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OsteoarthritisPhase 2NCT01160822

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

A Phase 2 study testing Canakinumab and Naproxen in people with Osteoarthritis, run by Novartis Pharmaceuticals at 13 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Osteoarthritis
What is being tested?
Canakinumab and Naproxen
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
169 participants
Where
13 sitesin 4 countries
Study dates
Apr 2010to Jul 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
Show all 9Show fewer
  • 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

Who cannot join

  • 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
Show all 24Show fewer
  • 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)
  • Presence of severe renal function impairment. History of renal trauma, glomerulonephritis, patients with one kidney, or renal failure requiring regular dialysis treatment.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive pregnancy test (serum or urine).
  • Subjects with known contra-indications to naproxen (e.g. heart or circulation problems, history of ulcer disease etc.), analgesics, antipyretics, or NSAIDs.
  • Disease of the spine or other lower extremity joints which may interfere with the assessment of the target joint.
  • Surgery on the knee within the last year. Observational arthroscopy, arthroscopic surgery or lavage of the knee within the last 6 months.
  • Use of assistive devices other than a cane (walking stick) or knee brace.
  • Subjects who have experienced, any time in the past, asthma, acute rhinitis, nasal polyps, angioneurotic edema, urticaria or other allergic-type reaction after taking acetylsalicylic acid (ASA)/ aspirin or NSAIDs.
  • Any history of prior peptic ulcer disease or prior NSAID gastrointestinal complications for the past 5 years.
  • Other protocol defined inclusion/exclusion criteria may apply.

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

United States8 sites
  • Pinnacle Research Group, LLC

    Anniston, Alabama, 36207

  • Rush-Presbyterian St. Lukes Medical Center

    Chicago, Illinois, 60612

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania, 16635

  • Volunteer Research Group

    Knoxville, Tennessee, 37920

  • Arizona Arthritis & Rheumatology Research, PLLC

    Mesa, Arizona, 85202

  • San Diego Arthritis & Osteoporosis Medical Clinic

    San Diego, California, 92108

  • Cotton O'Neil Clinical Research Institute

    Topeka, Kansas, 66606

  • Westlake Medical Research

    Westlake Village, California, 91361

Other trials in United States

Finland2 sites
  • Novartis Investigative site

    Helsinki

  • Novartis Investigative site

    Kuopio

Other trials in Finland

Germany2 sites
  • Novartis Investigative site

    Berlin

  • Novartis Investigative site

    Erlangen

Other trials in Germany

France1 site
  • Novartis Investigative site

    Créteil

Other trials in France

About this study

Official title: A Randomized, Double Blind, Placebo and Naproxen Controlled, Multi-center, Study 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

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.

Read the detailed description

This is a randomized, double-blind, parallel group, placebo controlled 18 weeks study, consisting of two parts:

  1. Part A: an ascending single dose part in which the safety and tolerability of up to 4 different canakinumab doses are studied (starting dose 150 mg, maximum dose 600 mg).
  2. Part B: a double-dummy, active-controlled, parallel design part in which the pain reduction of the canakinumab dose selected from part A is studied in comparison to Placebo and Naproxen.
Conditions
Osteoarthritis
Being tested
Canakinumab, Placebo to canakinumab, Naproxen, Placebo to Naproxen
Keywords
Osteo arthritis, pain control, intra- articular injections, Knee OA
Medical subject headings
Osteoarthritis, Agnosia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CanakinumabBiological

    Also called ACZ885

    Intra-articular injection

  • Placebo to canakinumabDrug

    Intra-articular injection

  • NaproxenDrug

    Tablets for oral administration

  • Placebo to NaproxenDrug

    Tablets for oral administration

Study groups in NCT01160822
Study groupRoleWhat they receive
Part A: CanakinumabExperimentalIn 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.
Receives: Biological: Canakinumab
Part A: PlaceboPlacebo comparatorParticipants received a single intra-articular injection of canakinumab-matching placebo.
Receives: Drug: Placebo to canakinumab
Part B: CanakinumabExperimentalParticipants received a single intra-articular injection of canakinumab on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.
Receives: Biological: Canakinumab; Drug: Placebo to Naproxen
Part B: PlaceboPlacebo comparatorParticipants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.
Receives: Drug: Placebo to canakinumab; Drug: Placebo to Naproxen
Part B: NaproxenActive comparatorParticipants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen 500mg tablets orally twice daily for 12 weeks.
Receives: Drug: Placebo to canakinumab; Drug: Naproxen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to Day 3

  2. 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.

