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Trial registered on ANZCTR


Registration number
ACTRN12625000800426p
Ethics application status
Submitted, not yet approved
Date submitted
7/07/2025
Date registered
28/07/2025
Date last updated
28/07/2025
Date data sharing statement initially provided
28/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Study on RUNX1 mRNA for Safety in Osteoarthritis Patients scheduled for Knee Replacement Surgery
Scientific title
A Phase 1, randomized, placebo controlled, first-in-human single ascending dose study of RUNX1 mRNA in primary osteoarthritis patients scheduled for total knee replacement
Secondary ID [1] 314702 0
Protocol Number: RUNX1 mRNA-001
Universal Trial Number (UTN)
U1111-1324-3463
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
osteoarthritis 337889 0
knee replacement 337890 0
Condition category
Condition code
Musculoskeletal 334220 334220 0 0
Osteoarthritis
Surgery 334514 334514 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a first-in-human (FIH), Phase 1, randomized, single-blind, placebo controlled study that is designed to investigate the safety and tolerability of single ascending doses of RUNX1 mRNA administered by intra-articular injection in participants with primary osteoarthritis (OA) who are scheduled to undergo knee replacement surgery. The study will evaluate up to 3 single ascending dose (SAD) cohorts (1 cohort per dose level). Four participants will be enrolled into each cohort and randomly assigned to receive either placebo (n=1) or RUNX1 mRNA (n=3) in a single blinded manner. Only the participant and pathologist will be blinded to study treatment.

Participants will receive a single dose of RUNX1 mRNA or placebo per their assigned treatment, which will be scheduled to occur on Day 1 followed by the planned knee replacement surgery on Day 5. The orthopaedic surgeon will administer the injection on Day 1. Following administration of RUNX1 mRNA or placebo, all participants will remain confined at the site for at least 2 hours post-dose and will undergo safety assessments per during this time. In the absence of clinically significant safety signals, and at the PI’s discretion, participants will be discharged from the site on the same day (Day 1) following completion of all protocol specified assessments.

A staggered dosing schedule will be used for dosing each cohort. The first 2 participants enrolled into a cohort will be randomized (in a 1:1 ratio to RUNX1 mRNA or placebo) and will be dosed ahead of the remaining participants in the cohort. If no acute, relevant safety issues are detected in the first 2 participants up to Day 5 (prior to the day of scheduled knee replacement surgery), the remaining participants in the cohort will be dosed. Dose level cohorts will be dosed sequentially, in an ascending dose fashion and dependent on clearance from the study Safety Monitoring Committee (SMC).

The planned starting dose of RUNX1 mRNA is 10 µg administered intra-articularly to the study knee. The anticipated dose range of RUNX1 mRNA for investigation in this study is 10, 20 and 40 µg administered to the study knee. Dose progression will confirmed based on emerging safety and tolerability data and is subject to review and clearance by the SMC.

The RUNX1 mRNA drug substance (DS) is a solution of the mRNA, which is a modified single-stranded mRNA consisting of 1,669 nucleotideresidues, with codon conversion and substitution of all uridines with N1-methylpseudouridine. It includes a5' cap and a poly(A) tail and encodes the full-length human transcription factor RUNX1.

RUNX1 mRNA DS is clear and colorless solution (1 mg/mL RUNX1 mRNA in 1 mmol/L sodium citrate, pH6.4), manufactured under current Good Manufacturing practice (cGMP) by TriLink BioTechnologies, LLC, aGMP licensed facility.
Intervention code [1] 331310 0
Treatment: Drugs
Comparator / control treatment
This study will evaluate up to 3 SAD (single ascending dose) cohorts (1 cohort per dose level). Four participants will be enrolled into each cohort and randomly assigned to receive either placebo (n=1) or RUNX1 mRNA (n=3), in a single-blind manner. Placebo for intra-articular administration into the study knee joint cavity will be sterile 5% glucose injection solution, administered in a total volume and appearance matched to the IP.
The injection procedure, including the technique and study knee location (joint), will be identical to that used for the administration of the active drug.
Control group
Placebo

Outcomes
Primary outcome [1] 341886 0
Laboratory safety data (clinical chemistry, hematology, coagulation, and urinalysis parameters). Safety laboratory data will be listed for each participant and summarized by treatment and protocol specified collection time point. This will be assessed as a composite outcome.
Timepoint [1] 341886 0
Screening visit (Day -28 to Day -1), Day 1, Day 5, Day of Discharge from Hospital (anticipated on Day 8 + 1 day), Follow-Up Day 19/End of Study.
Primary outcome [2] 341887 0
Vital signs. Vital signs will be listed for each participant and summarized by treatment and protocol specified collection time point. This will be assessed as a composite outcome.
Timepoint [2] 341887 0
Screening visit (Day -28 to Day -1), Day 1, Day 5 - pre and post surgery, Day of Discharge from Hospital (anticipated on Day 8 + 1 day), Follow-Up Day 19/End of Study.
Primary outcome [3] 341888 0
Electrocardiogram (ECG) monitoring
Timepoint [3] 341888 0
Screening visit (Day -28 to Day -1), Day 1, Day 5 - pre and post surgery, Day of Discharge from Hospital (anticipated on Day 8 + 1 day), Follow-Up Day 19/End of Study.
Secondary outcome [1] 448896 0
The pharmacodynamics (PD) of RUNX1 mRNA based on biomarkers of target engagement, biological activity, and mechanism of action by assessing protein levels.
Timepoint [1] 448896 0
Collection of specimens of removed knee material for PD analyses will occur following knee surgery on Day 5. The knee specimens will be transferred to the laboratory for analysis.
Secondary outcome [2] 449914 0
The pharmacodynamics (PD) of RUNX1 mRNA based on biomarkers of target engagement, biological activity, and mechanism of action by assessing mRNA levels.
Timepoint [2] 449914 0
Collection of specimens of removed knee material for PD analyses will occur following knee surgery on Day 5. The knee specimens will be transferred to the laboratory for analysis.

