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
Condition: Osteoarthritis, Knee; Osteoarthritis, Hip
MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip
Intervention: Fasinumab; Naproxen; Fasinumab-matching placebo; Naproxen-matching placebo
Intervention description: Solution for injection in pre-filled syringe; Pharmaceutical form: Capsule; Solution for injection in pre-filled syringe; Capsule
Intervention MeSH terms: Naproxen; Fasinumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 3307.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to evaluate the efficacy of fasinumab compared with
      placebo, when administered for up to 16 weeks in patients with pain due to osteoarthritis
      (OA) of the knee or hip.

      The secondary objectives of the study are:

        1. To evaluate the efficacy of fasinumab compared with naproxen, when administered for up
           to 16 weeks in patients with pain due to OA of the knee or hip

        2. To evaluate the efficacy of fasinumab compared with placebo, when administered for up to
           44 weeks in patients with pain due to OA of the knee or hip

        3. To assess the safety and tolerability of fasinumab compared with naproxen, when
           administered for up to 16 weeks in patients with pain due to OA of the knee or hip

        4. To assess the safety and tolerability of fasinumab compared with naproxen, when
           administered for up to 52 weeks in patients with pain due to OA of the knee or hip

        5. To assess the safety and tolerability of fasinumab compared with naproxen, when
           administered for up to 104 weeks in patients with pain due to OA of the knee or hip

        6. To evaluate the pharmacokinetic (PK) profile of fasinumab administered to patients with
           pain due to OA of the knee or hip for up to 52 weeks

        7. To evaluate the PK profile of fasimumab administered to patients with pain due to OA of
           the knee or hip for up to 104 weeks

        8. To evaluate the immunogenicity of fasinumab administered to patients with pain due to OA
           of the knee or hip for up to 52 weeks

        9. To evaluate the immunogenicity of fasinumab administered to patients with pain due to OA
           of the knee or hip for up to 104 weeks

       10. To evaluate the efficacy of fasinumab compared with naproxen, when administered for up
           to 44 weeks in patients with pain due to OA of the knee or hip
    

Eligibility criteria:

        Inclusion Criteria include, but are not limited to, the following:

        Year 1:

          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 (acetaminophen/paracetamol) to be taken as needed with a maximum
             daily dose of 2500 mg (countries where 500 mg strength tablets/capsules are available)
             or 2600 mg (countries where 325 mg strength tablets/capsules are available)

          5. A history of at least 12 weeks of analgesics use for pain due to OA of the knee or
             hip, as defined by:

               1. Inadequate pain relief from acetaminophen/paracetamol AND

               2. Intolerance to or inadequate pain relief from opioid or tramadol therapy,
                  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.

          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

        Year 2:

        Note: Any Year 1 patient attending their week 52 visit on or after 26 March 2020 will no
        longer have the option to enroll into Year 2.

          1. Completed the treatment period of Year 1

          2. Did not permanently discontinue study drug during Year 1

          3. Received no less than 10 of the 13 planned doses of SC study drug during the treatment
             period of Year 1

          4. Provide informed consent for Year 2

          5. Willing to continue to maintain current activity and exercise levels throughout Year 2

        Exclusion Criteria include, but are not limited to, the following:

          1. Non-compliance with the Numeric Rating Scale (NRS) recording during the
             pre-randomization period

          2. History or presence at the screening visit of non-OA inflammatory joint disease,
             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, neuropathic joint arthropathy, hip or
             knee dislocation, extensive subchondral cysts, significant bone collapse or 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

          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 needed

          8. History or presence at the screening visit of autonomic or 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

         10. History of naproxen intolerance, or existence of a medical condition that is high risk
             for naproxen-associated complications

         11. Resting heart rate of <50 beats per minute (bpm) or >100 bpm at the screening or
             randomization visits

         12. History or presence of 2nd or 3rd degree heart block, 1st degree heart block with
             abnormal Complex of Q, R, and S waves on an electrocardiogram (QRS) complex, or
             bifascicular block by ECG assessment at the screening visit

         13. History or presence of orthostatic hypotension at the screening, prerandomization, or
             randomization visits

         14. History of poorly controlled hypertension

         15. Use of systemic corticosteroid within 30 days prior to the screening visit.
             Intra-articular corticosteroids in the index joint within 12 weeks prior to the
             screening visit, or to any other joint within 30 days prior to the screening visit

         16. Exposure to an anti-Nerve growth factor (NGF) antibody prior to the screening visit or
             known sensitivity or intolerance to anti-NGF antibodies