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

• ClinicalTrials.gov Identifier: NCT00704847
• Recruitment Status: Terminated
• First Posted: June 25, 2008
• Results First Posted: September 12, 2012
• Last Update Posted: April 24, 2019
• Sponsor: Nordic Bioscience A/S
• Collaborator: Novartis
• Information provided by (Responsible Party): Nordic Bioscience A/S

Study Description

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

Condition or disease	Intervention/treatment	Phase
Osteoarthritis	Drug: Oral Salmon Calcitonin; Drug: Oral Salmon Calcitonin (Placebo)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1030 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: June 2008
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: June 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1; SMC021 Oral Calcitonin	Drug: Oral Salmon Calcitonin; 0.8mg SMC021, twice daily
Placebo Comparator: 2; SMC021 Placebo	Drug: Oral Salmon Calcitonin (Placebo); 0.8mg Placebo, twice daily

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 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.
2. Pain Subscore Change From Baseline Over 24 Months as Assessed by Western Ontario and McMaster Universities Arthritis (WOMAC) Index [ Time Frame: 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 :

1. Bone & Cartilage Metabolism Biochemical Marker Change (Percentage). [ Time Frame: 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.
2. Knee Disease Progression Assessed by MRI [ Time Frame: 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.
3. Questionnaire to Assess Function and Physical Activity [ Time Frame: 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.

4. Questionnaire to Assess Stiffness in the Signal Knee. [ Time Frame: 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.

5. Questionnaire to Assess Health-related Quality of Life [ Time Frame: 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.

6. Questionnaire to Assess Pain [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 51 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Achieve Clinical Research, LLC

Tuscaloosa, Alabama, United States, 35406

United States, California

Center for Healthy Aging

Sacramento, California, United States, 95817

United States, Illinois

Northwestern Center for Clinical Research

Chicago, Illinois, United States, 60611

United States, Missouri

Midwest Pharmaceutical Research

Saint Peters, Missouri, United States, 63376

United States, North Carolina

Thurston Arthritis Research Center

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Rheumatology Clinical Research Unit

Beachwood, Ohio, United States, 44122

Belgium

Hospital Universitaire St. Luc, UCL 5390

Brussels, Belgium, 1200

Canada

Centre de Rhumatologie St-Louis

Sainte-Foy (Québec), Canada, G1W 4R4

Czechia

CCBR Czech

Pardubice, Czechia, 53002

Denmark

CCBR Aalborg

Aalborg, Denmark, 9000

CCBR Ballerup

Ballerup, Denmark, 2750

CCBR Vejle

Vejle, Denmark, 7100

Hong Kong

CCBR Hong Kong

Hong Kong, Hong Kong

Poland

Centrum Osteoporozy i Chorób Kostno Stawowych, ul. Waryńskiego 6/2

Bialystok, Poland, 15-461

CCBR Poland

Warsaw, Poland, 04703

Romania

CCBR Romania

Bucharest, Romania, 030463

Spain

Hospital Universitario de la Paz

Madrid, Spain, 28046

United Kingdom

Little Common Surgery

Bexhill-on-Sea, East Sussex, United Kingdom, TN 39 4SP

Sponsors and Collaborators

Nordic Bioscience A/S

Novartis

Investigators

• Study Director: Bente Juel Riis, MD; Nordic Bioscience

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bihlet AR, Byrjalsen I, Bay-Jensen AC, Andersen JR, Christiansen C, Riis BJ, Valter I, Karsdal MA, Hochberg MC. Identification of pain categories associated with change in pain in patients receiving placebo: data from two phase 3 randomized clinical trials in symptomatic knee osteoarthritis. BMC Musculoskelet Disord. 2018 Jan 17;19(1):17. doi: 10.1186/s12891-018-1938-5.

Karsdal MA, Byrjalsen I, Alexandersen P, Bihlet A, Andersen JR, Riis BJ, Bay-Jensen AC, Christiansen C; CSMC021C2301/2 investigators. Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials. Osteoarthritis Cartilage. 2015 Apr;23(4):532-43. doi: 10.1016/j.joca.2014.12.019. Epub 2015 Jan 9.

Henriksen K, Bay-Jensen AC, Christiansen C, Karsdal MA. Oral salmon calcitonin--pharmacology in osteoporosis. Expert Opin Biol Ther. 2010 Nov;10(11):1617-29. doi: 10.1517/14712598.2010.526104. Epub 2010 Oct 11. Review.

• Responsible Party: Nordic Bioscience A/S
• ClinicalTrials.gov Identifier: NCT00704847 History of Changes
• Other Study ID Numbers: CSMC021C2302
• First Posted: June 25, 2008
• Results First Posted: September 12, 2012
• Last Update Posted: April 24, 2019
• Last Verified: April 2019

Keywords provided by Nordic Bioscience A/S:

Osteoarthritis, oral salmon calcitonin, treatment, efficacy,; tolerability

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Calcitonin; Salmon calcitonin; Calcitonin Gene-Related Peptide; Katacalcin; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents; Vasodilator Agents