A Study to Evaluate the Efficacy, Safety and Tolerability of EVI-01 Intra-Articular Injection in Osteoarthritis of the Knee

A Double-Blind, Randomized, Controlled, Three Parallel Arm, Dose-Finding Study to Evaluate the Efficacy, Safety and Tolerability of One Single Intra-Articular Injection of EVI-01 in Patients With Symptomatic Osteoarthritis of the Knee

Objective: Identifying the dose of EVI-01 with the best clinical response, balancing the efficacy, safety, and tolerability of the investigational product.

Study design: Interventional, dose-finding, three arms, randomized (1:1:1), parallel assignment, double-blind, controlled by an active comparator.

Phase II, dose-finding, interventional, three-arm, randomized (1:1:1), double-blind, parallel, active-comparator-controlled clinical trial.

Inclusion Criteria:

1. Patients of both genders aged 18 years or older;
2. Body Mass Index (BMI) < 35 kg/m2;
3. Diagnosis of primary knee osteoarthritis, Kellgren-Lawrence Grade 2 to 4, according to American College of Rheumatology (ACR) criteria and confirmed radiologically within the previous 12 months, for which an intraarticular treatment is indicated;
4. Moderate to severe pain measured by VAS (0-100mm) and >40mm in the knee to be treated, partially responsive to chronic doses of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, or weak opioids (codeine and tramadol);
5. Ability to understand and provide signed consent through the Informed Consent Form (ICF).

Exclusion Criteria:

1. History of hypersensitivity/allergy to hyaluronic acid (HA) or other excipients of the IP or product;
2. Pregnant or breastfeeding women;
3. Women at menace who do not agree to use acceptable contraceptive methods (oral contraceptive, injectable contraceptive, IUD, hormonal implant, barrier methods, sexual abstinence, hormone transdermal patch and tubal ligation); except those who are surgically sterile (bilateral oophorectomy or hysterectomy);
4. Emotional problems or any situation that, at the Investigator's discretion, places the safety of subjects at risk;
5. Application of visco-supplementation to the knee less than four months prior to randomization;
6. Corticosteroid IA injection less than 4 months prior to randomization and/or schedule during the course of the study;
7. Knee infection and/or inflammation (e.g., bursitis), skin infection at or around the IA injection;
8. Swelling, redness, warmth, or other clinically relevant inflammatory signs in the knee in the investigator's description
9. Knee injury or trauma;
10. Patients with bleeding diathesis or on anticoagulant therapy;
11. Major knee malformations or deformities that the investigator deems pertinent;
12. Active cancer at the Investigator's discretion;
13. Continuous or frequent use (use for more than 2 weeks in the last 2 months) of corticosteroids by any route of administration (oral, IM, IV)
14. Concomitant use of chondroprotective drugs such as glucosamine, chondroitin, or collagen. These medications should not be introduced during the study, but if the patient is already taking them may be included, but the medication will not change.
15. Need for the use of strong opioids (methadone, fentanyl, morphine, and oxycodone) for pain management;
16. Participation in a clinical trial within the last twelve months prior to enrollment (CNS Resolution 251, dated 07 August 1997, item III, item J), unless the investigator believes that there may be a benefit to the patient.