Clinical trial NCT03245008: Efficacy and Safety of MT-5547 in Patients With Osteoarthritis Accompanied by Moderate to Severe Pain
Official title: A Phase 2/3 (Placebo-Controlled, Double-Blind, Comparative) Study on MT-5547 in Patients With Osteoarthritis Accompanied by Moderate to Severe Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Osteoarthritis, Knee / Osteoarthritis, Hip
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2017-08-10
Enrollment: 626
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to verify the superiority of 16 weeks of MT-5547 treatment to placebo, as evidenced by the WOMAC pain score (the efficacy outcome measure), in patients with osteoarthritis of the knee or hip. Additional objectives of the study are to investigate the efficacy, safety, and pharmacokinetics of MT-5547 in long-term use.

Detailed description: The blind will be maintained, including for the study sponsor, until the key code is opened after the data have been fixed for all subjects in Week 24. In addition, in order to eliminate any bias that could affect the study assessments, to the extent possible, the blind will be maintained with respect to the study site and the subject even after the opening of the study sponsor key code.

Eligibility criteria: Inclusion Criteria:

Additional screening criteria check may apply for qualification:

* Male and female Japanese patients, 40 years to 85 years at the time written informed consent is obtained.
* Patients who have been diagnosed with osteoarthritis (OA) of the knee or hip based on the American College of Rheumatology (ACR) criteria.
* Patients with an evaluated joint (knee or hip) with a K-L (Kellgren-Lawrence) score of ≥2 based on the X-ray test performed.
* Moderate to severe pain in the evaluated joint, defined as a WOMAC pain score of ≥4 (mean of the 5 items), on the WOMAC assessments.
* Patients who satisfy both 1) and 2) below.

  1. Inadequate OA pain relief from at least 1 oral NSAID.
  2. Intolerance to or inadequate OA pain relief from at least 1 opioid (including combination drugs), or unwillingness to take opioid therapy.
* Patients who agree to not change their current lifestyle (daily living activities and exercise) throughout the study.
* Patients who are able to complete post-operative follow-up for any joint replacement surgery that is performed during the study.
* Body mass index at screening ≤39.
* Patient who are able to understand and answer endpoint questions used in the study.

Exclusion Criteria:

Additional screening criteria check may apply for qualification:

* Presence of symptoms of carpal tunnel syndrome within 6 months before screening.
* Patients who cannot undergo MRI.
* Trauma to the index joint within 3 months prior to screening.
* Presence or history of inflammatory joint diseases other than OA, Paget's disease of the spine, pelvis or femur, multiple sclerosis, fibromyalgia, vertebral tumors or infections, or renal osteodystrophy.
* Presence or history, confirmed by imaging, of arthropathy, neuropathic joint arthropathy, hip dislocation, knee dislocation, extensive subchondral cyst, marked bone destruction or bone loss, or pathologic fractures.
* Autonomic neuropathy diagnosed in the assessment of autonomic nerve symptoms performed at screening, or baseline.
* Presence or history of orthostatic hypotension at the orthostatic hypotension assessments performed at screening, prerandomization, or baseline.
* Presence or history of autonomic neuropathy, diabetic neuropathy, or other peripheral neuropathy such as reflex sympathetic dystrophy at screening.
* Presence or history of chronic familial dysautonomia.
* Intolerance to naproxen.
* Systemic (excluding topical, intranasal, ophthalmic, and inhaled formulations) corticosteroids within 4 weeks prior to screening.
* Intra-articular corticosteroids in the evaluated joint within 12 weeks prior to screening, or in any other joint within 4 weeks prior to screening.
* Received an intra-articular injection of hyaluronic acid in any joint within the period specified for each medicine prior to screening.
* Resting heart rate of \<50 bpm or \>100 bpm at screening, or baseline.
* Presence or history of 2nd or 3rd degree heart block, 1st degree heart block with abnormal QRS, or bifascicular block by ECG assessment at screening.
* Non-compliance with the Numerical rating scale (NRS) recording (average pain on walking in the evaluated joint over 1 day) during the pre-treatment observation period.
* Women who are pregnant, breast-feeding, or may be pregnant.
* Use of an anti-Nerve growth factor (anti-NGF) antibody in the past, or apparent hypersensitivity or intolerance to anti-NGF antibodies.

Primary outcomes:
measure: WOMAC Pain Score (Change From Baseline at Week 16)
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: WOMAC Physical Function Score (Change From Baseline at Week 16)
timeFrame: Baseline to Week 16
measure: WOMAC Pain Score (Change From Baseline at Each Assessment Time Point)
timeFrame: Baseline to Week 68
measure: WOMAC Physical Function Score (Change From Baseline at Each Assessment Time Point)
timeFrame: Baseline to Week 68
measure: WOMAC Stiffness Score (Change From Baseline at Each Assessment Time Point)
timeFrame: Baseline to Week 68
measure: WOMAC Total Score (Change From Baseline at Each Assessment Time Point)
timeFrame: Baseline to Week 68
measure: Patient Global Assessment (PGA) (Change From Baseline at Each Assessment Time Point)
timeFrame: Baseline to Week 68
measure: Number of Participants With Adverse Events and Adverse Drug Reactions
timeFrame: Baseline to Week 68 (Treatment period=48 weeks, Post-treatment Observation Period=20weeks)
measure: Number of Participants With a Joint Replacement Procedure is Scheduled
timeFrame: Baseline to Week 68
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Investigational Site
city: Aomori
country: Japan
facility: Investigational Site
city: Chiba
country: Japan
facility: Investigational Site
city: Ehime
country: Japan
facility: Investigational Site
city: Fukui
country: Japan
facility: Investigational Site
city: Fukuoka
country: Japan
facility: Investigational Site
city: Fukushima
country: Japan
facility: Investigational Site
city: Gunma
country: Japan
facility: Investigational Site
city: Hiroshima
country: Japan
facility: Investigational Site
city: Hokkaido
country: Japan
facility: Investigational Site
city: Hyogo
country: Japan
facility: Investigational Site
city: Ibaraki
country: Japan
facility: Investigational Site
city: Kagoshima
country: Japan
facility: Investigational Site
city: Kanagawa
country: Japan
facility: Investigational Site
city: Kumamoto
country: Japan
facility: Investigational Site
city: Kyoto
country: Japan
facility: Investigational Site
city: Mie
country: Japan
facility: Investigational Site
city: Miyagi
country: Japan
facility: Investigational Site
city: Miyazaki
country: Japan
facility: Investigational Site
city: Oita
country: Japan
facility: Investigational Site
city: Osaka
country: Japan
facility: Investigational Site
city: Saitama
country: Japan
facility: Investigational Site
city: Shiga
country: Japan
facility: Investigational Site
city: Shizuoka
country: Japan
facility: Investigational Site
city: Tokyo
country: Japan
facility: Investigational Site
city: Yamagata
country: Japan
facility: Investigational Site
city: Yamaguchi
country: Japan
facility: Investigational Site
Study officials:
affiliation: Mitsubishi Tanabe Pharma Corporation
name: General Manager
role: STUDY_DIRECTOR
References: