This study is a prospective, multicenter (up to 4 sites), randomized, double-blind, two-arm study. Forty-five (45) patients will be randomized to receive a single 4-6 ml intra-articular (IA) injection of either the output of ACP Max™ (n=30) or 6 ml of Depo-Medrol® (methylprednisolone acetate) (n=15).

All subjects will have a screening visit and a treatment visit followed by six follow-up visits: 10 days, 6 weeks, 3 months, 6 months, 9 months, and 12 months.

Inclusion Criteria:

1. Subject voluntarily decides to participate and signs the consent form.
2. Subject is ≥ 18 to 75 years of age.
3. Subject presents with symptomatic knee OA despite at least 6 months of one of the following conservative treatments; oral medications, analgesics, and/or anti-inflammatory medications.
4. Subject has documented radiographic evidence of OA in the tibiofemoral or patellofemoral compartment of the target knee (Kellgren-Lawrence Grades II-III), using radiographs performed within 12 weeks of screening.
5. Subject has a WOMAC pain score (WOMAC A) of at least 8 out of 20 and at least moderate degree of difficulty (a score of 2) for at least 2 questions on performing daily activities.
6. Subject consents to a washout period of NSAIDs and analgesics 7 days before each study visit (except low-dose aspirin for prevention of cardiovascular disease).
7. Subject has a Body Mass Index ≤ 35 kg/m2

Exclusion Criteria:

1. Subject has Grade I or IV in the target knee according to the Kellgren-Lawrence grading scale.
2. Subject has clinically 3+ effusion of the target knee (stroke test grading system).
3. Subject has significant (> 10°) valgus or varus deformities as evidenced by standard of care x-ray.
4. Subject has received an IA injection of corticosteroids in the target knee within 4 months prior to screening.
5. Subject did not achieve initial pain relief from prior corticosteroid injections.
6. Subject has received an IA injection of HA in the target knee within 6 months prior to screening.
7. Subject has received an IA injection of PRP in the target knee at any time prior to screening.
8. Subject has a history of coagulopathy.
9. Subject has joint pain reflected by a VAS score of > 35 mm out of 100 mm scale in the contralateral knee at the time of screening.
10. Subject had prior open surgery on the target knee within 12 months or knee arthroscopy within 6 months.
11. Subject has an inflammatory disease of either knee other than OA.
12. Subject which, in the investigator's opinion, has an underlying medical condition(s) that could interfere with the evaluation of the outcome.
13. Subject with a positive pregnancy test or breastfeeding.
14. Subject plans to participate in other clinical trials involving medical or surgical intervention in the next 12 months.
15. Subject with any condition (including cognitive impairment) that, in the investigator's opinion, might interfere with the evaluation of the study objectives.
16. Subject has rheumatoid arthritis or gout.
17. Subject has an infection at the affected joint.
18. Subject has a history of major trauma to the target knee within one year.
19. Subject with plans to undergo any elective orthopedic surgery in the next 12 months.
20. Subject requires pain management therapy not related to the target knee (with the exception of acetaminophen).
21. Subject has a known hypersensitivity to Depo-Medrol and its constituents.

This is a double-blind study where subjects and evaluators are blinded to treatment.