Inclusion Criteria.Volunteers will be included in the study only if they satisfy all the following criteria:
1. Able to read, understand, sign, and date the subject informed consent.
2. Have given written informed consent before any study-related activities are carried
out and are able to understand the nature and purpose of the trial, including
possible risks and adverse effects.
3. Adult males and females, 50 to 80 years of age (inclusive) at Screening.
4. Body weight less than 136 kgs (300 lbs) at Screening.
5. Except for OA, subject is medically healthy (in the opinion of the PI), as
determined by prestudy medical history, and without clinically significant
abnormalities including:
1. Clinically relevant findings on physical examination that would preclude trial
compliance.
2. Heart rate <40 BPM or >100 BPM after 5 minutes rest in supine or semi-supine
position.
3. Body temperature <95.9°F or >99.8°F. Note: The above assessments may be
repeated, if abnormal values are recorded in the first instance, at the
discretion of the Investigator (or delegate).
6. Available X-Ray of target knee obtained within 12 months prior to Screening with
radiographic evidence of osteoarthritis in the medial and/or lateral tibio-femoral
compartment; KL grading is not required.
7. Clinical diagnosis of knee OA with at least 2 of the 4 following signs/symptoms in
the target knee, and in the absence of palpable warmth suggesting synovitis or
infection:
- - Crepitus on knee extension.
- - Morning stiffness in target knee <30 minutes.
8. Stability of Cruciate and collateral ligaments as defined by clinical examination
(e.g. tests such as Lachman, pivot shift, posterior drawer, posterior sag, valgus
and Varus stress).
9. Results of the KOOS Knee Survey Screening Questionnaire performed at Screening for
the target knee that indicate either: moderate or greater difficulty in at least 5
of 17 questions (A1-17) in the "Function, daily living" subsection; or a total score
of at least 20/68 in that subsection.
10. Results of the KOOS Knee Survey Screening Questionnaire performed at Screening that
indicate moderate or greater pain on question P6 "pain going up or down stairs" in
the target knee.
11. Willing to use only acetaminophen (Tylenol® or equivalent), hydrocodone,
orhydrocodone/acetaminophen (e.g., Norco® or equivalent) for breakthrough pain
during the4-week injection period. The maximum dose of acetaminophen from all
sources must not exceed 4000 mg/day.
12. Willing NOT to use non-steroidal anti-inflammatory drugs such as aspirin, ibuprofen
(Motrin® or equivalent), or naproxen (Aleve® or equivalent) during the 4-week
injection period.
13. Willing NOT to use approved or investigational IA products for knee OA for the
duration of participation in the study.
14. If using GLP-1 medications such as Wegovy® or similar, must be on a stable dose for
at least 2 months prior to Screening.
15. Female subjects of childbearing potential who are sexually active (non-abstinent)
must agree to and comply with using 2 highly effective methods of birth control
(oral contraceptive implant, injectable or indwelling intrauterine device, condom
with spermicide or sexual abstinence) while participating in the study. Male
participants must agree to use a barrier contraception method to prevent pregnancy,
and agree not to donate sperm from the time of the first injection through the end
of the study.
16. Willing and able to comply with all study assessments and adhere to the protocol
schedule and restrictions.
17. MRI Screening: Tibio-femoral osteoarthritis with MRI based femoral B-score at
Screening of 0.5 or greater in at least one knee as determined by central analysis.
Exclusion Criteria.Subjects are excluded from the study if any of the following criteria are met:
1. Contraindication to MRI.
2. Demonstrated clinically significant (required intervention, e.g., emergency room
visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic
reactions, asthmatic episodes) which, in the opinion of the Investigator, would
interfere with the volunteer's ability to participate in the trial.
3. Prior surgery in the target knee, excluding procedures for debridement only (no
previous micro-fracture procedure).
4. Knee joint replacement or any other knee surgery planned in either knee while
participating in the study.
5. Moderate or severe pain in the contralateral (non-target) knee.
6. History of fibromyalgia, rheumatoid arthritis (RA), psoriatic arthritis, or any
other autoimmune or infectious cause for arthritis; or referred knee pain from hip
or spinal disease.
7. Knee effusion >2+ on the following clinical scale:
1. Zero = No wave produced on down stroke. 2. Trace = Small wave on medial side with down stroke. 3. 1+ = Larger bulge on medial side with down stroke. 4. 2+ = Effusion spontaneously returned to medial side after upstroke (no down
stroke necessary)
5. 3+ = So much fluid that it was not possible to move the effusion out of the
medial aspect of the knee. 8. Last viscosupplementation (e.g., Synvisc® or similar hyaluronic acid product)
injected into either knee < 3 months before Screening.
9. Last IA injection of corticosteroids < 2 months before Screening.
10. Current (within previous month before Screening) of use of any systemic steroids
(except inhaled corticosteroids for allergy or respiratory problems).
11. Known hypersensitivity to any of the study drug ingredients.
12. Known hypersensitivity to acetaminophen or hydrocodone.
13. History of arthroscopy in the target knee in the 3 months before Screening.
14. History of septic arthritis, gout, or pseudo-gout in either knee in the year before
Screening.
15. Clinical signs in the opinion of the Investigator of acute meniscal tear (e.g.
locking or acute mechanical signs or symptoms consistent with meniscal tear) in
either knee.
16. Skin lesion, rash, infection, or hypersensitivity in the target knee at or near the
injection site at Screening.
17. Bleeding problems, platelet or coagulation deficiency that, in the option of the
Investigator, contraindicates IA injection.
18. Active systemic infection at Screening or immediately pre-dose on any IA injection
day, including chronic viral infection.
19. Current treatment or treatment within 2 years prior to Screening for any malignancy
except basal cell or squamous cell carcinoma of the skin, prostate or cervical
cancer in situ, unless with specific written permission provided by the Sponsor's
Medical Monitor.
20. Women of childbearing potential who are pregnant, nursing, or planning to become
pregnant, and women or men who do not agree to remain on an acceptable method of
birth control throughout the entire study period.
21. Participation in other clinical OA drug studies within 1 year prior to Screening
except epidemiologic studies involving no drug treatment.
22. Any participation in other clinical OA stem cell or gene therapy studies.
23. Currently taking paclitaxel (mitotic inhibitor), natalizumab (anti-integrin
monoclonal antibody), or any other anti-integrin treatment.
24. Routine consumption of more than 3 alcoholic drinks a day (definition of 1 alcoholic
drink:
- - 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5- ounces or a
"shot" of 80-proof distilled spirits or liquor such as gin, rum, vodka, or
whiskey).
25. History of substance abuse in the opinion of the Investigator within the two years
prior to Screening.