    Measured: Baseline and Day 4

  3. 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.

    Measured: Baseline and Week 4

Secondary outcomes (21)
  1. Part B: Change From Baseline 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).

    Results are from a Bayesian ANCOVA model, fitting baseline pain VAS score as a covariate, time by treatment as fixed effects, region and patient as random effects.

    Measured: Baseline and Weeks 4, 8 and 12

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

    A responder is defined as a participant with a 50% or greater reduction from baseline on the VAS scale for pain assessment. 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).

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

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

    The WOMAC consists of 3 subscales:

    The Pain subscale asks patients to rate pain in the index knee joint in the last 48 hours during walking, using stairs, in bed, sitting or lying, and standing on a scale from none (0) to extreme pain (4). The answers are summed and the total pain subscale score ranges from 0-20.

    The Stiffness subscale assesses stiffness in the index knee joint during the last 48 hours doing different activities on a scale from none (0) to extreme stiffness (4). The total stiffness subscale score ranges from 0-8.

    The Physical Function subscale assesses difficulty performing daily physical activities during the last 48 hours on a scale from none (0) to extreme difficulty (4). The total physical function subscale score ranges from 0-68.

    Higher scores indicate more pain/stiffness/difficulty. Results are from a Bayesian ANCOVA model, with baseline WOMAC score as a covariate, time by treatment as fixed effects, region and patient as random effects.

    Measured: Baseline and Weeks 4, 8 and 12

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

    Participants were permitted to take oral rescue medication (Acetaminophen ≤ 4 gram/day) up until 24 hours of a scheduled assessment visit during the 12-week treatment period. The estimates shown are the Kaplan-Meier estimates of the proportion of participants that took rescue medication.

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

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

    Participants made a global assessment of their response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Day 4

  6. Patient's Global Assessment of Response to Treatment at Week 2

    Participants made a global assessment of their response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Week 2

  7. Patient's Global Assessment of Response to Treatment at Week 4

    Participants made a global assessment of their response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Week 4

  8. Patient's Global Assessment of Response to Treatment at Week 8

    Participants made a global assessment of their response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Week 8

  9. Patient's Global Assessment of Response to Treatment at Week 12

    Participants made a global assessment of their response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Week 12

  10. Part B: Physician's Global Assessment of Response to Treatment at Day 4

    The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Day 4

  11. Part B: Physician's Global Assessment of Response to Treatment at Week 2

    The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Week 2

  12. Part B: Physician's Global Assessment of Response to Treatment at Week 4

    The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Week 4

  13. Part B: Physician's Global Assessment of Response to Treatment at Week 8

    The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Week 8

  14. Part B: Physician's Global Assessment of Response to Treatment at Week 12

    The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

    Measured: Week 12

  15. Maximum Observed Plasma Concentration of Canakinumab (Cmax)

    Measured: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

  16. Time to Reach the Maximum Observed Plasma Concentration of Canakinumab (Tmax)

    Measured: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

  17. Area Under the Concentration Time Curve up to the Last Measurable Concentration (AUClast)

    Measured: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

  18. Area Under the Concentration Time Curve From Time Zero to Infinity AUC(0-inf)

    Measured: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

  19. Terminal Phase Half-life (t1/2) of Canakinumab

    The time it takes for the concentration level of canakinumab to fall to 50% of the original value.

    Measured: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

  20. Apparent Clearance of Canakinumab From Plasma (CL/F)

    Measured: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

  21. Apparent Volume of Distribution During Terminal Phase (Vz/F)

    Measured: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2010 (estimated)
  2. Study startApr 2010
  3. Primary completionJul 2011
  4. Study completionJul 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
169 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01160822
Sponsor's protocol ID
CACZ885C2201
Other IDs
2009-015017-48, 2009
Status last verified
Sep 2012
First submitted
9 Jul 2010
Last updated
30 Oct 2012

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Canakinumab and Naproxen in people with Osteoarthritis, run by Novartis Pharmaceuticals at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Finland, Germany, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With Intolerance Events (time frame: Baseline to Day 3). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2012.

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