Efficacy and Safety of Oral Salmon Calcitonin in Patients With Knee Osteoarthritis (OA 2 Study)

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: Oral Salmon Calcitonin
* Drug: Oral Salmon Calcitonin (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 | Drug: Oral Salmon Calcitonin<br>* 0.8mg SMC021, twice daily<br>|
| Placebo Comparator: 2<br>SMC021 Placebo | Drug: Oral Salmon Calcitonin (Placebo)<br>* 0.8mg Placebo, 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 Tibia-femoral Knee Joint in the Signal Knee Measured by X-ray Change From Baseline Over 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 | 
| Pain Subscore Change From Baseline Over 24 Months as Assessed by Western Ontario and McMaster Universities Arthritis (WOMAC) Index | 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 pain 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone & Cartilage Metabolism Biochemical Marker Change (Percentage). | The central laboratory analyzed serum CTX-I (S-Crosslaps, Elecsys) and osteocalcin as well as urine CTX I/creatinine and CTX-II/creatinine. These biomarkers were analysed in order to assess the cartilage and bone turonver ratio to baseline at month 24. | From baseline to 24 months | 
| Knee Disease Progression Assessed by MRI | Knee cartilage volume and thickness was assessed by MRI in 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 12 and month 24 | 
| Questionnaire to Assess Function and Physical Activity | Function and physical activity were assessed by assessed by WOMAC function sub-score in the signal knee. The criteria for assessment of the functional classification according to the American Rheumatism Association (ARA) were as follows (Hochberg et al 1992): I. Completely able to perform usual activities of daily living (self-care, vocational and avocational) II. Able to perform usual self-care and vocational activities, but limited in avocational activities. III. Able to perform usual self-care activities, but limited in vocational and avocational activities. IV. Limited ability to perform usual self-care activities, vocational and avocational activities. Self-care activities included dressing, feeding, bathing, grooming, and toileting. Avocational (recreational and/or leisure) and vocational (work, school, homemaking) activities were patient-desired and age- and sex-specific. | From baseline to months 1, 6, 12 and 24 | 
| Questionnaire to Assess Stiffness in the Signal Knee. | WOMAC's stiffness subscore was used to assess the stiffness 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 joint stiffness for when performing each daily function listed in the questionnaire. 0 is no stiffness (best), 100 is extreme stiffness (worst). The total function sub score for the questions are then calculated. Total possible minimum sub score is 0, maximum is 200. The final outcome is the absolute change from baseline to 24 months. If the outcome is less that 0 there is improvement (less stiffness). Patients were instructed not to take analgesics for 3 days prior to the WOMAC test. | Baseline to month 24 | 
| Questionnaire to Assess Health-related Quality of Life | Health-related quality of life was assessed by the EQ-5D questionnaire, which is a patient questionnaire for measure of health, developed by the EuroQol Group.The EQ-5D questionnaire was administered to patients in order to measure change in health-related quality of life (HRQoL) over 2 years. The subjects marks on a VAS scale from 0 to 100 the number that best describes their health today (0 is worst imaginable health state and 100 is best imaginable health state). The change from baseline in the EQ-5D VAS was calculated. | From baseline to month 24 | 
| Questionnaire to Assess Pain | Pain was assessed by the WOMAC subscore in the signal knee by visit. Patients assessed their current pain level using a 100 mm visual analogue scales (VAS) by placing an X on the line that best describes his/her pain, where 0 equaled No Pain and 100 equaled Worst Pain Imaginable. Patients were instructed not to take analgesics for 3 days prior to the VAS. | Baseline, month 1, month 6, month 12, 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