MACI vs Microfracture for Knee Cartilage Injury

(PEAK Trial)

Recruiting at 10 trial locations

Overseen By Kristin M Tripp, BS

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Vericel Corporation

Disqualifiers: Rheumatoid arthritis, Metabolic bone disease, Psoriasis, 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: 2

Duration: 1-time procedure within 12 weeks of screening

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two treatments, MACI® and microfracture, for repairing knee cartilage injuries in young people. MACI® (Matrix-induced Autologous Chondrocyte Implantation) uses a special membrane with the patient's own cells, while microfracture employs a surgical technique to aid knee healing. The trial targets children and teens with painful knee cartilage issues that have not healed naturally. Suitable candidates have knee injuries impacting daily activities but have not undergone knee surgery in the past six months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the development of a potentially groundbreaking treatment.

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 MACI is a safe choice for repairing knee cartilage. A two-year study found that MACI is effective and safe, with straightforward methods leading to significant improvements. Other research supports this, indicating that unwanted side effects were rare.

Microfracture, the other treatment in this trial, is a surgical method used for many years to treat knee cartilage damage and has a good safety record.

Studies have shown that both treatments are well-tolerated, suggesting they are safe options for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MACI, a treatment for knee cartilage injuries, because it uses autologous cultured chondrocytes on a porcine collagen membrane. This method is unique as it involves using the patient's own cells to repair damaged cartilage, potentially leading to better integration and more natural healing compared to traditional methods like microfracture surgery. Unlike microfracture, which relies on creating small fractures in the bone to stimulate cartilage growth, MACI directly implants cultured cells, offering a more targeted and potentially more effective approach to cartilage repair.

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

This trial will compare MACI, a treatment using a patient's own cells to repair knee cartilage, with microfracture, a common surgery for knee issues. Research has shown that MACI is safe and effective. In the SUMMIT trial, MACI outperformed microfracture, with about 74% of patients rating their knee as "good" or "excellent" after successful MACI treatments, and 70% expressing satisfaction with their surgery. Although microfracture is a standard method, it does not perform as well in the long term as MACI. Overall, MACI typically provides more lasting and satisfying results for knee cartilage repair. ^{1 2 3 6 7}

Who Is on the Research Team?

Jonathan Hopper

Principal Investigator

Vericel Corporation

Are You a Good Fit for This Trial?

This trial is for young people aged 10-17 with knee problems like cartilage damage or osteochondritis. They should have a specific type of severe cartilage injury that can be treated surgically, and their knee must be stable. It's not for those who've had recent surgery on the same knee, are pregnant, have certain allergies, or joint conditions like rheumatoid arthritis.

Inclusion Criteria

My knee's crucial ligaments are stable, possibly after surgery.

I have a knee injury larger than 1.5 cm2 but no deeper than 6 mm.

I have painful joint or bone cartilage damage.

Exclusion Criteria

I haven't had surgery on my knee, except for a diagnostic look, in the last 6 months.

I have a condition like arthritis or psoriasis that affects my joints.

I have severe knee cartilage damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 12 weeks

1 visit (in-person) for screening arthroscopy

Treatment

Participants receive either MACI or microfracture treatment

1-time procedure within 12 weeks of screening

1 visit (in-person) for treatment

Rehabilitation

Participants follow a recommended postoperative rehabilitation program

12 weeks

Regular monitoring for compliance

Follow-up

Participants are monitored for safety and effectiveness after treatment

104 weeks

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• MACI
• Microfracture

Trial Overview The study compares two treatments for serious knee cartilage injuries in youth: MACI (a cell-based implant) and microfracture (a surgical technique). The goal is to see which one is safer and works better at repairing the damaged areas in the knees of these patients.

How Is the Trial Designed?

Group I: MACI Experimental Treatment 1 Intervention

autologous cultured chondrocytes on porcine collagen membrane

Group II: microfracture Active Control 1 Intervention

surgical procedure

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

Approved in United States as MACI for:

• Symptomatic articular cartilage defects of the knee

Approved in European Union as MACI for:

• Symptomatic articular cartilage defects of the knee

Who Is Running the Clinical Trial?

Vericel Corporation

Lead Sponsor

Trials

14

Recruited

3,100+

Published Research Related to This Trial

In a randomized controlled trial involving 144 patients, the 5-year follow-up showed that autologous cultured chondrocytes on porcine collagen membrane (MACI) significantly improved pain and function in patients with knee cartilage defects compared to microfracture treatment.

The study found no major safety concerns with MACI, indicating it is a reliable treatment option for symptomatic cartilage defects, with improvements in daily activities and quality of life maintained over the 5-year period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Five-Year Follow-up of a Prospective Randomized Trial. Brittberg, M., Recker, D., Ilgenfritz, J., et al.[2022]

In a study of 27 patients undergoing matrix-guided autologous chondrocyte implantation (MACI) for knee cartilage defects, MRI results showed that MACI led to a significant increase in defect filling from 40% at 6 months to 85% at 2 years, with complete remission observed in 17 out of 27 cases.

