To Determine the Safety, Tolerability, Pharmacokinetics and Effect on Pain of a Single Intra-articular Administration of Canakinumab in Patients With Osteoarthritis in the Knee

NCT01160822 | Completed Phase 2 Results

• 2 other identifiers: CACZ885C22012009-015017-48
• Study Type: interventional
• Target: 169
• Locations: 4 countries
• Sites: 13

Brief Summary

The purpose of this study was to determine whether, in patients with mild to moderate knee osteoarthritis, canakinumab is safe and tolerable when injected intra-articularly.

Conditions

Osteoarthritis

Keywords

Osteo arthritis; pain control; intra- articular injections; Knee OA

Outcome Measures

Primary Outcomes (3)

• Part A: Number of Participants With Intolerance Events

  An intolerance event is defined as an acute inflammatory reaction, characterized by a 30 mm increase in pain (on a 100 mm visual analog scale (VAS) and associated with a new or worsened synovial fluid effusion within 3 days following the intra-articular (i.a.) injection. If baseline VAS pain score is ≥ 70 mm, an intolerance event is defined as an increase in pain by 20 mm on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection. If baseline VAS pain score is ≥ 80 mm, an intolerance event is defined as an increase in pain by 10 mm on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection. If baseline pain score is ≥ 90 mm, an intolerance event is defined as the patients experiencing an unspecified increase in pain on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection.

  Baseline to Day 3

• Part B: Change From Baseline to Day 4 in Pain Using 100 mm Visual Analog Scale (VAS)

  After walking for 20 meters, participants were asked to assess the pain in their affected knee on a 100 mm linear visual analog scale ranging from no pain (0 mm) to unbearable pain (100 mm). A negative change from Baseline score indicates improvement. Results are from a Bayesian analysis of covariance (ANCOVA) model, fitting baseline pain VAS score as a covariate, time by treatment as fixed effects, region and subject as random effects.

  Baseline and Day 4

• Part B: Change From Baseline to Week 4 in Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain Subscale

  The Western Ontario and McMaster osteoarthritis Index (WOMAC) pain subscale asks patients to rate pain in the index knee joint in the last 48 hours doing different activities on a scale from none (0) to extreme pain (4). The answers are summed and the total pain subscale score ranges from 0 to 20, where higher scores indicate more pain. A negative change from Baseline score indicates improvement. Results are from a Bayesian ANCOVA model, fitting baseline WOMAC pain score as a covariate, time by treatment as fixed effects, region and patient as random effects.

  Baseline and Week 4

Secondary Outcomes (21)

• Part B: Change From Baseline in Pain Using 100 mm Visual Analog Scale (VAS)

  Baseline and Weeks 4, 8 and 12

• Part B: Percentage of Responders in the Pain 100 mm Visual Analog Scale (VAS)

  Baseline, Day 4, Weeks 1, 2, 4, 8 and 12

• Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales

  Baseline and Weeks 4, 8 and 12

• Part B: Proportion of Participants Who Used Rescue Analgesic During Study

  Day 4, Weeks 1, 2, 4, 8 and 12

• Patient's Global Assessment of Response to Treatment on Day 4

  Day 4

Study Arms (5)

Part A: Canakinumab

EXPERIMENTAL

In this ascending dose part, participants received a single intra-articular injection of canakinumab. The beginning dose was 150 mg, escalating to the 300 mg dose and then to 600 mg.

Biological: Canakinumab

Part A: Placebo

PLACEBO COMPARATOR

Participants received a single intra-articular injection of canakinumab-matching placebo.

Drug: Placebo to canakinumab

Part B: Canakinumab

EXPERIMENTAL

Participants received a single intra-articular injection of canakinumab on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.

Biological: Canakinumab; Drug: Placebo to Naproxen

Part B: Placebo

PLACEBO COMPARATOR

Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.

Drug: Placebo to canakinumab; Drug: Placebo to Naproxen

Part B: Naproxen

ACTIVE COMPARATOR

Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen 500mg tablets orally twice daily for 12 weeks.

