Efficacy and Safety of Intramuscular Methylprednisolone Acetate in Hand Osteoarthritis: A Randomized, Placebo-Controlled Trial

The primary objective of this study is to assess the **efficacy** of intramuscular methylprednisolone acetate (120mg or 40mg) in reducing hand pain in patients with hand osteoarthritis, compared to placebo. This is measured using a digital 100mm Visual Analogue Scale (VAS) from baseline to week 4. This objective is clinically relevant as it aims to determine the potential of methylprednisolone in providing pain relief, which is a significant concern for patients with hand osteoarthritis.

Secondary objectives include:

• Investigating the non-inferiority of 40mg methylprednisolone compared to 120mg, contingent upon both doses demonstrating superiority to placebo.
• Comparing the three treatment arms based on various parameters such as changes in hand pain, hand function, grip strength, quality of life, and patient experience, among others, over a 48-week period.
• Exploring the association of baseline values with treatment response and developing a prediction model.
• Exploring subgroups based on structural changes observed in X-rays and other demographic factors.
• Assessing the safety of methylprednisolone by evaluating adverse events using standardized criteria.
• Evaluating the efficacy and safety of methylprednisolone based on cumulative dose received during the study.
• Identifying circulating biomarkers associated with response to methylprednisolone.

The clinical trial focuses on evaluating the efficacy of intramuscular **methylprednisolone acetate** in patients with **hand osteoarthritis**. The study population includes both male and female participants aged 45 years and older. Participants are required to have interphalangeal hand osteoarthritis, as confirmed by specific classification criteria, and must report hand pain greater than 40mm on a 100mm Visual Analogue Scale. Additionally, they should have experienced insufficient relief from at least one conventional pain medication, excluding paracetamol. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** and safety of intramuscular **methylprednisolone acetate** in patients with hand **osteoarthritis**. This is a randomized, double-blind, placebo-controlled trial, categorized as a Phase 3 study. The trial aims to assess the reduction in hand pain between baseline and week 4, using a digital 100mm Visual Analogue Scale (VAS). The study will compare two doses of methylprednisolone acetate (120mg and 40mg) against a placebo. The trial is expected to commence recruitment in July 2025 and conclude by May 2027, with a total duration of approximately 48 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age (≥45 years), hand pain (>40mm on VAS), and previous failure of conventional pain medication. Following successful screening, participants will be randomized into one of the treatment arms. Subsequent visits will include regular follow-up assessments to monitor hand pain reduction, functional improvement, grip strength, quality of life, and changes in systemic and local inflammation. These assessments will be conducted through patient-reported outcomes, imaging of structural joint changes, and analysis of inflammatory biomarkers.

The end-of-study visit will occur at the conclusion of the 48-week period, where final evaluations will be conducted to assess the long-term efficacy and safety of the treatment. Participant involvement is expected to last for the entire duration of the trial unless early termination is warranted. Conditions for early termination may include adverse events, withdrawal of consent, or non-compliance with study protocols. The trial will ensure that all procedures adhere to ethical standards and regulatory requirements, maintaining the integrity and scientific validity of the study outcomes.

The clinical trial involves the administration of **methylprednisolone acetate** as the experimental medication. The product, marketed under the name Depo-Medrol 40 mg/ml, is a **suspension for injection**. The active substance, methylprednisolone acetate, is of chemical origin and is provided by Pfizer B.V. The medication is administered via **intramuscular injection**. For the purposes of this study, the suspension is relabeled and blinded, with the 40 mg dose being combined three times to achieve a total of 120 mg in a single syringe. The maximum daily and total dose is 120 mg, and the treatment period is limited to one day.

The non-experimental treatment used in this study is a placebo, consisting of **sodium chloride** solution for injection, marketed as Natriumchloride 0.9% oplossing voor injectie. This solution is also of chemical origin and is provided by Fresenius Kabi Nederland B.V. The placebo is administered via intramuscular injection, with blinding and relabeling applied to maintain the integrity of the study. The maximum daily and total dose for the placebo is also 120 mg, with a treatment period of one day.

Both the experimental and placebo treatments are administered under controlled conditions, with compliance monitored throughout the study. The primary objective is to assess the efficacy of intramuscular methylprednisolone acetate in reducing hand pain in patients with hand osteoarthritis, compared to the placebo, as measured on a digital 100mm Visual Analogue Scale (VAS) over a four-week period.

The efficacy of intramuscular **methylprednisolone acetate** in patients with hand osteoarthritis will be assessed primarily by measuring the reduction in hand pain from baseline to week 4. This will be evaluated using a digital 100mm Visual Analogue Scale (VAS), comparing the effects of 120mg or 40mg doses of methylprednisolone acetate against a placebo. Secondary endpoints include evaluating the non-inferiority of the 40mg dose compared to the 120mg dose, provided both demonstrate superiority over placebo. Additional assessments will compare the three treatment arms based on hand pain reduction, functional improvement, grip strength, quality of life, and changes in systemic and local inflammation over a 48-week period.

Patient-reported outcomes, structural joint changes via imaging, and inflammatory biomarkers will be utilized to gather data. The study will also explore predictors of treatment response, subgroup variations based on radiographic findings, and safety outcomes using standardized criteria. The efficacy and safety of methylprednisolone acetate will be analyzed concerning cumulative dose and circulating biomarkers. These assessments will provide comprehensive insights into the treatment's impact on hand osteoarthritis.