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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 (FACT OA1)

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ClinicalTrials.gov Identifier: NCT03161093
Recruitment Status : Recruiting
First Posted : May 19, 2017
Last Update Posted : September 19, 2018
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 18, 2017
First Posted Date  ICMJE May 19, 2017
Last Update Posted Date September 19, 2018
Actual Study Start Date  ICMJE September 21, 2017
Estimated Primary Completion Date August 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2017)
  • Change in the WOMAC pain subscale scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with placebo [ Time Frame: Baseline to Week 16 ]
  • Change in the WOMAC physical function subscale scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with placebo [ Time Frame: Baseline to Week 16 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03161093 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • Change in the Patient Global Assessment (PGA) scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with placebo [ Time Frame: Baseline to Week 16 ]
  • Percentage of patients treated with fasinumab, compared with that of patients treated with placebo, who had a response at week 16, with response defined as an improvement by ≥30% in the WOMAC pain subscale scores [ Time Frame: Baseline to Week 16 ]
  • Change in WOMAC pain subscale scores from baseline to week 16 in patients treated with fasinumab, compared with that of patients treated with naproxen [ Time Frame: Baseline to Week 16 ]
  • Change in WOMAC physical function subscale scores from baseline to week 16 in patients treated with fasinumab, compared with that of patients treated with naproxen [ Time Frame: Baseline to Week 16 ]
  • Change in WOMAC pain subscale scores from baseline to week 52 in patients treated with fasinumab, compared with that of patients treated with placebo [ Time Frame: Baseline to Week 52 ]
  • Change in WOMAC physical function subscale scores from baseline to week 52 in patients treated with fasinumab, compared with that of patients treated with placebo [ Time Frame: Baseline to Week 52 ]
  • Change in the PGA scores from baseline to week 52 in patients treated with fasinumab compared with that of patients treated with placebo [ Time Frame: Baseline to Week 52 ]
  • Change in the PGA scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with naproxen [ Time Frame: Baseline to Week 16 ]
  • Incidence of Adjudicated Arthropathy (AA) (as confirmed by adjudication) [ Time Frame: Baseline to Week 100 ]
  • Incidence of Destructive Arthropathy (DA) (as confirmed by adjudication) [ Time Frame: Baseline to Week 100 ]
  • Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline to Week 100 ]
  • Incidence of sympathetic nervous system dysfunction [ Time Frame: Baseline to Week 100 ]
  • Incidence of Peripheral sensory AEs that require a neurology or other specialty consultation [ Time Frame: Baseline to Week 100 ]
  • Incidence of all-cause joint replacement (JR) through week 52 and through the follow-up period [ Time Frame: Baseline to Week 72 ]
  • Incidence of JRs at the telephone survey [ Time Frame: 52 weeks after last dose of study drug ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2017)
  • Change in the Patient Global Assessment (PGA) scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with placebo [ Time Frame: Baseline to Week 16 ]
  • Percentage of patients treated with fasinumab, compared with that of patients treated with placebo, who had a response at week 16, with response defined as an improvement by ≥30% in the WOMAC pain subscale scores [ Time Frame: Baseline to Week 16 ]
  • Change in WOMAC pain subscale scores from baseline to week 16 in patients treated with fasinumab, compared with that of patients treated with naproxen [ Time Frame: Baseline to Week 16 ]
  • Change in WOMAC physical function subscale scores from baseline to week 16 in patients treated with fasinumab, compared with that of patients treated with naproxen [ Time Frame: Baseline to Week 16 ]
  • Change in WOMAC pain subscale scores from baseline to week 52 in patients treated with fasinumab, compared with that of patients treated with placebo [ Time Frame: Baseline to Week 52 ]
  • Change in WOMAC physical function subscale scores from baseline to week 52 in patients treated with fasinumab, compared with that of patients treated with placebo [ Time Frame: Baseline to Week 52 ]
  • Change in the PGA scores from baseline to week 52 in patients treated with fasinumab compared with that of patients treated with placebo [ Time Frame: Baseline to Week 52 ]
  • Change in the PGA scores from baseline to week 16 in patients treated with fasinumab compared with that of patients treated with naproxen [ Time Frame: Baseline to Week 16 ]
  • Incidence of severe Adjudicated Arthropathy (AA) (as confirmed by adjudication) [ Time Frame: Baseline to Week 100 ]
  • Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline to Week 100 ]
  • Incidence of AA (as confirmed by adjudication) [ Time Frame: Baseline to Week 100 ]
  • Incidence of sympathetic nervous system dysfunction [ Time Frame: Baseline to Week 100 ]
  • Incidence of all-cause joint replacement (JR) through week 52 and through the follow-up period [ Time Frame: Baseline to Week 72 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase 3 Randomized, Double-blind, Multi-dose, Placebo and Naproxen-Controlled Study to Evaluate the Efficacy and Safety of Fasinumab in Patients With Pain Due to Osteoarthritis of the Knee or Hip
Brief 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 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 OA of the knee or hip
  2. To evaluate the efficacy of fasinumab compared with placebo, when administered for up to 52 weeks in patients with 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 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 OA of the knee or hip
  5. To evaluate the pharmacokinetic (PK) profile of fasinumab administered to patients for up to 52 weeks
  6. To evaluate the immunogenicity of fasinumab administered to patients for up to 52 weeks
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Osteoarthritis, Knee
  • Osteoarthritis, Hip
Intervention  ICMJE
  • Drug: Fasinumab
    Solution for injection in pre-filled syringe
    Other Name: REGN475
  • Drug: Naproxen
    Pharmaceutical form: Capsule
  • Drug: Fasinumab-matching placebo
    Solution for injection in pre-filled syringe
  • Drug: Naproxen-matching placebo
    Capsule
Study Arms  ICMJE
  • Experimental: Fasinumab dosing regimen 1
    Fasinumab Subcutaneous (SC) dosing regimen 1 and naproxen-matching placebo oral
    Interventions:
    • Drug: Fasinumab
    • Drug: Naproxen-matching placebo
  • Experimental: Fasinumab dosing regimen 2
    Fasinumab SC dosing regimen 2 and naproxen-matching placebo oral
    Interventions:
    • Drug: Fasinumab
    • Drug: Naproxen-matching placebo
  • Experimental: Fasinumab-matching placebo and naproxen
    Interventions:
    • Drug: Naproxen
    • Drug: Fasinumab-matching placebo
  • Experimental: Fasinumab-matching placebo and naproxen-matching placebo
    Interventions:
    • Drug: Fasinumab-matching placebo
    • Drug: Naproxen-matching placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 17, 2018)
2845
Original Estimated Enrollment  ICMJE
 (submitted: May 18, 2017)
3640
Estimated Study Completion Date  ICMJE April 5, 2021
Estimated Primary Completion Date August 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria include, but are not limited to, the following:

  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

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com
Listed Location Countries  ICMJE Denmark,   Hungary,   Lithuania,   Poland,   Romania,   Russian Federation,   South Africa,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03161093
Other Study ID Numbers  ICMJE R475-OA-1611
2016-005020-29 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Regeneron Pharmaceuticals
Study Sponsor  ICMJE Regeneron Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP