NOVOCART 3D vs Microfracture for Knee Cartilage Defects

(N3D Trial)

Not currently recruiting at 45 trial locations

Overseen By Sarah Collins

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Aesculap Biologics, LLC

Disqualifiers: Arthritis, Autoimmune, Immune suppression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post-randomization

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for knee cartilage defects to determine which one is more effective. One treatment, NOVOCART 3D, uses a special scaffold to promote cartilage cell growth. The other is a more common method called Microfracture, an articular cartilage repair technique. The main goal is to identify which treatment more effectively reduces pain and improves knee function. Individuals with knee cartilage damage between 2-6 cm² who experience pain or difficulty using their knee might be suitable candidates. The trial also evaluates the safety of both treatments. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to the development of potentially groundbreaking treatments.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NOVOCART 3D has been tested in earlier studies for knee cartilage problems. These studies found that most patients tolerate NOVOCART 3D well. In one study, patients who received NOVOCART 3D experienced similar safety outcomes to those who underwent microfracture, a common method for repairing cartilage.

The studies suggest that serious side effects are rare. Most side effects are mild and may include temporary swelling or pain at the treatment site. Overall, the treatment appears to be as safe as other existing options. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard microfracture treatment for knee cartilage defects, which involves creating small fractures in the bone to stimulate healing, NOVOCART 3D uses a scaffold-assisted autologous chondrocyte implant. This innovative approach involves taking the patient's own cartilage cells, growing them, and then implanting them on a scaffold to repair the defect. Researchers are excited about NOVOCART 3D because it offers a more structured way to regenerate cartilage, potentially improving the quality and durability of the repair compared to traditional methods.

What evidence suggests that this trial's treatments could be effective for knee cartilage defects?

This trial will compare NOVOCART 3D with the microfracture method for treating knee cartilage defects. Research has shown that NOVOCART 3D, which uses a special support structure with the patient's own cartilage cells, holds promise for repairing knee cartilage damage. Studies comparing NOVOCART 3D to the traditional microfracture method have demonstrated better results in reducing pain and improving knee movement. Specifically, one study found that patients who received NOVOCART 3D reported improved knee function over three years. This treatment aims to restore knee cartilage more effectively than traditional methods by utilizing the body's own cells. These findings suggest that NOVOCART 3D could be a more effective option for individuals with knee cartilage damage. ^{1 2 3 4 5}

Who Is on the Research Team?

Robert Spiro, PhD

Principal Investigator

Octane Biotherapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with specific knee cartilage defects between 2-6 cm². Participants must have a certain level of pain and dysfunction as measured by the KOOS questionnaire. It's not for those with arthritis, unstable knees, immune issues, prior similar knee surgeries (except debridement/lavage after three months), bone diseases, degenerative conditions that affect healing or evaluation, or autoimmune diseases.

Inclusion Criteria

You need to have a certain score on the KOOS questionnaire.

I have a knee cartilage injury between 2-6 cm2.

I am older than 18 years.

Exclusion Criteria

My knee is unstable.

I have a bone condition.

You have an autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either NOVOCART 3D or Microfracture treatment for knee cartilage defects

Immediate post-randomization

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term follow-up

Participants continue to be monitored for safety and efficacy

Additional 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Microfracture
• NOVOCART 3D

Trial Overview The study compares NOVOCART 3D (a tissue-engineered cartilage implant) to Microfracture surgery (a technique where small holes are made in the bone beneath the damaged cartilage to stimulate new growth). The goal is to see which treatment better improves pain and function in the knee.

How Is the Trial Designed?

Group I: NOVOCART 3D Experimental Treatment 1 Intervention

Scaffold assisted autologous chondrocyte Implant

Group II: Microfracture Active Control 1 Intervention

considered a typical treatment for articular cartilage repair

Microfracture is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Microfracture for:

• Symptomatic focal articular cartilage lesions in the knee (femoral condyles or trochlea)

Approved in European Union as Microfracture for:

• Full-thickness defects or loss of the articular surface of a joint, usually the knee joint

Approved in Canada as Microfracture for:

• Damaged articular cartilage of the knee

Who Is Running the Clinical Trial?

Aesculap Biologics, LLC

Lead Sponsor

Trials

2

Recruited

260+

Published Research Related to This Trial

The NeoCart implant, used to repair cartilage lesions, demonstrated significant safety and efficacy over a 60-month follow-up in 29 patients, with improvements in cartilage quality and patient-reported outcomes (PROs) such as pain and function.

