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

December 5, 2025 updated by: Aptissen SA

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Brazil
      • São Paulo, Brazil
        • Ortocity
    • São Paulo
      • Valinhos, São Paulo, Brazil
        • A2Z Clinical

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Synvisc-One
6 mL, one single intra-articular injection
Device: Active comparator Synvisc-One
Single intra-articular injection of active comparator Synvisc-One
Experimental: EVI-01 - low dose
4 mL, one single EVI-01 intra-articular injection
Device: EVI-01
Single intra-articular injection of high molecular weight hyaluronic acid
Experimental: EVI-01 - high dose
6 mL, one single EVI-01 intra-articular injection
Device: EVI-01
Single intra-articular injection of high molecular weight hyaluronic acid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes to the questionnaire WOMAC A (Western Ontario and McMaster Universities) Numeric 3.1
Time Frame: from baseline to 180 days after randomization
Questionnaire WOMAC A (Western Ontario and McMaster Universities) numeric scale, version 3.1, total knee pain score (pain, stiffness and physical function assessment)
from baseline to 180 days after randomization
Comparison of treatment-related Adverse Events in the three groups
Time Frame: from baseline to 180 days after randomization
Incidence of treatment-emergent adverse events
from baseline to 180 days after randomization

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes to the WOMAC (Western Ontario and McMaster Universities) Total Numeric 3.1 score
Time Frame: from baseline to 180 days after randomization
WOMAC (Western Ontario and McMaster Universities) numeric scale, version 3.1 (pain, stiffness and physical function assessment)
from baseline to 180 days after randomization
Changes to the WOMAC (Western Ontario and McMaster Universities) A score
Time Frame: from Day 1 to Day 7 after randomization
WOMAC (Western Ontario and McMaster Universities) A numeric scale, version 3.1, total knee pain score (pain, stiffness and physical function assessment)
from Day 1 to Day 7 after randomization
Response to the Euro Quality of Life Questionnaire
Time Frame: from baseline to 180 days after randomization
Euro Quality of Life Questionnaire version EQ-5D-5L
from baseline to 180 days after randomization
Response rate, according to OMERACT-OARSI2 international criteria
Time Frame: from baseline to Days 28, 90 and 180 after randomization
OMERACT-OARSI2 (Outcome Measures in Rheumatology Committee - Osteoarthritis Research Society International)
from baseline to Days 28, 90 and 180 after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aptissen SA

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Azidus Brasil

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Guilherme Gracitelli, MD, C.E.P.O.T. - Centro de Estudos e Pesquisas em Ortopedia e Traumatologia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 17, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 29, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 29, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 14, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 14, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 20, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 8, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EVI-01-BR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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