Clinical trial NCT02067611: A Study to Evaluate the Efficacy and Safety of X0002 Spray in Subjects With Osteoarthritis
Official title: A Phase 2, Multicenter, Randomized, Double Blind, Placebo Controlled, Parallel Group, Dose Range Finding Study to Evaluate the Efficacy and Safety of X0002 Spray Versus Placebo in Subjects With Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis of the Knee
Keywords: Phase 2, Efficacy, Safety, Osteoarthritis
Lead sponsor: Techfields Pharma Co. Ltd
Sponsor class: INDUSTRY
First posted: 2014-02-20
Enrollment: 216
Sex: ALL
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 2, multicenter, randomized, double blind (with dose), placebo controlled, parallel group, proof of concept, and dose range finding study to evaluate the efficacy, safety, and PK of X0002 spray in adult subjects with clinically symptomatic mild to moderate OA of the knee.

Objectives of the study:

1. To evaluate the efficacy of X0002 spray compared to placebo for relief of knee pain in subjects with osteoarthritis (OA) of the knee;
2. To assess the safety and tolerability of multiple doses of X0002 when administered as a topical spray.

Detailed description: This is a phase 2, multicenter, randomized, double blind (with dose), placebo controlled, parallel group, proof of concept, and dose range finding study to evaluate the efficacy, safety, and PK of X0002 spray in adult subjects with clinically symptomatic mild to moderate OA of the knee.

After a screening period of up to 3 weeks and radiographic evaluation of the target knee joint space, 225 subjects will be randomly assigned to 1 of 3 treatment groups in a 1:1:1 ratio with a 2:1 ratio of active:placebo within each treatment group in a 1:1:1 ratio with a 2:1 ratio of active:placebo within each treatment group (i.e., 2 subjects to active treatment and 1 subject to placebo):

Group A: low dose of X0002, twice daily (BID, approximately every 12 hours; n=50) or placebo (low dose), BID (approximately every 12 hours; n=25); Group B: middle dose of X0002, BID (approximately every 12 hours; n=50) or placebo , BID (approximately every 12 hours; n=25) ; Group C: High dose of X0002, BID (approximately every 12 hours; n=50) or placebo, BID (approximately every 12 hours; n=25) .

Safety and efficacy assessments will be performed at at 2, 4, 8, and 12 weeks of treatment.

Eligibility criteria: Inclusion Criteria:

* A subject must be a male or female between 35 and 85 years of age, inclusive.
* A subject must have a body mass index (BMI) between 18.5 and 39.9 kg/m2, inclusive.
* A subject must have a diagnosis of idiopathic OA according to the American College of Rheumatology (ACR) clinical and radiographic criteria (knee pain, osteophytes, and at least one of the following: \>50 years of age, morning stiffness lasting \<30 minutes after getting up in the morning, or crepitus).
* A subject must have a Kellgren Lawrence Grade of 1 or 2 as determined by the Investigator or a local radiologist at Screening.
* A subject must have a history of clinically symptomatic mild to moderate OA of the knee for ≥6 months.
* A subject must have had knee pain while standing, walking, and/or on motion for at least 14 days during the month prior to Screening.
* A subject must have a knee pain score ≥40 mm and \<90 mm on a 100 mm VAS (with or without analgesic medication) on at least 10 of the 14 days prior to randomization.
* A subject must be willing to discontinue any NSAIDs or other analgesic (eg, aspirin, acetaminophen) or potentially confounding concomitant treatments (eg, physiotherapy, acupuncture) starting 4 days before the administration of the first dose of study medication until completing participation in the study. (The use of ≤325 mg acetylsalicylic acid per day as cardiac prophylaxis is permitted.) The subject will be allowed to take rescue medication (acetaminophen) for pain during the study except during the 24 hours prior to Baseline (Day1), Week 2, Week 4, Week 8, Week 12/EOS, and Follow-up assessments.
* A subject must be willing to avoid unaccustomed physical activity (eg, starting a new weight lifting routine) for the duration of the study.

