Gene Therapy for Knee Osteoarthritis

(DONATELLO Trial)

Recruiting at 9 trial locations

Overseen By Eddie Armas, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genascence Corporation

Disqualifiers: Inflammatory arthritis, Joint degeneration, Surgery, others

Compensation: Varies

Number of Visits: 5

Duration: 1 day

67 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for people with painful knee osteoarthritis. The treatment uses a special virus to deliver a helpful gene directly into the knee. Researchers want to see if this single injection is safe and well-tolerated.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have persistent symptoms despite trying conservative therapies, which might include medications like opioids and anti-inflammatory drugs.

What data supports the effectiveness of the treatment GNSC-001 for knee osteoarthritis?

Research on gene therapy for osteoarthritis shows that using viral vectors to deliver therapeutic genes can provide long-term relief and improve joint function. In particular, studies have shown that genetically engineered cells expressing certain proteins can reduce pain and slow cartilage damage in knee osteoarthritis, suggesting potential benefits for treatments like GNSC-001. ^{1 2 3 4 5}

Is gene therapy for knee osteoarthritis safe for humans?

Gene therapy for knee osteoarthritis, specifically using TG-C, has been shown to be generally safe in humans, with no severe adverse events reported. Common side effects like joint pain and inflammation were similar to those seen with placebo treatments. ^{1 2 3 6 7}

What makes the treatment GNSC-001 unique for knee osteoarthritis?

GNSC-001 is a gene therapy that uses genetically engineered chondrocytes to deliver TGF-β1 directly into the knee joint, promoting cartilage repair and reducing inflammation, which is different from traditional treatments that typically focus on pain relief and inflammation control without directly repairing cartilage. ^{1 8 9 10 11}

Research Team

Jeymi Tambiah, MBChB

Principal Investigator

Genascence Corporation

Eligibility Criteria

This trial is for adults with moderate to severe knee osteoarthritis, confirmed by X-ray and pain scores. Participants must have tried at least two conservative treatments without success and be able to provide a synovial fluid sample. Exclusions include recent knee surgery, BMI over 38, significant lab abnormalities, planned surgeries or injections in the next year, inflammatory arthritis history, joint replacement in the target knee, or degeneration from other syndromes.

Inclusion Criteria

Negative pregnancy test at Screening and Baseline (subjects of childbearing potential [SOCBP])

My knee arthritis is moderate to severe, confirmed by an X-ray.

My knee pain score is 20 or more out of 50.

Exclusion Criteria

I have or had inflammatory arthritis, connective tissue inflammation, or an immune disease.

I plan to have surgery or injections in my knee or other joints within a year.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intra-articular injection of GNSC-001 gene therapy or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and tolerability after the injection

12 weeks

4 visits (in-person)

Treatment Details

Interventions

• GNSC-001
• Placebo
• Transient Immune-modulation

Trial Overview The study tests if a single injection of GNSC-001 gene therapy is safe compared to placebo for those with painful knee osteoarthritis. It explores different dose levels of this AAV gene therapy which aims for transient immune-modulation to alleviate symptoms.

Participant Groups

Group I: GNSC-001 (low dose) + transient immune-modulation (oral) Experimental Treatment 2 Interventions

Group II: GNSC-001 (low dose) Experimental Treatment 1 Intervention

Group III: GNSC-001 (high dose) + transient immune-modulation (oral) Experimental Treatment 2 Interventions

Group IV: GNSC-001 (high dose) + transient immune-modulation (oral + injectable) Experimental Treatment 2 Interventions

Group V: GNSC-001 (high dose) Experimental Treatment 1 Intervention

Group VI: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Genascence Corporation

Lead Sponsor

Trials

1

Recruited

70+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

References

1. Germany pubmed.ncbi.nlm.nih.gov

Results of a Phase II Study to Determine the Efficacy and Safety of Genetically Engineered Allogeneic Human Chondrocytes Expressing TGF-β1. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Advances and challenges in gene-based approaches for osteoarthritis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

rAAV-mediated overexpression of TGF-β stably restructures human osteoarthritic articular cartilage in situ. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Getting arthritis gene therapy into the clinic. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Optimization of a nonviral transfection system to evaluate Cox-2 controlled interleukin-4 expression for osteoarthritis gene therapy in vitro. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of FX201, a Novel Intra-Articular IL-1Ra Gene Therapy for Osteoarthritis Treatment, in a Rat Model. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-β1 in patients with grade 3 chronic degenerative joint disease of the knee. [2018]

9. Iran pubmed.ncbi.nlm.nih.gov

The Role of Gene Therapy in Cartilage Repair. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Pre-clinical studies of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 (TG-C). [2018]

11. United States pubmed.ncbi.nlm.nih.gov

In vitro gene transfer to chondrocytes and synovial fibroblasts by adenoviral vectors. [2013]