Inclusion Criteria:
1. Ability to read and provide written, personally signed, and dated informed consent to
participate in the study, in accordance with the ICH GCP Guideline E6 and applicable
regulations, before completing any study related procedures.
2. An understanding, ability, and willingness to fully comply with study procedures and
restrictions.
3. Subject must be a male or female between 35 and 85 years of age, inclusive.
4. Female subjects must either not be of childbearing potential (defined as
postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation,
bilateral oophorectomy, or hysterectomy]) or be willing to Practice at least 1 of the
following medically acceptable methods of birth control.
5. Subject must have a body mass index (BMI) between 18.5 and 45 kg/m2, inclusive.
6. Must have a history of clinically symptomatic OA of the knee for ≥6 months.
7. Must meet the American College of Rheumatology clinical classification criteria for
knee OA. These criteria include the presence of knee pain in addition to at least 3 of
the following 6 items:
- - stiffness lasting <30 minutes.
- - crepitus on knee motion.
8. A subject must have a Kellgren Lawrence Grade of 2,3 or 4 as determined by a central
radiologist at the first screening visit. .
9. Subject must have had knee pain while standing, walking, and/or in motion for at least
14 days during the month prior to Screening.
10. Subject must have a knee pain score ≥4 and <9 on 0-10 pain intensity NRS (without
analgesic medication) on at least 7 of the 10 days prior to randomization.
11. Subject must be willing to discontinue any NSAIDs or other analgesic (eg, aspirin,
acetaminophen) or potentially confounding concomitant treatments (eg, physiotherapy,
acupuncture) starting on the first screening visit 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 the Second Screening Visit,
Baseline (Day1), Week 2, Week 4, Week 8, Week 12, Week 22, Week 32, Week 42, and Week
52/EOS.
12. Subject must be willing to discontinue applying any topical preparations containing
Vitamin A acids (including all trans retinoic acid (tretinoin), 13 cis retinoic acid
[isotretinoin], 9 cis retinoic acid [alitretinoin], vitamin A [retinol], retinal, and
their derivatives) to the lower limbs starting on the first screening visit until
completing participation in the study. (Topical preparations containing Vitamin A
acids or retinol may be applied to areas of the skin above the waist, but should not
be applied to areas of the skin exposed to study medication.)
13. Subject must be willing to avoid unaccustomed physical activity (eg, starting a new
weight lifting routine) for the duration of the study starting on the first screening
visit.
14. With the exception of OA of the knee subjects with medical history must be stable as
determined by the investigator.
Exclusion Criteria:
1. Has worker's compensation injuries affecting the knee or back.
2. Has a history of or is currently in litigation regarding joint injuries.
3. Has secondary OA of the target knee or OA of lower limb joints other than the knee
that, in the investigator's opinion, could interfere with pain and functional
assessments related to the target knee.
4. Has a history of total or partial knee replacement, arthroplasty, or other knee
surgery on the target knee.
5. In the investigator's opinion, has had significant injury involving the target knee
within the 6 months before Screening.
6. Has skin lesions or wounds on or near the target knee at Screening or at Baseline (Day
1) that, in the investigator's opinion, would affect absorption of the medication.
7. Has used opiates (including tramadol or tapentadol) or systemic corticosteroids within
30 days before Screening or requires treatment with chronic opiates or systemic
corticosteroids.
8. Subjects with a placebo response exceeding 25% improvement in the average Western
Ontario and McMaster Osteoarthritis Index [WOMAC] pain subscale score from Screening
Visit to Day 1 will be excluded.
9. Has used gabapentin, pregabalin, antiepileptics, or specific antidepressants (i.e.,
tricyclics, serotonin norepinephrine reuptake inhibitors, or selective serotonin
reuptake inhibitors) to treat pain in the 14 days before Screening. Other uses not
related to the pain treatment may be permitted at the medical monitor's discretion
provided they have been at a stable dose for at least 90 days.