MRI analysis showed that the repair tissue matured from hyperintense to hypointense signals over time, indicating a transition to denser tissue, while clinical improvements peaked at 24 months and remained stable through 60 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Imaging Characterization and Clinical Outcomes After NeoCart Surgical Therapy as a Primary Reparative Treatment for Knee Cartilage Injuries. Anderson, DE., Williams, RJ., DeBerardino, TM., et al.[2019]

Enhanced microfracture procedures for treating focal cartilage injuries in the knee significantly improve patient-reported outcomes, indicating effectiveness in symptom relief, based on a review of 10 studies with 331 patients.

However, imaging results were inconsistent, and the reporting of treatment-related adverse events was inadequate, suggesting that while the procedure shows promise, further research is needed to fully endorse its use for grade III/IV cartilage lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced microfracture using acellular scaffolds improves results after treatment of symptomatic focal grade III/IV knee cartilage lesions but current clinical evidence does not allow unequivocal recommendation. da Cunha, CB., Andrade, R., Veloso, TR., et al.[2021]

Microfracture is an effective single-stage procedure for treating small cartilage defects, showing improvement in knee function for 70% to 90% of patients, especially in the first year after surgery.

The technique is cost-effective and has low patient morbidity, making it a valuable first-line treatment option, although outcomes may decline after one year, particularly in patients with a high body mass index or incomplete fibrocartilage fill.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microfracture: indications, technique, and results. Williams, RJ., Harnly, HW.[2022]

A systematic review of five comparative studies involving autologous chondrocyte implantation (ACI) and microfracture for knee cartilage lesions showed that both treatments significantly improve clinical outcomes after 5 years.

Modified versions of ACI, such as ACI with a collagen membrane (ACI-C) or matrix-applied chondrocyte implantation (MACI), resulted in better clinical results compared to microfracture, although the treatment failure rates were similar between the two methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is implantation of autologous chondrocytes superior to microfracture for articular-cartilage defects of the knee? A systematic review of 5-year follow-up data. Na, Y., Shi, Y., Liu, W., et al.[2019]

In a randomized trial involving 30 patients, the NeoCart autologous cartilage tissue implant demonstrated greater clinical efficacy compared to microfracture surgery, with significant improvements in pain and quality of life scores at six, twelve, and twenty-four months post-treatment.

The safety profile of NeoCart was similar to that of microfracture, with no significant differences in adverse event rates, indicating that NeoCart is a safe and effective alternative for treating articular cartilage injuries in the knee.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NeoCart, an autologous cartilage tissue implant, compared with microfracture for treatment of distal femoral cartilage lesions: an FDA phase-II prospective, randomized clinical trial after two years. Crawford, DC., DeBerardino, TM., Williams, RJ.[2022]

Microfracture is effective for improving knee function in the short term (up to 24 months) after treatment, based on a systematic review of 28 studies involving 3122 patients.

However, the long-term durability of these improvements is uncertain, with variability in cartilage repair quality and functional outcomes, indicating a need for more rigorous studies to assess its long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Mithoefer, K., McAdams, T., Williams, RJ., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01656902

NCT01656902 | Phase III Study to Evaluate Safety and ... The investigated study treatment NOVOCART 3D plus is a biphasic biological scaffold which contains cultivated chondrocytes derived from the patient in a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12344510/

A non‐interventional study to evaluate the safety and ... The focus of this study was to evaluate the safety and efficacy of NOVOCART® 3D‐treatment over a period of 36 months post‐transplantation.

3. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2011-005798-22/results

EudraCT Number 2011-005798-22 - Clinical trial results A clinical study to evaluate the safety and effectiveness of NOVOCART® 3D plus compared to microfracture in the treatment of articular cartilage defects of the ...

4. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2022/01/13181-Autologous-Chondrocyte-Implant-for-Articular-Cartilage-Defects-V1.0-SEP2019-NON-CONF.pdf

NOVOCART 3D for articular cartilage defects of the knee Phase III Study to Evaluate Safety and Effectiveness of NOVOCART 3D Plus vs. Microfracture in Knee Cartilage Defects (N3D). Trial ID: NCT01656902. Available ...

5. trial.medpath.com trial.medpath.com/clinical-trial/46a233f3f8f0829d/euctr2011-005798-22-lv-clinical-study-novocart-3d-plus-knee-cartilage-defects

A clinical study to evaluate the safety and effectiveness of ... A clinical study to evaluate the safety and effectiveness of NOVOCART® 3D plus compared to the standard of care (microfracture) in the treatment of cartilage ...