NOVOCART 3D vs Microfracture for Knee Cartilage Defects

(N3D Trial)

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

233 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment NOVOCART 3D vs Microfracture for Knee Cartilage Defects?

Research shows that microfracture is a common treatment for knee cartilage injuries, but its long-term effectiveness is not well-documented. Comparisons with other treatments like NeoCart suggest that alternatives may offer benefits, but more specific data on NOVOCART 3D is needed. ^{1 2 3 4 5}

Is the NOVOCART 3D treatment safe for humans?

The NeoCart implant, similar to NOVOCART 3D, was found to be safe in early clinical trials for knee cartilage injuries. Microfracture surgery, a standard treatment for knee cartilage defects, is generally safe, with most patients experiencing improved knee function, although some may have postoperative stiffness. ^{2 4 6 7 8}

How does the NOVOCART 3D treatment for knee cartilage defects differ from other treatments?

NOVOCART 3D is a unique treatment for knee cartilage defects as it involves a tissue-engineered bioimplant designed to repair articular cartilage, offering a novel approach compared to the traditional microfracture technique, which is a standard surgical method that creates small fractures in the bone to stimulate cartilage growth. ^{1 2 4 6 9}

What is the purpose of this trial?

This trial compares two methods for treating damaged knee cartilage. It aims to see which method better reduces pain and improves knee function. The study will monitor patients over several years to evaluate safety and effectiveness.

Research Team

Robert Spiro, PhD

Principal Investigator

Octane Biotherapeutics, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. [2022]

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

Microfracture Versus Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Knee: A Systematic Review of 5-Year Outcomes. [2022]

3. Germany 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. [2021]

4. United States 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. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Microfracture for cartilage repair in the knee: a systematic review of the contemporary literature. [2021]

6. United States 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. [2019]

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

Can Biologic Augmentation Improve Clinical Outcomes Following Microfracture for Symptomatic Cartilage Defects of the Knee? A Systematic Review. [2019]

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

Microfracture: indications, technique, and results. [2022]

9. United States 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. [2019]