Exclusion Criteria:

* A subject who has secondary OA of the knee or OA of lower limb joints other than the knee that, in the opinion of the Investigator, could interfere with pain and functional assessments related to the knee
* A subject who has OA of the knee with a Kellgren Lawrence Grade ≥3 as determined by the Investigator or a local radiologist at Screening
* A subject who has a history of total or partial knee replacement, arthroplasty, or other knee surgery on either knee
* A subject who has had significant injury, as judged by the Investigator, involving the target knee within the 6 months before Screening.
* A subject who has skin lesions or wounds on or near the knees to be treated at Screening or on Day 1 prior to the first administration of study medication
* A subject who has used opiates or corticosteroids within 30 days before Screening or who requires treatment with chronic opiates or corticosteroids
* A subject who has had intra articular injections of corticosteroids, hyaluronic acid, or viscosupplements (eg, Synvisc®) to a knee to be treated within the 3 months before Screening.
* A subject who has a history of significant hypersensitivity, intolerance, or allergy to ibuprofen, any NSAIDs, aspirin, or acetaminophen
* A subject who has had an active peptic ulceration in the 12 months prior to Screening or a history of gastrointestinal (GI) bleeding within 5 years of Screening
* A subject who has used an anticoagulant (except aspirin up to 325 mg/day for cardiac prophylaxis) in the month prior to Screening
* A subject who has positive results on fecal occult blood testing at Screening or on Day 1 prior to the first administration of study medication
* A subject who has a history of chronic inflammatory disease (such as rheumatoid arthritis, psoriatic arthritis, gouty arthritis), fibromyalgia, conditions that may affect the target joint (eg, osteonecrosis, chondrocalcinosis), or asthma.

Primary outcomes:
measure: To Evaluate the Efficacy of X0002 Spray Compared to Placebo for Relief of Knee Pain in Subjects With Osteoarthritis (OA) of the Knee
timeFrame: 4 weeks of treatment
Secondary outcomes:
measure: To Assess the Safety and Tolerability of Multiple Doses of X0002 When Administered as a Topical Spray
timeFrame: 2, 8, and 12 weeks of treatment
measure: To Evaluate the Effect of X0002 Spray Compared to Placebo for the Relief of Joint Stiffness
timeFrame: 2, 4, 8, and 12 weeks of treatment
measure: To Assess the Effect of X0002 Spray Compared to Placebo on Difficulty Performing Daily Activities
timeFrame: at 2, 4, 8, and 12 weeks of treatment
measure: Characterize the Pharmacokinetics of X0002
timeFrame: at the Week 2, week 3, week 4 and Week 12
Other outcomes:
measure: Subject's Global Assessment of Disease Status of the Target Knee at 2, 4, 8 and 12 Weeks of Treatment
timeFrame: at 2, 4, 8, and 12 weeks of treatment
measure: Investigator's Global Assessment of Disease Status of the Target Knee at 2, 4, 8 and 12 Weeks of Treatment
timeFrame: at 2, 4, 8, and 12 weeks of treatment
measure: Subject's Global Assessment of Response to Therapy of the Target Knee at 2, 4, 8 and 12 Weeks of Treatment
timeFrame: at 2, 4, 8, and 12 weeks of treatment
measure: Investigator's Global Assessment of Response to Therapy of the Target Knee at 2, 4, 8 and 12 Weeks of Treatment
timeFrame: at 2, 4, 8, and 12 weeks of treatment
measure: Change From Baseline Over Time in VAS Pain Scores for the Target Knee From Daily Diary Data.
timeFrame: at 2, 4, 8, and 12 weeks of treatment
measure: Amount of Rescue Medication (Acetaminophen) Consumed Per Day for Target Knee Pain.
timeFrame: at 2, 4, 8, and 12 weeks of treatment
Locations:
city: Tempe
country: United States
facility: Fiel Family & Sports Medicine/Clinical Research Advantage Inc
state: Arizona
city: Carmichael
country: United States
facility: Med Center
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Trumbull
country: United States
facility: New England Research Assoc.
state: Connecticut
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Jupiter
country: United States
facility: Health Awareness Inc.
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Georgia
city: Prairie Village
country: United States
facility: Clinical Trials Technology(CTT) Consultants, Inc.
state: Kansas
city: Hazelwood
country: United States
facility: Healthcare Research Network
state: Missouri
city: Saint Louis
country: United States
facility: Sundance Clinical Research, LLC
state: Missouri
city: Albuquerque
country: United States
facility: New Mexico Clinical Research & Osteoporosis Center, Inc.
state: New Mexico
city: Cincinnati
country: United States
facility: Hightop Medical Research
state: Ohio
city: Franklin
country: United States
facility: Prestige Clinical Research, LLC
state: Ohio
city: Beaver
country: United States
facility: Heritage Valley Medical Group
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: San Antonio
country: United States
facility: Quality Research Inc
state: Texas
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc
state: Virginia
Study officials:
affiliation: Techfields Inc
name: Chongxi Yu, Ph.D.
role: STUDY_CHAIR
References: