Phase III Study to Evaluate Safety and Effectiveness of NOVOCART 3D Plus vs. Microfracture in Knee Cartilage Defects

NCT01656902 | Completed Phase 3 DMC

• 1 other identifier: AAG-G-H-1202
• Study Type: interventional
• Target: 263
• Locations: 10 countries
• Sites: 35

Brief Summary

In this phase 3 clinical trial, a second generation ACI (autologous chondrocyte implantation technique) is compared to standard of care therapy (microfracture) to treat traumatic cartilage defects of the knee for efficacy and safety. The investigated study treatment NOVOCART 3D plus is a biphasic biological scaffold which contains cultivated chondrocytes derived from the patient in a previous tissue harvest procedure. Allocation to the study treatment is done by randomization in a ration of 2:1 in favor to ACI (investigational product). Follow-up data for efficacy is collected for 2 years: follow-up visits are performed 6 weeks, 3 months, 6 months, 12 months, 18 months and 24 months after treatment; additional data for safety will be collected for up to 5 years: 36, 48, and 60 months after treatment. The study involves knee surgery (by arthroscopy, or mini-arthrotomically for implantation surgery), and blood withdrawal for safety within the first year after treatment. Initial imaging is required at baseline. Optional MRI imaging and biomarker collection is done as substudy at specific sites only.

Conditions

Traumatic Articular Cartilage Defects in the Knee Joint

Keywords

Autologous Chondrocyte Transplantation; NOVOCART 3D plus; knee joint pain; safety; efficacy; treatment; TETEC; cartilage; ACT; cartilage repair; tissue; MOCART

Outcome Measures

Primary Outcomes (1)

• Subjective IKDC score

  The primary endpoint is the change from baseline in the "2000 International Knee Documentation Committee" (IKDC) subjective score to 24-month visit. The IKDC will be recorded for NOVOCART® 3D plus and microfracture patients at baseline visit 1 and at the 6 weeks, 3-, 6-, 12-, 24-, 36-, 48,- and 60-month follow-up assessments.

  Baseline assessment to 24-month follow-up assessment

Secondary Outcomes (8)

• IKDC objective physician score

  Baseline assessment to 24-month follow-up assessment

• Knee Injury and Osteoarthritis Outcome Score (KOOS)

  Baseline assessment to 24-month follow-up assessment

• MOCART Score (MRI)

  Baseline assessment to the 24-month assessment

• Health-related quality of life as measured by the SF-36 survey

  Baseline assessment to 24-month follow-up assessment

• Surgical time (cut-to-suture time)

  Transplantation (24 +-5 days post-arthroscopy) and/or arthroscopy (>= 1 day after screening), depending on the study arm

Study Arms (2)

N3D plus

EXPERIMENTAL

NOVOCART® 3D plus (Autologous Chondrocyte Transplantation System)

Drug: NOVOCART® 3D plus

Microfracture

ACTIVE COMPARATOR

Microfracture is the standard care surgery.

Procedure: Microfracture

Interventions

NOVOCART® 3D plus DRUG

Two-Step intervention: 1) cartilage cells are collected from the patient during arthroscopy 2) collected cartilage cells are cultivated in a sterile environment, seeded in an organic matrix scaffold and implanted into the defect location (knee, femur)

Also known as: Matrix-associated autologous chondrocyte implantation

N3D plus

Microfracture PROCEDURE

single-step treatment: defect location (knee, femur) is debrided, then bone plate is drilled mechanically to allow cells from the bone marrow to move to the defect location and to develop a scar tissue

Also known as: Microfracture according to Steadman

Microfracture

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is between 18 and 65 years old at screening OR (in selected countries only) is a pediatric patient (14-17 years old) with closed epiphyseal growth plate (confirmation of closure of epiphyseal growth plate of the index knee by x-ray or MRI required).
• Patient has a localized articular cartilage defect of the femoral condyle or the trochlea of the knee. 2 localized cartilage defects are accepted if the total defect size is ≤ 6 cm2 and the size of each individual lesion is ≥ 2 cm2, both cartilage defects are located at the femoral condyle and/or the trochlea and both cartilage defects are to be treated with NOVOCART 3D plus or microfracture.
• Patient has a defect size is between 2 and 6 cm2. Note: defect size can be estimated by MRI at visit 1 if no data is available from medical history.
• Patient has an intact articulating joint surface (not higher than Grade 2 International Cartilage Repair Society classification, no kissing lesions). Note: ICRS classification can be estimated by MRI at visit 1 if no data is available from medical history.
• Patient has an intact meniscus; a maximum of 50% resection is allowed. Note: status of meniscus can be estimated at visit 1 if no data is available from medical history.
• Patient has a stable knee joint or sufficiently reconstructed ligaments. If not, ligament repair must be done before, during or within 6 weeks after cartilage treatment (ACT/microfracture).
• Patient has free range of motion of the affected knee joint or ≤ 10° of extension and flexion loss.
• Patient has a defect-grade of III or IV according to the ICRS classification. Note: ICRS classification can be estimated by MRI at visit 1 if not data is available from medical history.
• Patient has a baseline score of 60/100 on the 2000 International Knee Documentation Committee (IKDC) subjective knee evaluation.
• Patient is willing and able to give written informed consent to participate in the study and to comply with all study requirements, including attending all follow-up visits and assessments and postoperative rehabilitation regimen.
• Mandatory for France only: Patient benefits of a health insurance regimen.

