Osteoarthritis of the Knee, Inflammation, and the Effect of Adalimumab (OKINADA)

NCT02471118 | Completed Phase 2

• 1 other identifier: IMM 11-0024
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 7

Brief Summary

This is a Canadian randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the clinical efficacy and safety of adalimumab versus placebo when used to treat subjects with a diagnosis of osteoarthritis of the knee, and with clinical features of inflammation, whose pain persists despite receiving maximum tolerated doses of conventional therapy.

Conditions

Osteoarthritis, Knee

Keywords

Inflammatory Type

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint: the percentage of subjects achieving an Osteoarthritis Research Society International/Outcome Measures in Rheumatology Clinical trials (OARSI/OMERACT) response at Week 16

  The primary efficacy outcome measure will be the percentage of subjects achieving an OARSI/OMERACT response at Week 16.

  16 weeks

Secondary Outcomes (11)

• Secondary endpoint Knee Injury and Osteoarthritis Outcome (KOOS) composite pain score at 16 weeks.

  16 weeks

• Secondary endpoint KOOS composite pain 20/50 response rates

  16 weeks

• Secondary Endpoint KOOS activities of daily living score

  16 Weeks

• Secondary Endpoint KOOS symptoms score

  16 weeks

• Secondary Endpoint KOOS sport and recreation function score

  16 weeks

Study Arms (2)

1st 50 subjects to Enter the Study

EXPERIMENTAL

At Baseline, subjects will be randomized (1:1) to receive study drug (Adalimumab or placebo). The study drug will be provided as a subcutaneous injection (pre-filled syringe) either Adalimumab (ADA) 40 mg/0.8 mL,every other week (EOW) or matching placebo for Adalimumab every other week for 16 weeks. Efficacy will be assessed at Week 16 while the safety of the study drug will be monitored throughout the study. At Week 16 all subjects will begin to receive open label ADA 40 mg EOW and will continue to receive open label ADA up to Week 50. An End of Study visit will be done at Week 52. A Telephone Follow-up will be done at Week 62 to review Adverse Events and Concomitant Medications.

Drug: Adalimumab 40 mg; Drug: Placebo

2nd group of 50 subjects

EXPERIMENTAL

At Baseline, subjects will be randomized (1:1) to receive either adalimumab 40 mg every other week or placebo for 16 weeks. All subjects will begin to receive open label adalimumab 40 mg every other week from week 16-week 30, with An End of Study visit at Week 32. A Telephone Follow-up will be done at Week 42 to review Adverse Events and Concomitant Medications.

Drug: Adalimumab 40 mg; Drug: Placebo

Interventions

Adalimumab 40 mg DRUG

Adalimumab will be self-administered via subcutaneous (SC) injection

Also known as: Humira

1st 50 subjects to Enter the Study; 2nd group of 50 subjects

Placebo DRUG

Placebo will be self-administered via subcutaneous (SC) injection

1st 50 subjects to Enter the Study; 2nd group of 50 subjects

Eligibility Criteria

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

You may qualify if:

• ≥ 40 years of age
• If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing methods of birth control.
• If female and of childbearing potential, serum pregnancy results must be negative at Screening
• Has a diagnosis of Osteoarthritis (OA) of the index knee according to American College of Rheumatology (ACR) criteria, including radiological evidence of OA (Kellgren-Lawrence grades 2 or 3).
• Subject has had knee pain for at least 1 month prior to the Screening Visit.
• Subject has had knee pain that has persisted despite conventional treatment, defined as any one of the following medications taken for at least 1 month in the past:
• acetaminophen (2- 4 grams per day)
• therapeutic dose range of an NSAID
• acetaminophen/codeine combination (i.e. Tylenol No. 2, 3, 4) taken at least 3 times daily.
• Has a pain score of ≥ 4 (0-10 NRS) in the index (more symptomatic) knee at Screening and Baseline.
• If the subject is taking Analgesic/NSAIDs, then the Analgesic/NSAIDs has been stable for 14 days prior to the Baseline visit.
• Has clinical evidence of a knee effusion in the index (more symptomatic) knee at Screening and Baseline.
• Able and willing to self-administer SC injections or has available qualified person(s) to administer SC injections.
• Has voluntarily signed and dated an approved informed consent form prior to any study-specific procedures.

