A Study to Evaluate the Efficacy and Safety of X0002 Spray in Subjects With Osteoarthritis
Condition: Osteoarthritis of the Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: X0002; Placebo
Intervention description: Parallel Assignment; Parallel Assignment
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 216.0
Sex: All
Minimum age: 35 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Phase 2, Efficacy, Safety, Osteoarthritis

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.
    

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.