A study to determine the safety and the efficacy of fasinumab compared to placebo and naproxen for treatment of adults with pain from osteoarthritis of the knee or hip

Phase 1

• Conditions: Pain due to osteoarthritis of the knee or hip; MedDRA version: 20.0Level: LLTClassification code 10023476Term: Knee osteoarthritisSystem Organ Class: 100000004859; MedDRA version: 20.0Level: LLTClassification code 10020108Term: Hips osteoarthritisSystem Organ Class: 100000004859; Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

• Registration Number: EUCTR2016-005020-29-ES
• Lead Sponsor: Regeneron Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-12-01
• Last Update Posted: 26 February 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 3640

Inclusion Criteria

A patient must meet the following criteria to be eligible for inclusion in the study:
1. Male and female patients, at least 18 years of age, at screening
2. A clinical diagnosis of OA of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score =2 for the index joint) at the screening visit
3. Moderate to severe pain in the index joint defined at both the screening and randomization visits
4. Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments (paracetamol/acetaminophen to be taken as needed with a maximum daily dose of 2500 mg in Europe and 2600 mg in countries outside of Europe)
5. A history of at least 12 weeks of inadequate pain relief or intolerance to analgesics used for pain due to OA of the knee or hip, as defined by
a. Inadequate pain relief from acetaminophen/paracetamol AND
b. Intolerance to or inadequate pain relief from at least 1 opioid or tramadol, unwillingness to take opioid or tramadol therapy for a medically acceptable reason, or lack of access to an opioid or to tramadol
6. Currently using a stable dose of NSAID, defined as using NSAIDs for approximately 4 days per week over the last 4 weeks.
7. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the initial 16 weeks of treatment
8. Stable treatment with glucosamine sulfate and chondroitin sulfate treatments must be stopped during the pre-randomization period
9. Consent to allow all radiographs and medical/surgical/hospitalization records of care received elsewhere prior to and during the study period to be shared with the investigator
10. Willing to maintain current activity and exercise levels throughout the study
11. Willing and able to comply with clinic visits and study-related procedures and willing to provide follow-up information related to any JR surgery that occurs within the period of time covered by their intended participation in the study
12. Able to understand and complete study-related questionnaires
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 2000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1640

Exclusion Criteria

A patient who meets any of the following criteria will be excluded from the study:
1. Non-compliance with the NRS recording during the pre-randomization period (4 or more consecutive missed diary entries)
2. History or presence at the screening visit of non-OA inflammatory joint disease (eg, rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, pseudo-out, gout, spondyloarthropathy, joint infections within the past 5 years), Paget's disease of the spine, pelvis or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy
3. History or presence on imaging of arthropathy (osteonecrosis, subchondral insufficiency fracture, rapidly progressive OA type 1 or type 2), neuropathic joint arthropathy, hip dislocation (prosthetic hip dislocation is eligible), knee dislocation (patella dislocation is eligible), extensive subchondral cysts, significant bone collapse, significant bone loss, or pathologic fractures
4. Trauma to the index joint within 3 months prior to the screening visit
5. Signs or symptoms of carpal tunnel syndrome within 6 months of screening visit
6. Patient is not a candidate for MRI
7. Is scheduled for a JR surgery to be performed during the study period or who would be unwilling or unable to undergo JR surgery if one eventually became necessary
8. History or presence at the screening visit of autonomic neuropathy,diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy
9. History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy (Shy-Drager syndrome)
10. History of naproxen intolerance, or existence of a medical condition (eg, high risk of GI bleed, previous ulcer, use of anti-coagulants, or the use of concomitant medication for which naproxen is contraindicated
11. Known allergy or sensitivity to doxycycline or related compounds, or monoclonal antibodies
12. Poorly controlled diabetes (defined as any single value of hemoglobin A1c [HbA1c]>9.0%) at the screening visit
13. Known history of human immunodeficiency virus infection
14. Known history of ocular herpes simplex virus, herpes simplex virus pneumonia, or herpes simplex virus encephalitis
15. History of sickle cell disease, including sickle cell anemia and ß- thalassemia
16. Confirmed elevated screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =2.5 times the upper limit of normal (ULN)
17. Resting heart rate of <50 beats per minute (bpm) or >100 bpm (by vital sign assessment or as captured during electrocardiogram [ECG] assessment) at the screening or randomization visits
18. History or presence of 2nd or 3rd degree heart block, 1st degree heart block with abnormal QRS complex, or bifascicular block by ECG assessment at the screening visit
19. History or presence of orthostatic hypotension, as defined in Section 8.2.3.4, at the screening, pre-randomization, or randomization visits
20. History of poorly controlled hypertension, as defined by:
a. Systolic blood pressure =180 mm Hg or diastolic blood pressure =110 mm Hg at the screening visit
b. Systolic blood pressure of 160 mm Hg to 179 mm Hg or diastolic blood pressure
of 100 mm Hg to 109 mm Hg at the screening visit, AND a history of endorgan damage (including history of left ventricular hypertrophy, heart failure, angina, myocardial infraction, stroke, transient ischemic attack, peripheral arterial disease and moderate to

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified