Background/Purpose: To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen^® technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural damage classified as Kellgren-Lawrence 2-3.

Methods:  This is the combined reporting of two randomized, double-blind, multi-center, placebo-controlled trials (CSMC021C2301 and CSMC021C2302), evaluating the efficacy and safety of oral salmon calcitonin in patients with painful knee OA, enrolling 1,176 and 1,030 patients, respectively. The subjects had painful knee OA with structural manifestations. Study subjects were randomized (1:1) to oral sCT 0.8 mg twice daily or placebo (PBO) for 24 months. The primary efficacy objectives were to examine the treatment effect compared to placebo on change over 24 months in joint space width (JSW) in the signal knee measured by X-ray, and to examine the change in pain and function using the WOMAC questionnaire. Other study parameters included patient and physician global assessment, cartilage volume measured by MRI technology, and biochemical markers of bone resorption (CTX-I) and cartilage degradation (CTX-II). The primary safety objective was to characterize the safety and tolerability profile based on adverse events incidence and changes in laboratory profiles.

Results:  At the 24 month endpoint there was no statistically significant treatment effect on JSN in any of the two studies. In CSMC021C2301 there was a statistically significant (p<0.0001) treatment effect on WOMAC (sum of pain, function, stiffness, and total scores) as well as on the biomarkers of bone and joint metabolism (p=0.0003). None of the WOMAC scores or the biomarkers achieved a statistically significant treatment effect in the CSMC021C2302 study.

Conclusion: The present formulation of oral calcitonin did not provide reproducible clinical benefits in patients with symptomatic knee OA. (NCT00486434, NCT00704847).

ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatment-of-symptomatic-knee-osteoarthritis-with-oral-salmon-calcitonin-results-from-two-phase-3-randomized-clinical-trials/