Osteoarthritis, KneePhase 1DONATELLONCT05835895
Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis
A Phase 1 study testing GNSC-001 and transient immune-modulation in people with Osteoarthritis, Knee and Osteo Arthritis Knee, run by Genascence Corporation at 9 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Osteoarthritis, Knee, Osteo Arthritis Knee, Knee Osteoarthritis
- What is being tested?
- GNSC-001 and transient immune-modulation
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 9 sitesUnited States
- Study dates
- 12 Jun 2023to May 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- Successful extraction of synovial fluid at Screening
- Negative pregnancy test at Screening and Baseline (subjects of childbearing potential [SOCBP])
Who cannot join
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
Alliance for Multispecialty Research Kansas City
Kansas City, Missouri, 64114
Biosolutions Clinical Research Center
La Mesa, California, 91942
Well Pharma Medical Research
Miami, Florida, 33173
South Florida Research
Miami Springs, Florida, 33166
Alliance for Medical Research Mobile
Mobile, Alabama, 36608
West Clinical Research
Morehead City, North Carolina, 28557
UC San Diego
San Diego, California, 92037
Premier Medical Associates
The Villages, Florida, 32159
About this study
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
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.
- Being tested
- GNSC-001, transient immune-modulation, Placebo
- Keywords
- Gene therapy, Adeno-associated virus, Intra-articular, GNSC-001, Genascence, Knee pain, Knee arthritis, Osteoarthritis
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GNSC-001Genetic
Also called sc-rAAV2.5IL-1Ra
intra-articular injection
transient immune-modulationDrug
oral
transient immune-modulationDrug
intra-articular injection
PlaceboDrug
intra-articular injection
| Study group | Role | What they receive |
|---|---|---|
| GNSC-001 (low dose) | Experimental | Not described Receives: Genetic: GNSC-001 |
| GNSC-001 (low dose) + transient immune-modulation (oral) | Experimental | Not described Receives: Genetic: GNSC-001; Drug: transient immune-modulation |
| GNSC-001 (high dose) | Experimental | Not described Receives: Genetic: GNSC-001 |
| GNSC-001 (high dose) + transient immune-modulation (oral) | Experimental | Not described Receives: Genetic: GNSC-001; Drug: transient immune-modulation |
| GNSC-001 (high dose) + transient immune-modulation (oral + injectable) | Experimental | Not described Receives: Genetic: GNSC-001; Drug: transient immune-modulation |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Measured: Month 12
Severity of TEAEs and SAEs
Measured: Month 12
Secondary outcomes (3)
Synovial fluid Interleukin-1 Receptor Antagonist (IL-1Ra) levels
Measured: Month 12
Synovial fluid Interleukin-1 Receptor Antagonist (IL-1Ra) levels
Measured: Months 1, 3, 6, and 24 months
Change in synovial Interleukin-1 Receptor Antagonist (IL-1Ra) levels over time
Measured: Baseline to Months 1, 3, 6, 12 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2023
- Study start12 Jun 2023
- Primary completion8 Apr 2025
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genascence Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Responsible party
- Sponsor
- Investigators
- Jeymi Tambiah, MBChB, Study director, Genascence Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05835895
- Sponsor's protocol ID
- CPRO-22-001
- Other IDs
- CLIN2-14265
- Acronym
- DONATELLO
- Status last verified
- Dec 2024
- First submitted
- 19 Apr 2023
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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):e70141. doi: 10.1002/jor.70141.
PubMed 41607103Chen L, Huang FL, Tang Q, Zhao ZK, Ye ZY, Liang JH. Targeted therapy for knee osteoarthritis: From basic to clinics. Medicine (Baltimore). 2025 Aug 15;104(33):e43686. doi: 10.1097/MD.0000000000043686.
PubMed 40826764Evans 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.
PubMed 39284030
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05835895
- Acronym / sponsor ID
- DONATELLO / CPRO-22-001
- Keywords
- Gene therapy, Adeno-associated virus, Intra-articular, GNSC-001, Genascence, Knee pain, Knee arthritis, Osteoarthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Genascence CorporationIndustry (pharma, biotech, devices)
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Study start
- 12 Jun 2023 (actual)
- Primary completion
- 8 Apr 2025 (actual)
- Study completion
- May 2029 (estimated)
- First posted
- 28 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| GNSC-001 (low dose) | Experimental | Genetic: GNSC-001 |
| GNSC-001 (low dose) + transient immune-modulation (oral) | Experimental | Genetic: GNSC-001, Drug: transient immune-modulation |
| GNSC-001 (high dose) | Experimental | Genetic: GNSC-001 |
| GNSC-001 (high dose) + transient immune-modulation (oral) | Experimental | Genetic: GNSC-001, Drug: transient immune-modulation |
| GNSC-001 (high dose) + transient immune-modulation (oral + injectable) | Experimental | Genetic: GNSC-001, Drug: transient immune-modulation |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
- Successful extraction of synovial fluid at Screening
- Negative pregnancy test at Screening and Baseline (subjects of childbearing potential [SOCBP])
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GNSC-001Also: sc-rAAV2.5IL-1Raintra-articular injection | Genetic | GNSC-001 (high dose), GNSC-001 (high dose) + transient immune-modulation (oral + injectable), GNSC-001 (high dose) + transient immune-modulation (oral), GNSC-001 (low dose), GNSC-001 (low dose) + transient immune-modulation (oral) |
| transient immune-modulationoral | Drug | GNSC-001 (high dose) + transient immune-modulation (oral + injectable), GNSC-001 (high dose) + transient immune-modulation (oral), GNSC-001 (low dose) + transient immune-modulation (oral) |
| transient immune-modulationintra-articular injection | Drug | GNSC-001 (high dose) + transient immune-modulation (oral + injectable) |
| Placebointra-articular injection | Drug | Placebo |
Primary outcome
Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time frame: Month 12
Severity of TEAEs and SAEs
Time frame: Month 12
3 secondary outcomes
Synovial fluid Interleukin-1 Receptor Antagonist (IL-1Ra) levels
Time frame: Month 12
Synovial fluid Interleukin-1 Receptor Antagonist (IL-1Ra) levels
Time frame: Months 1, 3, 6, and 24 months
Change in synovial Interleukin-1 Receptor Antagonist (IL-1Ra) levels over time
Time frame: Baseline to Months 1, 3, 6, 12 and 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Derived from this study: PubMed 41607103Evans CH, Ghivizzani SC, Robbins PD. Osteoarthritis Gene Therapy: A 30-Year Journey From Concept to Clinical Trials. J Orthop Res. 2026 Feb;44(2):e70141. doi: 10.1002/jor.70141.
- Derived from this study: PubMed 40826764Chen L, Huang FL, Tang Q, Zhao ZK, Ye ZY, Liang JH. Targeted therapy for knee osteoarthritis: From basic to clinics. Medicine (Baltimore). 2025 Aug 15;104(33):e43686. doi: 10.1097/MD.0000000000043686.
- Derived from this study: PubMed 39284030Evans 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeymi Tambiah, MBChB study director
Genascence Corporation
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GNSC-001 and transient immune-modulation in people with Osteoarthritis, Knee and Osteo Arthritis Knee, run by Genascence Corporation at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) (time frame: Month 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05835895, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2025.