You may not qualify if:

• Has a history of an allergic reaction or significant sensitivity to constituents of adalimumab.
• Has other bone and articular diseases (antecedents and/or current signs) such as chondrocalcinosis, Paget's disease of the ipsilateral limb to the target knee, rheumatoid arthritis, aseptic osteonecrosis, gout, septic arthritis, ochronosis, acromegaly, haemochromatosis, Wilson's disease, osteochondromatosis, seronegative spondylo-arthropathy, mixed connective tissue disease, collagen vascular disease, psoriasis, inflammatory bowel disease.
• Subject has a BMI over 40.
• Planned/anticipated surgery of the index knee during the study period.
• Already scheduled for any surgery during the time of the study or within 70 days after the end of treatment.
• Prior arthroscopic or open surgery of the index knee within 12 months of Baseline.
• Has a history of cancer or lymphoproliferative disease other than: Successfully and completely treated cervical dysplasia, with no recurrence within the last five years, Basal or Squamous Cell Carcinoma that has been adequately treated or excised.
• Has had prior treatment with intravenous (IV) immunoglobulin or any investigational agent within 30 days or 5 half-lives of the agent from Baseline, whichever is longer.
• History of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease (e.g. multiple sclerosis).
• History of uncontrolled diabetes, unstable ischemic heart disease, active congestive heart failure, New York Heart Association (NHYA) III, IV, inflammatory bowel disease, active peptic ulcer disease, recent stroke (within 12 weeks of Screening), or any other condition, which in the opinion of the investigator, would put the patient at risk by participating in the study.
• Has concurrent local or systemic infection that would preclude the use of adalimumab.
• Has had a persistent or severe infection(s) requiring hospitalization or treatment with IV antibiotics within 30 days, or oral antibiotics within 14 days, prior to Baseline.
• History of active tuberculosis or listeriosis, or other infections suggestive of significant or profound immunosuppression, such as Pneumocystis carinii, aspergillosis or other systemic protozoal or fungal infections.
• Has latent TB (positive purified protein derivative (PPD) skin test, two-step PPD when applicable, and chest X-ray indicative of TB) or has other risk factors for the activation of latent TB, e.g. previous exposure to TB, and has not initiated TB prophylaxis prior to the first adalimumab treatment.
• Will be excluded if the Chest x-ray is found to have changes indicative of old healed tuberculous lesion (e.g. calcified nodule, fibrotic scar, apical or basilar pleural thickening etc.).

Sponsors & Collaborators

• CARE ARTHRITIS LTD.: lead
• AbbVie: collaborator

Study Sites (7)

Division of Rheumatology, University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Western University

London, Ontario, N6A 4V2, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 7W9, Canada

Location

A.M.I.R.

Montreal, Quebec, H4A 3T2, Canada

Location

GRMO Inc.

Québec, Quebec, G1B3M7, Canada

Location

CHUS Hotel-Dieu

Sherbrooke, Quebec, J1H 2E8, Canada

Location

Polmed Research Inc.

Saskatoon, Saskatchewan, S7K 0H6, Canada

Location

Related Publications (1)

• 1. National Advisory Council on Aging and Public Health Agency of Canada, Division of Aging and Seniors. Musculoskeletal disorders such as arthritis and osteoporosis [Online]. Available at http://www.naca-ccnta.ca/vignette/vig69_e.htm#69. 2. Malemud CJ. Cytokines as therapeutic targets for osteoarthritis, BioDrugs 2004;18:23- 35. 3. Abramson SB, Yazici Y. Biologics in development for rheumatoid arthritis: Relevance to osteoarthritis. 4. Pelletier JP, Martel-Pelletier J, Abramson SB.Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001;44:1237-1247. 5. Felson DT, McLaughlin S, Goggins J, LaValley MP, Gale ME, Totterman S, Li W, Hill C, Gale D: Bone marrow edema and its relation to progression of knee osteoarthritis. Ann Intern Med 2003, 139:330-336. 6. Hunter DJ, Zhang Y, Niu J, Goggins J, Amin S, LaValley MP, Guermazi A, Genant H, Gale D, Felson DT: Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis. Arthritis Rheum 2006, 54:1529-1535. 7. Kornaat PR, Kloppenburg M, Sharma R, Botha-Scheepers SA, Le Graverand MP, Coene LN, Bloem JL, Watt I: Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features. Eur Radiol 2007, 17:3073-3078. More references available

  BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dr. Walter P Maksymowych, MD, FRCPC

  CARE ARTHRITIS LTD.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 24, 2015
• First Posted: June 15, 2015
• Study Start: March 1, 2015
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: October 27, 2021

Record last verified: 2021-10

Locations

CA (7)