10. Has had intra articular (IA) injections of corticosteroids, hyaluronic acid, or
viscosupplements (e.g., Synvisc®) to the target knee within the 12 weeks before
Screening. 11. Has had IA or intravenous (IV) stem cell therapy in the 6 months prior to Screening. 12. Is receiving or is planning to receive concomitant nonpharmacologic treatments (e.g.,
physiotherapy, acupuncture) that in the investigator's opinion could confound efficacy
assessments within 14 days of Day 1.
13. Has a history of significant hypersensitivity, intolerance, or allergy to ibuprofen or
any other NSAIDs, aspirin, or acetaminophen.
14. Has had an active gastrointestinal (GI) ulceration in the 6 months prior to Screening
or a history of GI bleeding within 5 years of Screening.
15. Has used an anticoagulant or antiplatelet agent (except aspirin up to 325 mg/day for
cardiac prophylaxis) in the 30 days prior to Screening.
16. Has a documented history of chronic inflammatory disease (e.g., rheumatoid arthritis,
psoriatic arthritis, inflammatory bowel disease, gouty arthritis) OR chronic pain
condition (e.g., fibromyalgia), OR has other conditions that may affect the target
joint for the functional and pain assessments (e.g., osteonecrosis,
chondrocalcinosis).
17. Has uncontrolled depression or other uncontrolled psychiatric disorder (subjects with
controlled depression or other psychiatric disorder, if using medication, must be on a
stable dose of a medication other than an epileptic, tricyclic, serotonin
norepinephrine reuptake inhibitor, or selective reuptake inhibitor for ≥12 weeks prior
to Screening to participate in the study).
18. Has asthma requiring treatment with systemic corticosteroids in the last year prior to
Screening. Asthmatic subjects using inhaled corticosteroids are eligible.
19. Has uncontrolled hypertension defined as systolic blood pressure >170 mmHg and
diastolic blood pressure >90 mmHg at the Screening or Baseline Visit (may be repeated
after 5 minutes rest to verify).
20. Is receiving systemic chemotherapy, has an active malignancy, lymphoproliferative
disorder, or blood dyscrasia of any type, or has been diagnosed with cancer within 5
years before Screening. Subjects with completely excised squamous or basal cell
carcinoma of the skin will be allowed.
21. Has any clinically significant unstable cardiac, respiratory, neurological,
immunological, hematological, hepatic, or renal disease, or any other condition that,
in the Investigator's opinion, could confound the study results, compromise the
subject's welfare, interfere with the ability to communicate with the study staff, or
otherwise contraindicate study participation.
22. Has any of the following conditions at Screening:
- - Stage 4 or 5 end-stage renal disease.
23. Subject has any other clinically significant laboratory finding at Screening that in
the investigator's opinion contraindicates study participation.
24. Has clinically significant abnormality at Screening or Baseline (Day 1) on 12-lead
ECG, including a QT interval calculated using Fridericia's correction (QTcF) interval
>500 milliseconds (msec) or evidence of cardiac ischemia (i.e., Evident q waves: t
wave inversion).
25. Is pregnant, planning to become pregnant during the study, or lactating. Has a
positive serum and urine pregnancy test at Screening Visit, or a positive urine
pregnancy test at Baseline (Day 1).
26. Has a positive urine drug screen for a nonprescribed drug prohibited by the protocol
at Screening.
27. Has known alcohol or other substance abuse in the investigator's opinion.
28. Has participated in a previous clinical study with X0002.
29. Has participated in any other clinical trial within the past 30 days or within 5
half-lives of the study drug prior to Screening, whichever is longer.
30. Is a participating investigator, sub-investigator, study coordinator, or employee of a
participating investigator, or is an immediate family member of the aforementioned.
31. Has any factor that, in the investigator's opinion, would jeopardize the evaluation or
safety or be associated with poor adherence to the protocol.
32. Is without access to telephone and/or ability to gain technology access.
