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

Phase 3

Terminated

Conditions: Osteoarthritis

Interventions: Drug: Oral Salmon Calcitonin
Drug: Oral Salmon Calcitonin (Placebo)

Registration Number: NCT00704847

Lead Sponsor: Nordic Bioscience A/S

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1030

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Oral Salmon Calcitonin	SMC021 Oral Calcitonin
2	Oral Salmon Calcitonin (Placebo)	SMC021 Placebo

Primary Outcome Measures

Name	Time	Method
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	Change from baseline to 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.
Pain Subscore Change From Baseline Over 24 Months as Assessed by Western Ontario and McMaster Universities Arthritis (WOMAC) Index	Change from baseline to 24 months	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).

Secondary Outcome Measures

Name	Time	Method
Bone & Cartilage Metabolism Biochemical Marker Change (Percentage).	From baseline to 24 months	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.
Knee Disease Progression Assessed by MRI	From baseline to month 12 and month 24	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.
Questionnaire to Assess Function and Physical Activity	From baseline to months 1, 6, 12 and 24	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.
Questionnaire to Assess Stiffness in the Signal Knee.	Baseline to month 24	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.
Questionnaire to Assess Health-related Quality of Life	From baseline to month 24	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.
Questionnaire to Assess Pain	Baseline, month 1, month 6, month 12, month 24	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.

Trial Locations

Locations (18): CCBR Poland
🇵🇱
Warsaw, Poland
CCBR Czech
🇨🇿
Pardubice, Czechia
Little Common Surgery
🇬🇧
Bexhill-on-Sea, East Sussex, United Kingdom
Thurston Arthritis Research Center
🇺🇸
Chapel Hill, North Carolina, United States
Northwestern Center for Clinical Research
🇺🇸
Chicago, Illinois, United States
Centrum Osteoporozy i Chorób Kostno Stawowych, ul. Waryńskiego 6/2
🇵🇱
Bialystok, Poland
CCBR Vejle
🇩🇰
Vejle, Denmark
Centre de Rhumatologie St-Louis
🇨🇦
Sainte-Foy (Québec), Canada
Hospital Universitario de la Paz
🇪🇸
Madrid, Spain
Hospital Universitaire St. Luc, UCL 5390
🇧🇪
Brussels, Belgium
CCBR Ballerup
🇩🇰
Ballerup, Denmark
CCBR Romania
🇷🇴
Bucharest, Romania
Midwest Pharmaceutical Research
🇺🇸
Saint Peters, Missouri, United States
CCBR Aalborg
🇩🇰
Aalborg, Denmark
Achieve Clinical Research, LLC
🇺🇸
Tuscaloosa, Alabama, United States
Center for Healthy Aging
🇺🇸
Sacramento, California, United States
Rheumatology Clinical Research Unit
🇺🇸
Beachwood, Ohio, United States
CCBR Hong Kong
🇭🇰
Hong Kong, Hong Kong