Eligibility
Key inclusion criteria
Age 18-85 years.
BMI between 18 and 40 kg/m².
Diagnosed with knee osteoarthritis per American College of Rheumatology (ACR) criteria.
Kellgren-Laurence grade 3-4 based on recent X-ray.
Scheduled for total knee replacement surgery.
Normal organ function with specific clinical parameters.
Stable medication use for knee osteoarthritis.
Females must be non-pregnant, non-lactating, and use effective contraception or be post-menopausal.
Females of childbearing potential must abstain from egg donation.
Males must be surgically sterile, abstinent, or use effective contraception.
Males must refrain from sperm donation.
Willingness to comply with protocol procedures and restrictions.
Ability to provide written informed consent.

Note: Participant suitability for knee replacement surgery will be assessed separately by the treating physician prior to screening. Requirements for the scheduled knee replacement surgery are additional to the eligibility criteria stipulated for RUNX1 mRNA-001 study participation.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe knee malalignment (varus/valgus > 20°).
Recent or planned arthroscopic examination of the target knee.
Recent or planned surgical treatment of the target knee (excluding total knee arthroplasty).
Inflammatory arthropathy, active infection, or systemic cartilage disorder.
Poorly controlled systemic disease.
Severe fluid collection in the target knee.
Recent corticosteroid use (excluding topical/nasal).
History of malignancy within the last 5 years (excluding certain skin cancers).
Clinically significant ECG findings.
History of anaphylaxis or severe allergies.
Positive pregnancy test, breastfeeding, or planning to breastfeed.
Clinically significant physical or laboratory findings.
History of significant disease that could interfere with study results.
Chronic liver disease or active infection (HIV, HBV, HCV).
Allergy or hypersensitivity to study components.
Active infection within 28 days prior to dosing.
Positive for Hepatitis B, Hepatitis C, or HIV.
Regular alcohol consumption exceeding weekly limits.
Positive urine drug test.

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 not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
There are no formal calculations of sample size for this study. The sample size has been chosen based on feasibility, to allow preliminary characterization of safety and tolerability exploratory PD of single ascending doses of RUNX1 mRNA.

The following analysis sets are defined for the study:
Safety set: will include all participants who receive at least 1 dose of study treatment (RUNX1 mRNA or placebo). The safety set will be used for the summaries of all safety data. Participants will be analyzed according to the actual study treatment received even if that differs from their randomized treatment.
PD set: will include all randomized participants who receive at least 1 dose of study treatment (RUNX1 mRNA or placebo) and who have at least one post-dose evaluable PD measurement of any parameter. Participants with dosing deviations that could potentially affect the PD profile will be excluded from the PD set at the discretion of the study team. The PD set will be used for the summaries of all PD data. Participants will be analyzed according to the actual study treatment received even if that differs from their randomized treatment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2025
Actual
Date of last participant enrolment
Anticipated
30/01/2026
Actual
Date of last data collection
Anticipated
20/03/2026
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 28124 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 44329 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 319252 0
Commercial sector/Industry
Name [1] 319252 0
PrimRNA AU Pty Ltd
Country [1] 319252 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
PrimRNA AU Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 321730 0
None
Name [1] 321730 0
None
Address [1] 321730 0
Country [1] 321730 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 317833 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 317833 0
Ethics committee country [1] 317833 0
Australia
Date submitted for ethics approval [1] 317833 0
07/07/2025
Approval date [1] 317833 0
Ethics approval number [1] 317833 0

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

Contacts
Principal investigator
Name 142298 0
A/Prof Booplan Ramasamy
Address 142298 0
The Royal Adelaide Hospital, 1 Port Rd Adelaide SA 5000
Country 142298 0
Australia
Phone 142298 0
+61 8 7074 2001
Fax 142298 0
Email 142298 0
[email protected]
Contact person for public queries
Name 142299 0
Booplan Ramasamy
Address 142299 0
The Royal Adelaide Hospital, 1 Port Rd Adelaide SA 5000
Country 142299 0
Australia
Phone 142299 0
+61 8 7074 2001
Fax 142299 0
Email 142299 0
[email protected]
Contact person for scientific queries
Name 142300 0
Amy Choi
Address 142300 0
PrimRNA AU Pty Ltd, Suite 1, Level 3, 62 Lygon Street, Carlton South, VIC 3053
Country 142300 0
Australia
Phone 142300 0
+61 3 8689 9997
Fax 142300 0
Email 142300 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.