BOTOX® Efficacy and Safety in the Treatment of Knee Osteoarthritis

Phase 1

Conditions: Knee Osteoarthritis
MedDRA version: 17.1Level: LLTClassification code 10031165Term: Osteoarthritis kneeSystem Organ Class: 100000004859
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2014-001076-58-DK

Lead Sponsor: Allergan Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 160

Inclusion Criteria

1. Male or female, 40 to 75 years of age on the day of randomization (day 1).
2. Written informed consent has been obtained.
3. Written documentation has been obtained prior to initiating any study specific procedures in accordance with the relevant country and local privacy requirements, where applicable (e.g. Written Authorization for Use and Release of Health and Research Study Information (US sites) and written Data Protection consent (EU sites).
4. Diagnosis of primary idiopathic OA in the study knee in accordance with the American College of Rheumatology (ACR) modified clinical classification criteria for = 52 weeks prior to visit 1.
5. Kellgren-Lawrence grade II or III as confirmed by x-ray obtained at visit 1 or = 12 weeks prior to visit 1.
6. Washout of all prohibited acute and chronic pain medications (eg, anti-inflammatory drugs and analgesics) other than protocol permitted rescue treatment or other medications/treatments allowed per protocol is
completed at least 2 days prior to visit 2.
7. The average daily pain score over the first 7 days after initiation of the baseline period must be 4.0 to 9.0. This score is specific for the study knee as derived from daily pain scores recorded by the subject in the e-diary.
8. No evidence of abnormal mechanical symptoms such as locking or catching of the study knee per medical history or physical examination.
9. If a subject has bilateral knee OA, the subject must be able to distinguish which knee is the predominant source of pain. This knee must be designated as the study knee.
10. Body weight = 60 kg and = 150 kg inclusive.
11. For females of childbearing potential, a negative urine pregnancy test at visits 1, 2, and 3 (prior to the administration of the study medication) is required.
12. Must be ambulatory without assistive walking devices, able to perform usual daily activities, and agree to maintain the similar activity level throughout the course of the study.
13. Subject’s global assessment of knee OA is ‘fair’, ‘poor’, or ‘very poor’ at visit 2.
14. Ability to follow study instructions, likely to comply with the daily e-diary recording, and likely to complete all required visits.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1. Concurrent chronic pain conditions, or peripheral or central neuropathy that may affect sensation of the study knee area, including but not limited to back pain, hip pain, disc herniation, peripheral nerve entrapment, diabetic neuropathy, post-stroke pain, or fibromyalgia.
2. painDETECT Questionnaire score = 13 at visit 2.
3. Subject diagnosed with any condition suggestive of a secondary cause of knee OA including but not limited to knee trauma, articular fracture, major dysplasias or congenital abnormality, acromegaly, ochronosis, hemochromatosis, Wilson’s disease, or primary osteochondromatosis.
4. History of or current evidence of rheumatoid arthritis as diagnosed by American College of Rheumatology (ACR) criteria.
5. Presence of bursitis, or tear of meniscus or ligament of the study knee, or history of significant injury or surgery to the study knee = 52 weeks prior to visit 1.
6. Surgery of the study knee, such as, arthroplasty, arthroscopy inspection, or repair of knee ligaments that is planned to occur during the study period.
7. Treatment with IA hyaluronic acid in the study knee = 24 weeks prior to visit 1.
8. Treatment with IA corticosteroid in the study knee = 12 weeks prior to visit 1.
9. History or current diagnosis of gout or pseudogout with any joint involvement.
10. History or current diagnosis of Reiter’s, Sjögren’s syndrome, psoriasis or systemic lupus erythematosus or other autoimmune diseases with any joint involvement.
11. Evidence of skin infection or joint infection of the study knee.
12. Evidence of abnormal coagulation status (eg, excessive tooth bleeding with brushing) or subjects with hemophilia or other blood diseases affecting coagulation (eg, aplastic anemia, leukemia), or under chemo-/radio-therapy.
13. Use of prohibited medications or treatments for at least 2 days prior to initiating the baseline period or during the baseline period (which starts at visit 2 and ends at day -1)
14. Subject has initiated or changed their established physiotherapy or occupational therapy program that is specific to the lower extremities = 14 days prior to visit 3.
15. Subjects using concomitant transcutaneous electrical nerve stimulation (TENS) or acupuncture to either lower extremity = 14 days prior to visit 3.
16. Subject does not record a minimum of 5 days’ worth of e-diary data for the first 7 days after initiation of the baseline period at visit 2.
17. History of severe, progressive, or current unstable medical conditions other than OA.
18. Subjects with an active malignancy of any type or a history of malignancy = 5 years prior to visit 1, except for basal cell carcinoma of the skin that has been excised = 12 weeks prior to visit 1.
19. History of substance abuse or dependence = 52 weeks prior to visit 1, excluding nicotine and caffeine.
20. Subjects with moderately severe or severe depression as indicated by Patient Health Questionnaire-9 total score of = 15 or a score of > 0 on item # 9 at visit 1.
21. Subjects with severe anxiety as indicated by Generalized Anxiety Disorder score of = 15 at visit 1.
22. Subjects with clinically relevant level of catastrophizing defined as Pain Catastrophizing Scale score of = 30 at visit 1.
23. Known allergy or sensitivity to the study medication or its components.
24. Females who are pregnant, nursing, or planning a pregnancy during the study period.
25. Females of childbearing potential, not using a reliable means of contraception
26. Current enrol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and safety of a single IA injection of 400 U or 200 U BOTOX compared with placebo as treatment for knee OA symptoms;Secondary Objective: To explore the efficacy of a single IA injection of BOTOX (400 U or 200 U) compared with placebo on knee synovial effusion neurotransmitter/biomarker concentration profiles.;Primary end point(s): Change from baseline of the 7-day average of the daily pain score;Timepoint(s) of evaluation of this end point: Week 8

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • WOMAC pain score<br>• WOMAC physical function score<br>• GIC<br>• Daily worst pain score for the study knee;Timepoint(s) of evaluation of this end point: The secondary efficacy WOMAC and GIC variables will be summarized for each visit week at which the variable is to be recorded.

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