Study on RUNX1 mRNA for Safety in Osteoarthritis Patients scheduled for Knee Replacement Surgery
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
PrimRNA AU Pty Ltd
12 participants
Oct 22, 2025
Interventional
Conditions
Summary
This study is a first-in-human, Phase 1 trial designed to test the safety and tolerability of RUNX1 mRNA in patients with primary osteoarthritis who are scheduled for knee replacement surgery. Participants will receive a single dose of RUNX1 mRNA or a placebo via intra-articular injection. The study will include up to three dose levels, with four participants in each group. The effects of RUNX1 mRNA will also be explored. The trial uses a staggered dosing schedule to ensure safety, with the first two participants in each group being dosed before the remaining participants. If no significant safety issues are observed, the remaining participants will receive their doses.
Eligibility
Inclusion Criteria14
- 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.
Exclusion Criteria19
- 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.
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Interventions
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.
Locations(1)
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ACTRN12625000800426