A Study to Evaluate the Efficacy and Safety of X0002 Spray in Subjects With Osteoarthritis of the Lumbar Spine

Inclusion Criteria:

1. Must be able to read and to provide written, personally signed, and dated informedconsent to participate in the study, in accordance with the ICH GCP Guideline E6 andapplicable regulations, before completing any study related procedures.
2. Has an understanding, ability, and willingness to fully comply with study proceduresand restrictions, as determined by the investigator.
3. Must be a male or female between 35 and 85 years of age, inclusive.
4. Must have a body mass index between 18.5 and 40.0 kg/m2, inclusive.
5. Must have a history (documented diagnosis) of clinically symptomatic OA of the lumbarspine for ≥3 months at Screening.
6. Must have a Lane Radiographic Grading Scale summary score for lumbar spine OA (levelsL1 through L5) of 1 or 2 as determined by a central radiologist at Screening.
7. Must have had low back pain while standing, walking, and/or on motion for at least 14days during the month prior to Screening per subject self-report documented by theinvestigator.
8. Must have a score ≥4 and ≤9 on a 0 to 10 (11 point) NPRS (without analgesic medicationother than rescue medication provided by the Sponsor) over the previous 7 days priorto Baseline (Day 1).
9. Must have an ODI score ≥40% and ≤90 % at Screening Visit and Baseline (Day 1).
10. With the exception of OA of the lumbar spine, must be in good general health with noclinically significant findings from medical history, vital signs, physicalexamination, ECG, and routine laboratory tests that could interfere with subjectsafety, pain or functional assessments, as determined by the investigator.
11. Female subjects must either not be of childbearing potential defined as 1)postmenopausal for at least 1 year; follicle stimulating hormone [FSH] must be inpostmenopausal range for the central lab if used to confirm postmenopausal status in awoman not using estrogen replacement therapy OR 2) surgically sterile [i.e., bilateraltubal ligation, bilateral oophorectomy, or hysterectomy]) or be willing to practiceabstinence or at least 1 of the following medically acceptable methods of birthcontrol:

• Hormonal methods such as oral, implantable, injectable, vaginal ring, ortransdermal contraceptives for a minimum of 1 full cycle (based on the subject'susual menstrual cycle period) before study drug administration;
• Intrauterine device;
• Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies orcream).

Exclusion Criteria:

1. 1. Not willing to avoid unaccustomed, strenuous physical activity (e.g., starting anew weight lifting routine) for the duration of the study starting at Screening Visitand through their completion of participation in the study. Normal physical activityis allowed.
2. Has an active or pending workman's compensation claim or litigation related to backpain.
3. Has secondary OA of the low back or OA of lower limb joints that, in the opinion ofthe investigator, could interfere with pain and functional assessments related to thelow back.
4. Has a history of spinal surgery.
5. Has more than 25% improvement from Numeric Pain Rating Scale (NPRS) score at theScreening visit to the average NPRS score over the previous 7 days prior to Day 1.
6. Has had significant injury, as judged by the investigator, involving the back withinthe 6 months before Screening.
7. Has been diagnosed with or has signs and symptoms of a radiculopathy, e.g., numbnessor tingling in a dermatomal distribution of a lower limb, sciatica, as well asetiologies of low back pain other than OA.
8. Has skin lesions or wounds on or near the lumbar spine area to be treated at Screeningor on Day 1, which may influence absorption of the medication or confound safetyassessments per the investigator's opinion.
9. Has used gabapentin, pregabalin, antiepileptics, or specific antidepressants (i.e.,tricyclics, serotonin norepinephrine reuptake inhibitors, or selective serotoninreuptake inhibitors) to treat pain in the 14 days before Screening. Other uses notrelated to the pain treatment may be permitted at the medical monitor's discretionprovided they have been at a stable dose for at least 90 days.
10. Has had injections of corticosteroids, botulinum toxin, or viscosupplements (e.g.,Synvisc®) to the spine area (eg., intra articular [IA], epidural or paraspinal) withinthe 12 weeks before Screening.
11. Has had IA, intradiscal or intravenous (IV) stem cell therapy in the 6 months prior toScreening.
12. Has received concomitant non-pharmacologic treatments (e.g., physiotherapy,acupuncture) that per investigator opinion could confound efficacy assessments within 14 days of Day 1.
13. Is not willing to discontinue any NSAIDs or other analgesics (i.e., acetaminophenother than rescue medication supplied by the Sponsor, and cyclooxygenase-2 [COX-2]inhibitors), other treatments such as cannabis, and any topical therapies (e.g.,anesthetics, capsaicin) or potentially confounding concomitant nonpharmacologictreatments (e.g., physiotherapy, acupuncture) starting at Screening Visit untilcompleting participation in the study (the use of ≤325 mg acetylsalicylic acid per dayfor cardiac prophylaxis is permitted).
14. Is not willing to discontinue applying any topical preparations containing Vitamin Aacids (including all trans retinoic acid [tretinoin], 13 cis retinoic acid [isotretinoin], 9 cis retinoic acid [alitretinoin], Vitamin A [retinol], retinal, andtheir derivatives) to the low back starting at Screening Visit until completingparticipation in the study. Topical preparations containing Vitamin A acids or retinolmay be applied to areas of the skin above the shoulders or to the lower extremities.
15. Has a history of significant hypersensitivity, intolerance, or allergy to ibuprofen,any other NSAIDs, aspirin, or acetaminophen.
16. Has used an anticoagulant or antiplatelet agent (except aspirin up to 325 mg/day forcardiac prophylaxis) in the 30 days prior to Screening.
17. Has had an active gastrointestinal (GI) ulceration in the 6 months prior to Screeningor a history of GI bleeding within 5 years of Screening.
18. Has uncontrolled depression or other uncontrolled psychiatric disorder (subjects withcontrolled depression or other psychiatric disorder, if using medication, must be on astable dose of a medication other than an epileptic, tricyclic, serotoninnorepinephrine reuptake inhibitor, or selective reuptake inhibitor for ≥12 weeks priorto Screening to participate in the study).
19. Has positive results on fecal occult blood testing at Screening or on Day 1.
20. Has a documented history of chronic inflammatory disease (such as rheumatoidarthritis, ankylosing spondylitis, axial spondyloarthropathy, psoriatic arthritis,inflammatory bowel disease or gouty arthritis) or a chronic pain condition (such asfibromyalgia), or has other conditions that may affect the spine or the functional andpain assessments (e.g., diffuse idiopathic skeletal hyperostosis, spinal stenosis,osteoporosis, severe scoliosis [curvature >30 degrees], severe kyphosis or lordosis [curvature >50 degrees]).
21. Is an asthmatic requiring treatment with systemic corticosteroids in the last year.Asthmatic subjects using inhaled corticosteroids are eligible.
22. Has uncontrolled hypertension defined as systolic blood pressure >170 mmHg ordiastolic blood pressure >90 mmHg at Baseline (may be repeated 1 additional time after 5 minutes rest to verify). The investigator may, at his discretion, choose to excludesubjects with blood pressure levels lower than these if he deems it in the bestinterest of the subject.
23. Is receiving systemic chemotherapy, has an active malignancy, lymphoproliferativedisorder or blood dyscrasia of any type, or has been diagnosed with cancer within 5years before Screening. Subjects with completely excised and healed squamous or basalcell carcinoma of the skin will be allowed.
24. Has had any osteoporosis treatments (e.g., bisphosphonates, denosumab, parathyroidhormone (PTH), strontium ranelate).
25. Has any other clinically significant unstable cardiovascular, respiratory,neurological, immunological, hematological, hepatic or renal disease, or any othercondition that, in the investigator's opinion, could compromise the subject's welfare,ability to communicate with the study staff, or otherwise contraindicate studyparticipation.
26. Has an abnormal clinical central laboratory assessment at Screening for any of thefollowing:

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkalinephosphatase or lactate dehydrogenase (LDH) ≥3 × the upper limit of normal [ULN]
• Total bilirubin ≥1.5 × ULN
• Creatinine ≥1.5 × ULN
• Hemoglobin <10 g/dL

27. Has any other clinically significant central laboratory finding at Screening that inthe investigator's opinion contraindicates study participation;
28. Has clinically significant abnormality on 12-lead ECG, including a QTcF interval >450milliseconds for males and 470 msec for females.
29. Is pregnant, planning to become pregnant during the study, or lactating; for women ofchildbearing potential, serum and urine pregnancy test must be negative at ScreeningVisit and urine pregnancy test must be negative at Baseline (Day 1) for subject to beeligible to participate.
30. Has participated in a previous clinical study with X0002.
31. Has participated in any other investigational clinical trial within the past 30 daysor 5 half-lives of the investigational drug, whichever is longer, prior to Screening.
32. Has known alcohol or other substance abuse in the investigator's opinion.
33. Is a participating investigator, sub-investigator, study coordinator, or employee of aparticipating investigator, or is an immediate family member of the aforementioned.
34. Has any factor, which in the opinion of the investigator would jeopardize theevaluation or safety or be associated with poor adherence to the protocol.
35. Does not have access to telephone and/or ability to gain technology access.