Genascence Initiates Knee Osteoarthritis Gene Therapy Trial


An investigator-initiated trial presented positive data at the ESGCT annual meeting in October 2023.

Lachy McLean, MD, PhD

Lachy McLean, MD, PhD

Genascence has initiated the phase 1B DONATELLO clinical trial (NCT05835895) investigating GNSC-001 adeno-associated virus (AAV) vector gene therapy for the potential treatment of knee osteoarthritis.1

"Osteoarthritis is incapacitating, causing years of pain and disability for people living with the disease, and there are no currently available treatments to slow down disease progression," Thomas Chalberg, PhD, founder and CEO, Genascence, said in a statement.1 "We are excited that our Phase 1B DONATELLO clinical trial is now fully up and running at 10 clinical sites across the US. This is a critical next step toward the development of the first gene therapy for prevalent musculoskeletal diseases like OA."

The dose-ranging, randomized, double-blind, placebo-controlled DONATELLO trial is currently enrolling approximately 50 participants at 10 clinical centers throughout the US.The trial is evaluating the safety, tolerability and pharmacodynamics of a single, intra-articular injection of GNSC-001 in patients with knee OA. Genascence plans to complete enrollment in the first quarter of 2024, with topline, 6-month data expected in the fourth quarter of 2024.

GNSC-001 uses a recombinant AAV vector to deliver an optimized form of IL-1Ra designed to block interleukin-1 (IL-1) signaling, which contributes to inflammation, joint pain, and cartilage destruction in knee OA.

READ MORE: Cell Therapy Not Superior to Corticosteroid Injections for Knee Osteoarthritis

"Our GNSC-001 gene therapy has the potential to transform the treatment landscape for individuals suffering from OA," Lachy McLean, MD, PhD, chief medical officer, Genascence, added.1 "We look forward to sharing initial 6-month data from the DONATELLO clinical trial in the fourth quarter of 2024 and continue advancing our clinical program so we can bring a new option to patients as quickly as possible."

Genascence recently presented data from an investigator-initiated phase 1 trial (NCT02790723) at Mayo Clinic of GNSC-001 at the European American Society of Gene & Cell Therapy's (ESGCT) 30th Annual Congress, held October 24-27, 2023, in Brussels, Belgium. The data demonstrated that the gene therapy was well-tolerated and elevated IL-1Ra expression in synovial fluid, sustained for the study’s 12-month duration. Patients also had positive trends in pain scores via Visual Analogue Scale (VAS), pain and function via WOMAC scores, and limited disease progression.2

The phase 1 trial treated 9 participants in 3 cohorts of 1x1011 vector genomes (vg)/knee (low dose), 1x1012 vg/knee (mid dose), or 1x1013 vg/knee (high dose) GNSC-001 delivered by intra-articular injection. Investigators observed no dose-limiting toxicities up to 1x1013 vg high dose. Two participants experienced vector-related adverse events of mild/moderate knee effusions, which resolved with ice and rest.

All participants developed various degrees of anti-AAV neutralizing antibodies after injection, but no capsid targeted T-cell response was detected. Investigators found small amounts of viral genomes in peripheral blood, starting 1 day after injection before clearing within 4 weeks in most participants.

"These study results provide encouraging preliminary evidence that GNSC-001 may have a role to play in helping OA patients in a safe and effective manner," Annahita Keravala, PhD, founder and chief scientific officer, Genascence, said in a statement regarding the data update.2

1. Genascence announces initiation of phase 1b clinical trial of GNSC-001 gene therapy for knee osteoarthritis (OA). News release. Genascence.
2. Genascence to Present Full Data from Phase 1 Clinical Trial on GNSC-001, Company's Lead Program in Osteoarthritis, at European Society of Gene & Cell Therapy 30th Annual Congress. News release. Genascence.
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