8, T1/2, CL/F and Vz/F.
Timepoint [1] 418070 0
PK assessments will be performed pre-dose and at 8- and 24-hours post-dose on Day 1, and on Days 3, 5, 8 (pre-dose), 15 (pre-dose), 22 (pre-dose), 29, 36, 43, and 50.
Secondary outcome [2] 418071 0
Immunogenicity of ALG-801 will be assessed in serum samples using an anti-drug antibody (ADA) assay.
Timepoint [2] 418071 0
Day 1, 22, and 50 post commencement of intervention.
Secondary outcome [3] 418940 0
Exploratory outcomes include changes in bone turnover markers BSAP, P1NP, and CTx in serum using validated analytical methods.
Timepoint [3] 418940 0
Day 1 (pre-dose), 15, 29 and 43 post commencement of intervention.
Secondary outcome [4] 418941 0
Exploratory outcomes include changes in thigh muscle volume from baseline using MRI.
Timepoint [4] 418941 0
Baseline, Day 29, and Day 43

Eligibility
Key inclusion criteria
-Subject is postmenopausal
-Body mass index (BMI) between 18.5 and 35 kg/m2 (inclusive)
-Free from clinically significant unstable medical problems as determined by the Investigator, and if medicated, the medication does not interfere with the investigational product
Minimum age
45 Years
Maximum age
75 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
-Hospitalization within the 3 months prior to the first dose of study treatment
-Has an established diagnosis of diabetes mellitus, as indicated by use of diabetes medication, Hb A1C greater than 6.4% or fasting glucose equal to 126 mg/dL (7.0 mmol/L)
-Positive test for drugs of abuse (including recreational drugs) at screening and admission to the research unit
-Receipt of an investigational study to evaluate pharmaceuticals or biologics within the past 1 month or 5 half-lives, whichever is longer
-Prior treatment with any ActRIIA- or ActRIIB-related ligand trap, such as KER-12, KER-50, ACE-536 (Luspatercept), ACE-011 (Sotatercept) and ACE-031
-History of any malignant cancer during the past 5 years, except treated nonmelanotic skin cancer or carcinoma in situ of the uterine cervix
-History of a major adverse cardiovascular event during the past 6 month
-History of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, autoimmune diseases, dermatologic, neurologic, oncologic, psychiatric disease (except for mild depression and anxiety)
-History of opportunistic infection within 6 months prior to screening or serious local infection or systemic infection within 3 months prior to screening
-Major surgery within 12 weeks prior to Day 1, except for minor cosmetic or dental procedures.
-Fever or symptomatic infection (viral or bacterial) within 7 days prior to Day 1
-Blood donation or significant blood loss (480mL or more) within 30 days prior to Day 1
-Hormone replacement therapy within 12 weeks prior to Day 1; infrequent use of estrogen vaginal creams (less than 3 times per week) is allowed
-Anti-osteoporosis medications (e.g., bisphosphonates, denosumab, teriparatide, romosozumab, etc.) within 28 days of first dosing or within 5 times the elimination half-life of the medication prior to first dosing, whichever is longer
-Systemic glucocorticoid therapy within 6 months prior to Day 1
-Protein supplements or nutritional supplements for muscle building or supplements which contain anabolic or ergogenic substances (e.g., creatine) within 28 days of first dosing
-History of significant bleeding disorder or known disease involving platelet number and/or function

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 by central randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Blocked, fixed randomisation method.
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
The sample size in each of the three cohorts consists of 10-11 subjects per dose group (8 active, 2-3 placebo) for exploratory evaluation of safety, tolerability, PK, and PD of ALG-801. The sample size in Cohort 1, Cohort 2, and Cohort 3 was not powered for any statistical hypothesis test.

All safety data will be tabulated with descriptive statistics. Data from all placebo subjects will be pooled. Data from ALG-801 treated subjects will be presented by dose (8 subjects per dose).

Pharmacokinetic data will be derived using all subjects who have sufficient plasma samples to allow for calculation of pharmacokinetic parameters. Pharmacokinetic parameters will include, but not be limited to, Tmax, Cmax, AUC0-t, AUC0-8, T1/2, CL/F and Vz/F. PK parameters will be summarized by dose group using descriptive statistics. Selected PK parameters will be analyzed by comparative statistics. Dose proportionality of PK parameters will be assessed by linear regression analysis.

Immunogenicity of ALG-801 will be assessed using an ADA assay pre-dose and on Days 22 and 50 to evaluate generation of ADA titers and any change in ADA titers over time.

PD assessments will be summarized using descriptive statistics for each dose group with respect to dose level and time point. PD effects will also be evaluated in relationship to systemic exposure.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/03/2023
Actual
13/04/2023
Date of last participant enrolment
Anticipated
30/11/2023
Actual
28/12/2023
Date of last data collection
Anticipated
Actual
28/12/2023
Sample size
Target
32
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 23906 0
Nucleus Network Brisbane Clinic - Herston
Recruitment postcode(s) [1] 39391 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 313108 0
Commercial sector/Industry
Name [1] 313108 0
AliveGen USA, Inc.
Country [1] 313108 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
AliveGen USA, Inc.
Address
810 Lawrence Drive, Suite 120
Thousand Oaks, California, 91320
Country
United States of America
Secondary sponsor category [1] 314807 0
Commercial sector/Industry
Name [1] 314807 0
Novotech (Australia) Pty Ltd
Address [1] 314807 0
Level 3, 235 Pyrmont Street
Pyrmont, NSW 2009
Australia
Country [1] 314807 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312357 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 312357 0
Ethics committee country [1] 312357 0
Australia
Date submitted for ethics approval [1] 312357 0
01/02/2023
Approval date [1] 312357 0
10/03/2023
Ethics approval number [1] 312357 0

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

Contacts
Principal investigator
Name 124366 0
Dr Richard Friend
Address 124366 0
Nucleus Network, Level 5, 300C Herston Rd, Herston, QLD 4006
Country 124366 0
Australia
Phone 124366 0
+61 403 415 925
Fax 124366 0
Email 124366 0
r.Friend@nucleusnetwork.com.au
Contact person for public queries
Name 124367 0
David Browning
Address 124367 0
AliveGen USA, Inc.
801 Lawrence Drive, Suite 102
Thousand Oaks, California 91320
Country 124367 0
United States of America
Phone 124367 0
+1 615 975 7776
Fax 124367 0
Email 124367 0
davidbrowning@alivegen.com
Contact person for scientific queries
Name 124368 0
David Browning
Address 124368 0
AliveGen USA, Inc.
801 Lawrence Drive, Suite 102
Thousand Oaks, California 91320
Country 124368 0
United States of America
Phone 124368 0
+1 615 975 7776
Fax 124368 0
Email 124368 0
davidbrowning@alivegen.com

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.