Efficacy and Safety of Oral Salmon Calcitonin in Patients With Knee Osteoarthritis

Study Overview
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Brief Summary
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The purpose of this Phase III study is to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of patients with osteoarthritis of the knee.

Official Title
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A Randomized, Double-Blind, Multi-Center, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Salmon Calcitonin in the Treatment of Subjects With Knee Osteoarthritis

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: SMC021 Oral Calcitonin
* Drug: SMC021 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medical history and symptoms of knee osteoarthritis Exclusion Criteria: Any other disease or medication affecting the bone or cartilage. Any clinical signs or laboratory evidence diseases, which in the Investigator's opinion would preclude the participant from adhering to the Protocol or completing the trial. Other protocol defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 51 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>SMC021 Oral Calcitonin, 0.8 mg twice daily during 24 months | Drug: SMC021 Oral Calcitonin<br>* 0.8mg SMC021 (Oral Calcitoinin) twice daily<br>|
| Placebo Comparator: 2<br>SMC021 Placebo, orally twice daily during 24 months | Drug: SMC021 Placebo<br>* Placebo orally, twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint Space Width (JSW) in the Medial Tibiofemoral Knee Joint in Signal Knee Measured by X-ray After 24 Months. | The signal knee was chosen prior to randomization based on which knee met the inclusion and exclusion criteria. The JSW is the space measured in mm between the 2 bones in the knee joint and this is assessed by x-ray. The JSW decreases with disease progression. The lower limit for participation in the trial were 2 mm JSW. There were no upper limit as long as inclusion and exclusion criteria were met. The outcome was measured as a change in JSW from baseline to month 24. | Change from baseline to 24 months | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscore in the Signal Knee | WOMAC is a self-administered set of standardized questionnaires to evaluate the condition of patients with osteoarthritis of the knee. The subject marks on a scale (1-100) the pain associated with performing each daily activity listed in the questionnaire. 0 is no pain (best), 100 is extreme pain (Worst). The total function sub score for the questions are then calculated. Total possible minimum sub score is 0, maximum is 500. The final outcome is the absolute change from baseline to 24 months. If the outcome is less that 0 there is improvement (less pain). | Change from baseline to 24 months | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Subscore in the Signal Knee. | WOMAC is a self-administered set of standardized questionnaires to evaluate the condition of patients with osteoarthritis of the knee. The subject marks on a scale (1-100) the degree of difficulty for performing each daily function listed in the questionnaire. 0 is no difficulty (best), 100 is extreme difficulty (worst). The total function sub score for the questions are then calculated. Total possible minimum sub score is 0, maximum is 1700. The final outcome is the absolute change from baseline to 24 months. If the outcome is less that 0 there is improvement (less difficulty). | Change from baseline to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Biochemical Markers of Bone & Cartilage Metabolism. | The central laboratory analyzed serum CTX-I (S-Crosslaps, Elecsys) and osteocalcin as well as urine CTX-I/creatinine and CTX-II/creatinine. It was originally planned that serum CTX-II would be measured, but this was not done. | From Baseline to Month 24 | 
| Effect on Hand Osteoarthritis (OA) Assessed by X-ray & Questionnaire From Baseline to 24 Months | To assess disease progression of OA affected joints, X-rays of both hands were performed & assessed by two central readers (at Synarc). Hand OA was assessed by calculating total score for osteophytes, cyst erosion, & joint space narrowing, each of which were based on sum of left and right hand X-ray analysis with possible scores of 0-66. The overall total score (possible range 0-198) was also used. Higher scores (closer to 66 or to 198 when using overall total score) imply a worse outcome. Hand analyses were based on double readings, and the mean was used in the analyses. The AUStralian/CANadian Osteoarthritis Hand Index (AUSCAN) questionnaire was also used for assessment of hand OA. It measures pain (5 questions), stiffness (1 question) and difficulties with daily activities (9 questions) through a visual analogue scale (0-100mm; 0 = lowest score; 100 = highest score). Lower AUSCAN scores represent a better outcome. Change (from baseline to month 24) in these scores was calculated. | Baseline and Month 24 | 
| Nature and # of AEs Monitored Continuously During Study | Adverse events were by system organ class of all patients. | From Baseline to Month 24 | 
| Disease Progression in the Knee Evaluated by MRI. | Disease progression in the signal knee (cartilage volume and thickness) were evaluated by magnetic resonance imaging (MRI). MRIs were performed for patients from the sites in Ballerup, Denmark, the Czech Republic, and Romania using a quality controlled low-field 0.18T C-Span scanner from Esaote dedicated to the imaging of extremities. The same solenoid coil was used for all patients at a given site. | From Baseline to Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, oral salmon calcitonin, treatment, efficacy, tolerability