Investigation of Growth Hormone and Platelet-Rich Plasma on Joint Health

This clinical study will evaluate the efficacy and safety of intra-articular (IA) administration of recombinant human growth hormone (rhGH; somatropin) in combination with platelet-rich plasma (PRP) in adults with knee and ankle osteoarthritis resistant to conventional treatment. The investigational product will consist of 15 IU of somatropin combined with 10 mL of autologous PRP per injection.

The study, sponsored by Integrant Pty Ltd, will be conducted as a Phase IIb, multi-centre, double-blind, randomised, placebo-controlled, parallel-group superiority trial. Participants will be randomised 1:1 to receive either rhGH + PRP or volume-matched saline placebo. The primary site is St John of God Subiaco, with RegenU Clinics in Potts Point as the secondary site.

The study will recruit 192 participants, comprising 96 participants in the knee cohort and 96 participants in the ankle cohort. Within each cohort, 48 participants will receive rhGH + PRP and 48 will receive saline placebo. Participants will receive five IA injections into the affected knee or ankle joint, administered 7-16 days apart, over approximately 4-9 weeks. Injections will be performed under ultrasound guidance. Following each injection, participants in both treatment groups will undergo 20 minutes of non-invasive joint distraction.

Participants randomised to the placebo group will receive sterile normal saline (0.9% NaCl), volume-matched at approximately 10-12 mL per injection. To maintain the double-blind design, blood will also be collected from placebo participants for PRP preparation, but the blood will be discarded and the participant will receive saline only. Active and placebo preparations will be administered using identical opaque syringes and study-code labelling, with preparation performed by an independent unblinded clinical staff member. Participants, treating clinicians and outcome assessors will remain blinded to treatment allocation.

The inclusion criteria include ankle or knee arthritis resistant to treatment in the GP clinic setting; radiographically confirmed cartilage injury with Kellgren-Lawrence grade 0-3 demonstrated on MRI or weight-bearing X-ray within six months of study application; ability to provide informed consent; and ability to attend required follow-up visits. Exclusion criteria include known hypersensitivity to any component of the product; cancer diagnosis or suspicion; active or resected tumour; skeletal immaturity; pregnancy or breastfeeding; active infection at the injection site; open soft-tissue injury; specified metabolic disorders affecting the skeleton; age over 70 years; unstable or malaligned joint greater than 5 degrees; severe osteoarthritis classified as Kellgren-Lawrence grade 4, including bone-on-bone joints with no detectable cartilage; hypersensitivity to citrate or somatropin; inability to provide informed consent; or inability to attend required follow-up visits.

The primary endpoint is the proportion of participants achieving treatment success at six months, defined as a ≥30% improvement from baseline in the joint-specific functional score compared with the control group. FAOS will be used for participants with ankle osteoarthritis and WOMAC for participants with knee osteoarthritis. Secondary assessments include clinical assessment of symptoms and function at three months and six months, as well as repeat MRI and X-ray imaging at six months.

Blood samples will be collected for HGH measurement, including samples taken before and two hours after each injection following the baseline assessment. These measurements will be used to assess systemic exposure and the local versus systemic pharmacodynamic effects of the intervention. Safety will also be monitored through adverse-event assessment, laboratory testing and ongoing independent medical review.

The study hypothesises that intra-articular rhGH combined with PRP, administered within the standardised joint-distraction protocol, will improve clinical outcomes in patients with treatment-resistant knee or ankle osteoarthritis compared with saline placebo. The study is intended to provide preliminary evidence of efficacy and safety and inform the design of a subsequent Phase III clinical trial.

Inclusion criteria

include:

• Ankle/Knee arthritis resistant to treatment in GP clinic setting.
• Radiographically confirmed cartilage injury with Kellgren-Lawrence grade 1-3 can be shown on MRI scan or weight bearing X-Ray within 6 months of study application.
• Able to give informed consent to participate in a clinical trial.
• Able to commit to attending a clinic for follow up.

Exclusion criteria

Known contraindications for ARTG registered somatropin from various manufacturers (Humatrope, Genotropin) have been used to guide the development of somatropin-related exclusion criteria.

Exclusion criteria

include:

• A known hypersensitivity to any of the components of the product.
• Cancer diagnosis or suspicion.
• Resected or active tumour.
• Skeletally immature (<18 years of age or no radiographic evidence of closure of epiphyses).
• Pregnancy/breastfeeding (participants of childbearing potential need negative pregnancy test in prior screening and agreed upon method of contraception throughout duration of study)
• Active infection at the injection site.
• Open soft tissue injury.
• Metabolic disorders known to adversely affect the skeleton (e.g. renal osteodystrophy or hypercalcemia), other than primary osteoporosis or diabetes.
• Over 70 years of age.
• Unstable joint or maligned joint > 5 degrees.
• Severe osteoarthritis (Kellgren-Lawrence grade 4 on baseline imaging), including bone-on-bone joints with no detectable cartilage.
• Known hypersensitivity to citrate or somatropin.
• Unable to give informed consent.
• Unable to commit to attend clinic for all follow ups.