Safety of Intra-Articular Sc-rAAV2.5IL-1Ra in Subjects With Moderate Knee OA (AAVIL-1Ra)

• ClinicalTrials.gov Identifier: NCT02790723
• Recruitment Status: Recruiting
• First Posted: June 6, 2016
• Last Update Posted: October 16, 2019
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Christopher H. Evans, Ph.D., Mayo Clinic

Study Description

Brief Summary:

This study seeks to determine the safety of three different doses of sc-rAAV2.5IL-1Ra delivered by intra-articular injection into one knee joint of patients with moderate OA of the knee.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee	Drug: sc-rAAV2.5IL-1Ra	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 9 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study Evaluating the Safety of Intra-Articular Sc-rAAV2.5IL-1Ra in Subjects With Moderate Osteoarthritis of the Knee
• Actual Study Start Date: June 5, 2019
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: May 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low Dose Group; Subjects will receive a single intra-articular 10mL injection consisting of 10{11} viral genomes.	Drug: sc-rAAV2.5IL-1Ra; Self-complementing, recombinant AAV carrying IL-1Ra cDNA produced by the Research Institute at Nationwide Children's Hospital.; Other Names: AAVIL-1Ra; IL-1Ra
Experimental: Medium Dose Group; Subjects will receive a single intra-articular 10mL injection consisting of 10{12} viral genomes.	Drug: sc-rAAV2.5IL-1Ra; Self-complementing, recombinant AAV carrying IL-1Ra cDNA produced by the Research Institute at Nationwide Children's Hospital.; Other Names: AAVIL-1Ra; IL-1Ra
Experimental: High Dose Group; Subjects will receive a single intra-articular 10mL injection consisting of 10{13} viral genomes.	Drug: sc-rAAV2.5IL-1Ra; Self-complementing, recombinant AAV carrying IL-1Ra cDNA produced by the Research Institute at Nationwide Children's Hospital.; Other Names: AAVIL-1Ra; IL-1Ra

Outcome Measures

Primary Outcome Measures :

1. Number of subjects experiencing severe adverse events. [ Time Frame: 53 weeks ]
   Assess the local and systemic safety of three different doses of sc-rAAV2.5IL-1Ra delivered by intra-articular injection into one knee joint of patients with moderate OA of the knee.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

• Age 18-80 years
• Gender: both males and females
• Target disease: Moderate OA of the knee
• Persistent symptoms, despite standard NSAID
• Absence of clinically significant abnormal values for the following:
• Complete blood count
• Prothrombin Time, Activated partial thromboplastin time
• Blood chemistry (Glucose, Na, K, Cl, CO2, BUN, creatinine, Ca, PO4, magnesium, uric acid)
• Liver function tests (amylase, total bilirubin, alkaline phosphate, GGT, AST, ALT, total protein, albumin)
• Able and willing to return to the Mayo Clinic for follow-up visits, as required by this study
• Able undergo MRI of the knee
• Subjects should be able to give appropriate consent.
• Potential subjects should have failed a three-month trial of a minimum of two conservative therapies before being considered for this trial. These conservative therapies include: activity modification, weight loss, physical therapy, and anti-inflammatory or injection therapy.

Exclusion Criteria

• Pregnant, or currently breast-feeding
• Ongoing infectious disease including HIV, HTLV, hepatitis, syphilis or tuberculosis positive
• Individuals who have OA as part of another syndrome (e.g. Ehler's Danlos, Stickler syndrome, etc.)
• Systemic, rheumatic or inflammatory disease of the knee or chondrocalcinosis, hemochromatosis, inflammatory arthritis, arthropathy of the knee associated with juxta-articular Paget's disease of the femur or tibia, ochronosis, hemophilic arthropathy, infectious arthritis, Charcot's knee joint, villonodular synovitis, and synovial chondromatosis.
• Clinically significant cardiovascular, renal, hepatic, endocrine disease, diabetes, cancer, autoimmune diseases; a serious infection or major operation within 30 days of enrollment; a history of untreated psychiatric disease or recent history of alcoholism or drug addiction.
• Currently taking immunosuppressant medications
• Anticipated major surgery during the study period.
• Individuals involved in another interventional protocol, or have been treated under one within the last 3 months.
• Intra-articular therapy in the index knee within the previous 3 months.
• Surgery to the target knee within 6 months prior to screening.
• Surgery to other weight bearing joints if it will interfere with knee assessments
• Prior articular transplant procedures
• Orthopedic hardware or implantable devices anywhere in the body, other than dental
• Prior reconstruction surgery to the target knee within 12 months
• X-ray findings of acute fractures
• Known severe loss of bone density, and/or severe bone or joint deformity in the target knee.
• Significant target knee infection or overlying skin disorder/infection within the previous 6 months prior to study enrollment
• Require cane or other assistive device for walking
• Symptomatic OA of the hips, spine or ankle if it would interfere with the evaluation of the target knee,
• History of documented nerve damage in the affected limb, or vascular insufficiency,
• Condition requiring use of systemic steroids,
• Coagulation disorder.
• Patients with unstable knees
• Temperature above 99.5o F.
• Identification as a member of a vulnerable population.
• BMI greater than 40.
• History of allergy to local anesthetics
• Currently taking anti-rheumatic disease medication (including methotrexate or other antimetabolites) within the 3 months prior to entry in the study.
• Any illness or condition which, in the investigators' judgement will interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of the study results

Contacts and Locations

Contacts

Contact: Tyson L. Scrabeck; (507)538-1016; scrabeck.tyson@mayo.edu

Contact: Julie B. Block; (507)255-7393; block.julie@mayo.edu

Locations

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Tyson L. Scrabeck scrabeck.tyson@mayo.edu

Contact: Julie B. Block block.julie@mayo.edu

Principal Investigator: Jay Smith, M.D.

Sub-Investigator: Matthew A. Frick, M.D.

Sub-Investigator: Jacob L. Sellon, M.D.

Sub-Investigator: Steven J. Wisniewski, M.D.

Sponsors and Collaborators

Mayo Clinic

Investigators

• Principal Investigator: Christopher H. Evans, Ph.D.; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Christopher H. Evans, Ph.D., PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02790723
• Other Study ID Numbers: 15-007542
• First Posted: June 6, 2016
• Last Update Posted: October 16, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Interleukin 1 Receptor Antagonist Protein; Antirheumatic Agents