DONATELLO: Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis

Sponsor

Genascence Corporation (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05835895

Collaborator

California Institute for Regenerative Medicine (CIRM) (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The goal of this clinical study is to determine if a single injection of 1 or more dose levels of adeno-associated virus (AAV) gene therapy (GNSC-001) is safe and tolerated compared to placebo in participants with painful osteoarthritis (OA) of the knee.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee Osteo Arthritis Knee Knee Osteoarthritis Knee Pain Chronic Knee Arthritis Musculoskeletal Diseases Joint Diseases Osteoarthritis Arthritis Knee Inflammatory Arthritis	Genetic: GNSC-001 Drug: transient immune-modulation Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 1b, Randomized, Double-Blinded, Placebo-Controlled Dose Ranging Study to Evaluate Safety, Tolerability and Pharmacodynamics of a Single Intra-articular Injection of GNSC-001 Gene Therapy in Subjects With Osteoarthritis of the Knee

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GNSC-001 (low dose)	Genetic: GNSC-001 intra-articular injection Other Names: sc-rAAV2.5IL-1Ra
Experimental: GNSC-001 (low dose) + transient immune-modulation	Genetic: GNSC-001 intra-articular injection Other Names: sc-rAAV2.5IL-1Ra Drug: transient immune-modulation oral
Experimental: GNSC-001 (high dose)	Genetic: GNSC-001 intra-articular injection Other Names: sc-rAAV2.5IL-1Ra
Experimental: GNSC-001 (high dose) + transient immune-modulation	Genetic: GNSC-001 intra-articular injection Other Names: sc-rAAV2.5IL-1Ra Drug: transient immune-modulation oral
Placebo Comparator: Placebo	Drug: Placebo intra-articular injection

Outcome Measures

Primary Outcome Measures

Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [Month 12]
Severity of TEAEs and SAEs [Month 12]

Secondary Outcome Measures

Change in synovial Interleukin-1 Receptor Antagonist (IL-1Ra) levels over time, from Baseline [Baseline to Month 1, 3, 6, 12, and 24]

Other Outcome Measures

Immunogenicity of a single dose of GNSC-001 [Month 6 and 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

OA in at least one knee (the 'target knee'), confirmed using centrally read X-ray with a Kellgren-Lawrence (KL) score of 2 or 3
Western Ontario & McMaster University Osteoarthritis Index (WOMAC) pain score ≥ 20 (on a 50-point numerical rating scale) in the target knee during the seven days prior to Screening
Persistent moderate to severe symptoms in the target knee, despite failure or intolerance of a 3-month trial of at least 2 conservative therapies (e.g., activity modification, weight loss, physical therapy, opioids, and anti-inflammatory medications, and injection of hyaluronic acid or steroids)
Presence of synovial fluid on ultrasound and/or high likelihood of successful extraction of synovial fluid
Negative pregnancy test at Screening and Baseline (women of childbearing potential [WOCBP])

Key Exclusion Criteria:

Current or documented history of inflammatory arthritis (such as gout or rheumatoid arthritis), inflammation of connective tissue, or other immunological disease
Any form of joint degeneration as part of another syndrome (e.g., Ehler's Danlos, Stickler syndrome, etc.)
Surgery in the target knee within the 6 months prior to screening
Previous partial or total joint replacement in target knee
Significant and clinically evident malalignment of the target knee that would impact the subject's function, as determined by the Investigator
Body mass index (BMI) > 38 kg/m2
Clinically significant abnormal laboratory values at Screening in laboratory parameters that in the opinion of the Investigator, could represent a potential risk to participant safety:
Plans to have, elective surgery of other joints or spine or intra-articular injections in the target knee, within the next 12 months