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

NCT02790723 | Completed Phase 1 FDA Drug

• 1 other identifier: 15-007542
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoarthritis, Knee

Outcome Measures

Primary Outcomes (1)

• Number of subjects experiencing severe adverse events.

  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.

  53 weeks

Study Arms (3)

Low Dose Group

EXPERIMENTAL

Subjects will receive a single intra-articular 2mL injection consisting of 10{11} viral genomes.

Drug: sc-rAAV2.5IL-1Ra

Medium Dose Group

EXPERIMENTAL

Subjects will receive a single intra-articular 2mL injection consisting of 10{12} viral genomes.

Drug: sc-rAAV2.5IL-1Ra

High Dose Group

EXPERIMENTAL

Subjects will receive a single intra-articular 2mL injection consisting of 10{13} viral genomes.

Drug: sc-rAAV2.5IL-1Ra

Interventions

sc-rAAV2.5IL-1Ra DRUG

Self-complementing, recombinant AAV carrying IL-1Ra cDNA produced by the Research Institute at Nationwide Children's Hospital.

Also known as: AAVIL-1Ra, IL-1Ra

High Dose Group; Low Dose Group; Medium Dose Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 in the index knee
• Prior reconstruction surgery to the target knee within 12 months
• X-ray findings of acute fractures

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (5)

• Evans CH, Ghivizzani SC, Robbins PD. Osteoarthritis Gene Therapy: A 30-Year Journey From Concept to Clinical Trials. J Orthop Res. 2026 Feb;44(2). doi: 10.1002/jor.70141.

  PMID: 41607103 DERIVED

• Evans CH, Ghivizzani SC, Robbins PD. The 2024 OREF Clinical Research Award: Progress Toward a Gene Therapy for Arthritis. J Am Acad Orthop Surg. 2024 Dec 1;32(23):1052-1060. doi: 10.5435/JAAOS-D-24-00831. Epub 2024 Oct 17.

  PMID: 39284030 DERIVED

• 2022 AMSSM Rising With Research Presentations. Clin J Sport Med. 2022 Mar 1;32(2):168-176. doi: 10.1097/JSM.0000000000001014. No abstract available.

  PMID: 35234744 DERIVED

• 2021 AMSSM Oral Research Poster Presentations. Clin J Sport Med. 2021 Mar 1;31(2):185-221. doi: 10.1097/JSM.0000000000000914. No abstract available.

  PMID: 33647918 DERIVED

• Mehta S, He T, Bajpayee AG. Recent advances in targeted drug delivery for treatment of osteoarthritis. Curr Opin Rheumatol. 2021 Jan;33(1):94-109. doi: 10.1097/BOR.0000000000000761.

  PMID: 33229973 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Christopher H. Evans, Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: June 6, 2016
• Study Start: June 5, 2019
• Primary Completion: March 17, 2022
• Study Completion: March 17, 2022
• Last Updated: April 15, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)