You may not qualify if:

• Patient is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.
• Patient is unable to undergo magnetic resonance imaging (MRI).
• Patient has prior surgical treatment of the target knee using mosaicplasty, autologous chondrocyte transplantation and/or microfracture. Note: prior diagnostic arthroscopies with debridement and lavage are acceptable. Ligament repair is accepted, if performed before, during or within 6 weeks after cartilage treatment (ACT/microfracture).
• Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade \> 2 (see Appendix A).
• Patient has chronic inflammatory arthritis and/or infectious arthritis.
• Patient has joint space narrowing \> 1/3 in the target knee when compared to the other knee or smaller than 3 mm joint space measured on x-ray.
• Patient has malalignment (valgus- or varus-deformity) in the target knee. Note: In suspected cases, the mechanical axis must be established radiographically by complete leg imaging in standing position and in a.p. or rather p.a. projection. The Mikulicz line is not allowed to deviate more than 5 mm of the eminentia intercondylaris. If alignment is necessary, surgery has to be performed before, during or within 6 weeks after cartilage treatment (ACT/microfracture).
• Patient has prior surgical treatment of clinical relevance of the target knee.
• Patient has an osteochondral defect.
• Patient has bilateral lower limb pain or low back pain.
• Patient has a known systemic connective tissue disease.
• Patient has a current uncontrolled diabetes.
• Patient has a known history of autoimmune disease.
• Patient has a known history of immunological suppressive disorder or is taking immunosuppressants.
• Patient is currently systemically or intra-articularly taking steroids and/or has used steroids within the last 30 days prior to screening visit 1.

Sponsors & Collaborators

• Tetec AG: lead

Study Sites (35)

Privatklinik Doebling

Vienna, 1190, Austria

Location

Fakultni nemocnice Brno - Ortopedicka klinika

Brno, 62500, Czechia

Location

Urazova nemocnice v Brne - Traumatologie

Brno, 66250, Czechia

Location

NH Hospital, a.s., Ortopedicke oddeleni nemocnice Horovice

Hořovice, 26831, Czechia

Location

Fakultni nemocnice Hradec Kralove - Ortopedicka klinika

Hradec Králové, 50005, Czechia

Location

Pardubicka nemocnice

Pardubice, 53203, Czechia

Location

Fakultni nemocnice v Motole

Prague, 15006, Czechia

Location

UVN - Vojenska fakultni nemocnice Praha

Prague, 16902, Czechia

Location

Hôpital Ambroise Paré - Service de Chirurgie Orthopedique et Traumatologie

Boulogne-Billancourt, 92104, France

Location

Polyclinique Saint-Roch

Montpellier, 34075, France

Location

Clinique V - Clinique du Sport

Paris, 75005, France

Location

CHU de Saint-Etienne Hôpital Nord - Service orthopedie et traumatologie

Saint-Priest-en-Jarez, 42270, France

Location

Universitaetsklinikum Freiburg - Klinik fuer Orthopaedie

Freiburg im Breisgau, 79106, Germany

Location

Theresienkrankenhaus

Mannheim, 68165, Germany

Location

Orthopädische Klinik und Poliklinik der LMU München

München, 81377, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93042, Germany

Location

Uzsoki utcai Kórház

Budapest, 1145, Hungary

Location

Petz Aladár Megyei Oktató Kórház

Győr, 9024, Hungary

Location

B-A-Z Megyei Központi Kórház és Egyetemi Oktatókórház

Miskolc, 3526, Hungary

Location

Markusovszky Egyetemi Oktatókórház

Szombathely, 9700, Hungary

Location

Kastélypark Klinika

Tata, 2890, Hungary

Location

Hospital of Traumatology and Orthopaedics, Trauma Department

Riga, 1005, Latvia

Location

Orto Clinic

Riga, 1005, Latvia

Location

Kaunas clinical hospital

Kaunas, 44320, Lithuania

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, 50009, Lithuania

Location

Klaipeda university hospital

Klaipėda, 92288, Lithuania

Location

JSC "Kardiolita"

Vilnius, 05263, Lithuania

Location

JSC "SK Impeks Medicinos Diagnostikos Centras"

Vilnius, 10318, Lithuania

Location

Szpital sw. Lukasza BGL Sp z o.o. S.K.A.

Bielsko-Biala, 43309, Poland

Location

Samozdzielny Publiczny Zaklad Opieki Zdrowotnej Miejskiego Szpitala Zespolonego

Częstochowa, 42200, Poland

Location

Szpital Angelius

Katowice, 40611, Poland

Location

Samozdzielny Publiczny Wojewodzki Szpital Chirurgii Urazowej

Piekary Śląskie, 41940, Poland

Location

Centrum Medycyny Sportowej

Warsaw, 02034, Poland

Location

Universitätsklinikum Basel

Basel, 4031, Switzerland

Location

Royal Devon and Exeter Hospital

Exeter, EX2 5DW, United Kingdom

Location

MeSH Terms

Interventions

Arthroplasty, Subchondral

Intervention Hierarchy (Ancestors)

Arthroplasty; Orthopedic Procedures; Surgical Procedures, Operative; Plastic Surgery Procedures

Study Officials

• Peter Angele, Prof.

  Universitätsklinikum Regensburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2012
• First Posted: August 3, 2012
• Study Start: May 1, 2013
• Primary Completion: March 6, 2020
• Study Completion: February 28, 2023
• Last Updated: November 24, 2023

Record last verified: 2021-10

Locations

LI (5); CZ (7); HU (5); GB (1); FR (4); DE (4); CH (1); LA (2); PL (5); AU (1)