Assessing Clodronate for Painful Knee Osteoarthritis

Adaptative, Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled, Clinical Trial, on the Efficacy and Tolerability of Different Escalating Doses of Intra-articular Clodronate in Patients With Painful Knee Osteoarthritis

This study is testing different doses of clodronate to see if it can help people with painful knee osteoarthritis feel better compared to a placebo.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 296 (estimated)
• Ages: 50 Years to 75 Years
• Sex: All
• Sponsor: SPA Società Prodotti Antibiotici S.p.A. (Industry-sponsored)
• Drugs / interventions: Denosumab
• Locations: 11 sites (Castel Goffredo, Mantova and 10 other locations)
• Trial ID: NCT06263517 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine the optimal dose of clodronate for treating painful knee osteoarthritis (OA) through a two-phase approach. In Phase II, the safety and tolerability of escalating doses of intra-articular clodronate will be evaluated, leading to the selection of a defined therapeutic dose (DTD). Phase III will then confirm the efficacy and safety of this DTD compared to a placebo in a larger patient population. The study will involve multiple centers and a randomized, double-blind design to ensure robust results.

Who should consider this trial

Good fit: Ideal candidates are men and women aged 50 to 75 with symptomatic knee OA and a specific pain level.

Not a fit: Patients with a BMI over 35 kg/m² or joint instability from causes other than knee OA may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide an effective treatment option for patients suffering from painful knee osteoarthritis.

How similar studies have performed: While this approach is being tested in this trial, similar studies have shown promise in evaluating intra-articular treatments for osteoarthritis.

Eligibility criteria

Inclusion Criteria:

* Female and male patients aged 50 up to 75 years at ICF signature.
* Diagnosis of knee OA according to the American College of Rheumatology, confirmed by Rx during the screening (a Rx performed in the last 3 months before Baseline is accepted).
* Kellgren-Lawrence radiographic score between 2 and 3 degrees in the tibiofemoral joint.
* Symptomatic knee OA (pain) since at least 6 months with a knee pain (VAS) ranging between 40 and 80 mm at Screening visit (the figure should be confirmed at Baseline).
* Female patients of childbearing potential must have a negative pregnancy test before each treat-ment and during the Visit 5 - Week 4 and they must use adequate methods of contraception throughout the course of the study.
* A signed ICF by the patient after exhaustive study discussion with the investigators.

Exclusion Criteria:

* BMI \> 35 kg/m² (Class II obesity).
* Joint instability due to other reasons than knee OA, such as f.i. algo dystrophic syndrome, either partial or complete rupture of internal / externals ligaments, kneecap instability, etc.
* Otherwise located lower limb pain, such as hip pain.
* Other musculoskeletal disorders related to the target knee.
* Any treatment with IA drugs in the last 3 months before Day 0 - Baseline (including any formulation of corticosteroids or hyaluronic acid injections).
* Corticosteroid use by any systemic route, and hyaluronic acid injection or intraarticular corticosteroids for any other joint in the previous month will not be permitted.
* Any treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) in the week before enrolment, or any steroid anti-inflammatory drugs and chondroprotective drugs in the thirty (30) days before month before Baseline.
* Any treatment with systemic bisphosphonates in the last twelve (12) months before Baseline.
* Any treatment with Glucosamine or Chondroitin sulfate, Diacerein and Matrix metalloproteinase (MMP) inhibitors in the 4 weeks before Baseline.
* Any treatment with Denosumab in the twelve (12) months before Baseline.
* Any treatment with Paracetamol in the twelve (12) hours before Baseline.
* Any knee surgery in the past or knee arthroplasty.
* Any diagnostic or surgical arthroscopy of the knee in the six (6) months before Baseline.
* Any jaw osteonecrosis in the last twenty-four (24) months before Baseline or at a risk of jaw osteonecrosis.
* Any known hypersensitivity to the drug in the study to its excipients or other bisphosphonates, and any hypersensitivity to Paracetamol (rescue drug).
* Any participation in a clinical study in which the last administration of the investigational medicinal product was within two (2) weeks before consenting to study participation (i.e.signing ICF).
* Inadequate organ function defined by the following laboratory parameters:

  1. Absolute Neutrophil Count (ANC) \< 1500/μl.
  2. Hemoglobin (Hb) \< 9 g/dl (\< Hb 5.6 mmol/L)
  3. Platelet Count \< 100.000/μl
  4. Serum Creatinine \> 1.5 x Upper limit normal (ULN) or estimated Glomerular Filtration Rate (eGFR) \< 60 mL/min (as per Cockroft-Gault formula).
  5. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST)\> 1.5 x Upper limit normal(ULN).
  6. Serum Total Bilirubin \> 1.5 x Upper limit normal (ULN).
* Pregnant or breastfeeding women, or women planning to become pregnant during the study.
* Any positive or suspected history of alcoholism or drug use.
* Clinically significant (i.e.) gastrointestinal, renal, hepatic, pulmonary, cardiovascular or neurological disease that could interfere with the outcome of the study or the patient's ability to comply with study requirements.
* Patients unwilling or unable to comply with the protocol.

Where this trial is running

Castel Goffredo, Mantova and 10 other locations

• IRCCS Istituti Clinici Maugeri — Castel Goffredo, Mantova, Italy (Recruiting)
• Ospedale San Pellegrino — Castiglione delle Stiviere, Mantova, Italy (Recruiting)
• Ospedale Civile Servizio di Riabilitazione Funzionale — Volta Mantovana, Mantova, Italy (Recruiting)
• Azienda Ospedaliera Universitaria San Luigi Gonzaga — Orbassano, Torino, Italy (Not_yet_recruiting)
• Centro Riabilitativo Polifunzionale Teresio Borsalino — Alessandria, Italy (Recruiting)
• IRCCS Ospedale Policlinico San Martino — Genova, Italy (Recruiting)
• Ospedale Israelitico — Roma, Italy (Recruiting)
• Ospedale San Pietro — Rome, Italy (Recruiting)
• Ospedale San Paolo — Savona, Italy (Not_yet_recruiting)
• Azienda Ospedaliero Universitaria Senese — Siena, Italy (Recruiting)
• Ospedale Policlinico "G.B. Rossi" Borgo Roma — Verona, Italy (Recruiting)

Study contacts

• Study coordinator: Maria Rosa Galmozzi

Conditions Osteoarthritis of Knee; Osteoarthritis