In comparison, microfracture (MFX) treatment resulted in less effective cartilage regeneration, with only 2 out of 7 patients achieving complete remission, highlighting that MACI is superior to MFX in both the rate of complete remissions and the quality of cartilage repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[MRI in the follow-up of matrix-supported autologous chondrocyte transplantation (MACI) and microfracture]. Bachmann, G., Basad, E., Lommel, D., et al.[2022]

In a study of 41 patients with knee cartilage defects, matrix-induced autologous chondrocyte implantation (MACI) showed significant improvements in clinical outcomes and MRI scores over a 5-year period, indicating its efficacy as a treatment option.

At 5 years post-surgery, 67% of MACI grafts achieved complete infill of cartilage defects, and 98% of patients reported satisfaction with pain relief, suggesting that MACI can effectively enhance quality of life for patients with knee issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and magnetic resonance imaging-based outcomes to 5 years after matrix-induced autologous chondrocyte implantation to address articular cartilage defects in the knee. Ebert, JR., Robertson, WB., Woodhouse, J., et al.[2019]

In a study of 30 patients who underwent matrix-induced autologous chondrocyte implantation (MACI), the histological quality of the repaired knee cartilage was assessed, revealing that only 30% of biopsies were classified as normal, indicating that many repairs may still be maturing.

The study found no significant correlation between the macroscopic appearance of the repair tissue and the actual histological quality or the patients' functional status, suggesting that visual assessments may not accurately reflect the true state of cartilage repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matrix-induced autologous chondrocyte implantation (MACI) in the knee. Enea, D., Cecconi, S., Busilacchi, A., et al.[2021]

Arthroscopic matrix-induced autologous chondrocyte implantation (MACI) leads to better recovery outcomes compared to traditional open arthrotomy, with significant improvements in knee range of motion and functional tests over 12 months in 78 patients.

Patients undergoing arthroscopic MACI experienced shorter hospital stays and fewer postoperative complications, suggesting this technique may facilitate faster rehabilitation and a quicker return to full function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arthroscopic versus open matrix-induced autologous chondrocyte implantation: results and implications for rehabilitation. Edwards, PK., Ebert, JR., Janes, GC., et al.[2019]

Matrix-applied autologous chondrocyte implantation (MACI) is a newly approved technique for treating large cartilage defects in the knee, utilizing cultured chondrocytes on a porcine collagen membrane, which simplifies the procedure and improves cell seeding reliability.

Patients undergoing MACI show significant improvements in knee function and symptoms, with better outcomes reported up to 5 years post-surgery compared to those treated with traditional microfracture techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open Implantation of Autologous Chondrocytes Cultured on Porcine Collagen Membrane for the Treatment of a Full-Thickness Patellar Cartilage Lesion. Schmiesing, AM., Ridley, TJ., Macalena, JA.[2020]

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]

A study involving 1000 adult patients treated with MACI (autologous cultured chondrocytes on porcine collagen membrane) for knee cartilage repair showed that the majority had a single defect, with an average defect size of 4.7 cm², and a low adverse event rate of only 2.6%.

The patient demographics and defect characteristics in this U.S. study were consistent with previous European trials, indicating that MACI is a viable treatment option for knee cartilage defects, particularly as treatment of multiple defects is more common in the U.S.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of MACI (Autologous Cultured Chondrocytes on Porcine Collagen Membrane) in the United States: Preliminary Experience. Carey, JL., Remmers, AE., Flanigan, DC.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4266264/

Matrix-induced autologous chondrocyte implantation for ... This 2-year study has confirmed that MACI is safe and effective with the advantages of a simple technique and significant clinical improvements.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2667254523000045

MACI (autologous cultured chondrocytes on porcine ... Of those with intact MACI grafts, 17 out of 23 (74%) rated their knee as “good” or “excellent” and 16 out of 23 (70%) were satisfied with their surgery.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11982059/

Use of MACI (Autologous Cultured Chondrocytes on ... The FDA approval of MACI was supported by the results of the European SUMMIT (Superiority of MACI Implant Versus Microfracture Treatment) trial— ...

4. maci.com maci.com/pdf/2%20Year%20SUMMIT%20Trial%20-%20Reprint%20Carrier.pdf

Matrix-Applied Characterized Autologous Cultured ... Conclusion: The treatment of symptomatic cartilage knee defects 3 cm2 in size using MACI was clinically and statistically signifi- cantly better than with MFX, ...

5. maci.com maci.com/patients/

MACI (autologous cultured chondrocytes on porcine collagen ... A MACI specialist will repair your knee cartilage by using your own cells to create durable repair tissue that may reduce pain.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2212628723003560

All-Arthroscopic Matrix-Associated Autologous ... In this technique article, MACI (autologous cultured chondrocytes on porcine collagen membrane) is used to treat a femoral trochlear defect of the knee.

7. researchgate.net researchgate.net/publication/6436700_Matrix-Induced_Autologous_Chondrocyte_Implantation_MACI_R_Biological_and_Histological_Assessment

Matrix-Induced Autologous Chondrocyte Implantation ... Our data showed that chondrocytes on the collagen scaffold appeared spherical, well integrated into the matrix, and maintained the chondrocyte ...