Drug: Placebo to canakinumab; Drug: Naproxen

Interventions

Canakinumab BIOLOGICAL

Intra-articular injection

Also known as: ACZ885

Part A: Canakinumab; Part B: Canakinumab

Placebo to canakinumab DRUG

Intra-articular injection

Part A: Placebo; Part B: Naproxen; Part B: Placebo

Naproxen DRUG

Tablets for oral administration

Part B: Naproxen

Placebo to Naproxen DRUG

Tablets for oral administration

Part B: Canakinumab; Part B: Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Male and female patients aged 40 - 80 years (inclusive).
• Diagnosis of knee osteoarthritis
• Radiographic evidence of tibiofemoral compartment osteoarthritis
• Pain in the knee during the last 24 hours.The patients should also have had pain in the affected knee on most days over the last month.
• Patients who are willing to discontinue all non-steroidal anti-inflammatory drugs (NSAIDs) or other analgesic medication taken for any condition, including their knee pain,
• Patients who are on stable dose of opioids for at least 1 month before screening can continue to take their opioid at this stable dose throughout the study.
• Patients must also be willing to abstain from any intra-articular or peri-articular injections to the knee or surgery during the treatment period
• Patients who, if they are currently taking aspirin (325 mg/day or less; as anti-coagulants), are willing to remain on a stable dose one month prior to screening and throughout the study

You may not qualify if:

• Subjects with known hypersensitivity to any biological or investigational drugs.
• Patients with contraindications to knee injections
• Patients with joint effusion
• Patients should not have rheumatoid arthritis or any connective tissue like disease
• Secondary osteoarthritis with history and/or any evidence of the following diseases: septic arthritis, inflammatory joint disease, gout, Paget's disease of the bone, articular fracture, major dysplasias or congenital abnormality, ochronosis, acromegaly, hemochromatosis, Wilson's disease, primary osteochondromatosis, juvenile chronic arthritis with continued activity in adulthood, heritable disorders (e.g. hypermobility). Patients with secondary osteoarthritis following menisectomy or injuries of a collateral or cruciate ligament are not excluded.
• Presence or history of underlying metabolic, endocrine, hematologic, pulmonary, cardiac, blood, renal, hepatic, infectious, psychiatric or gastrointestinal conditions
• Evidence of tuberculosis (TB)
• One of the risk factors for TB such as:
• Substance abuse (e.g. injection or non-injection)
• Health-care workers with unprotected exposure to patients who are at high risk of TB
• Patients with TB disease before the identification and correct airborne precautions of the patient
• close contact (i.e. share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)) with a person with active pulmonary TB disease.
• Significant medical problems, including but not limited to the following: uncontrolled hypertension,congestive heart failure, uncontrolled diabetes type I and II
• Subjects with evidence of hepatic or blood coagulation disorders (i.e. hemophilia, etc), anemia, idiopathic thrombocytopenic purpura, or gastrointestinal disorder: severe hepatic disease, history of alcohol and drug abuse; disease of gall bladder and pancreas; active peptic ulceration, gastrointestinal bleeding or history of severe gastro-esophageal reflux disease or severe hiatus hernia; inflammatory bowel disease.
• Use of any therapeutic protein drug (e.g. anti-tumor necrosis factor alpha (TNFα) antibody)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Pinnacle Research Group, LLC

Anniston, Alabama, 36207, United States

Location

Arizona Arthritis & Rheumatology Research, PLLC

Mesa, Arizona, 85202, United States

Location

San Diego Arthritis & Osteoporosis Medical Clinic

San Diego, California, 92108, United States

Location

Westlake Medical Research

Westlake Village, California, 91361, United States

Location

Rush-Presbyterian St. Lukes Medical Center

Chicago, Illinois, 60612, United States

Location

Cotton O'Neil Clinical Research Institute

Topeka, Kansas, 66606, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

Novartis Investigative site

Helsinki, Finland

Location

Novartis Investigative site

Kuopio, Finland

Location

Novartis Investigative site

Créteil, France

Location

Novartis Investigative site

Berlin, Germany

Location

Novartis Investigative site

Erlangen, Germany

Location

MeSH Terms

Conditions

Osteoarthritis; Agnosia

Interventions

canakinumab; Naproxen

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2010
• First Posted: July 12, 2010
• Study Start: April 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: October 30, 2012
• Results First Posted: August 30, 2012

Record last verified: 2012-09

Locations

FI (2); DE (2); US (8); FR (1)