Clinical Trial for the Regeneration of Cartilage Lesions in the Knee

NCT02673905 | Completed

• 1 other identifier: NosetoKnee2
• Study Type: interventional
• Target: 108
• Locations: 4 countries
• Sites: 5

Brief Summary

The purpose of this study is to investigate the efficacy of an engineered cartilage transplant (N-TEC) in comparison to a cell-activated matrix (N-CAM) for the treatment of articular cartilage lesions in the knee. The main innovations in this trial are the use of nasal chondrocytes and the implantation of a tissue in contrast to cells seeded on a matrix. The goals of the trial are to: (i) evaluate whether implantation of a more mature graft (tissue therapy) is beneficial for the quality and durability of the repair tissue and the clinical outcome, (ii)determine the potential of the mature graft to integrate with the adjacent cartilage and form hyaline repair tissue and (iii) assess the efficacy of each treatment in correlation to the characteristics of the defect (e.g. "acute" versus "chronic" setting).

Conditions

Tear; Knee, Cartilage, Articular

Keywords

nasal chondrocytes; articular chondral lesions; tissue engineering; femoral condyle; trochlea

Outcome Measures

Primary Outcomes (1)

• comparison of the efficacy of the two investigational medicinal products (IMPs)

  Assessment whether a tissue therapy will improve the clinical efficacy for the patient, leading to an increase of at least 10 points in the main primary outcome (self-assessed score KOOS) after 24 months as compared to the cell therapy group

  24 months

Secondary Outcomes (2)

• stability and Integration of the implanted IMP

  24 months

• efficacy for patient

  24 months

Other Outcomes (2)

• efficacy of IMPs related to acute vs. chronic lesions

  24 months

• safety of IMPs

  24 months

Study Arms (2)

N-TEC (tissue engineered product)

EXPERIMENTAL

N-TEC is based on autologous nasal chondrocytes expanded and further cultured on type I/III collagen membrane for 2 weeks to allow the cells to produce extracellular matrix containing cartilage specific Proteins. The IMP is implanted in the knee joint and secured by sutures.

Other: Tissue Engineered Product

N-CAM (tissue engineered product)

EXPERIMENTAL

N-Cell activated Matrix (CAM) is based on autologous nasal chondrocytes expanded and further cultured on type I/III collagen membrane for 2 days only to allow the cells to adhere. The IMP is implanted in the knee joint and secured by sutures.

Other: Tissue Engineered Product

Interventions

Tissue Engineered Product OTHER

Implantation of tissue engineered products

Also known as: N-TEC (tissue), N-CAM (Cell activated matrix)

N-CAM (tissue engineered product); N-TEC (tissue engineered product)

Eligibility Criteria

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

You may qualify if:

• Patient is ≥18 and ≤65 years old at time of screening.
• Patient has a localized articular cartilage defect of the femoral condyle and/or the trochlea of the knee. 2 localized cartilage defects are accepted if the total defect size is ≤ 8 cm2, both cartilage defects are located at the femoral condyle and/or the trochlea and both cartilage defects are to be treated with N-CAM or N-TEC.
• Patient has a defect of grade 3 or 4 according to the ICRS classification.
• Patient has a defect size ≥2 and ≤8 cm2 as assessed by MRI/arthroscopy.
• Patient has an intact (≤ICRS Grade 2 ) articulating joint surface (no "kissing lesions").
• Patient has an intact meniscus (maximum 1/2-resection).
• Patient has a stable knee joint or sufficiently reconstructed ligaments. If not, ligament repair has to be done during the operation or within 6 weeks of the planned cartilage treatment.
• Patient has a maximum baseline score of 75/100 in the KOOS 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 to complete postoperative rehabilitation regimen.

You may not qualify if:

• Patient is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol or in a dependency or employment with the sponsor.
• Patient is unable to understand the patient information
• Patient is unable to undergo magnetic resonance imaging (MRI) or is sensitive to gadolinium
• Patient has had prior surgical treatment of the target knee within 12 months using mosaicplasty and/or microfracture (Note: prior diagnostic arthroscopy with debridement and lavage are acceptable within 12 months). Anterior cruciate ligament repair is accepted, if the target knee is stable or a primary Anterior cruciate ligament (ACL) reconstruction is performed within 6 weeks of the planned cartilage treatment.
• Patient has a relevant meniscus tear. Partial meniscal removal allowed, if not exceeding 1/2. Meniscus suture is not allowed in parallel, but if successful, cartilage treatment might be added 12 months later.
• Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade \>2.
• Patient has chronic inflammatory arthritis, and/or infectious arthritis.
• Patient has an unstable knee joint or insufficiently reconstructed ligaments. If ligament repair is necessary, the repair has to be performed during the operation or within 6 weeks of the planned cartilage treatment.
• Patient has malalignment (no valgus- or varus-deformity) in the target knee ≥ 5°. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in a.p. or rather p.a. projection. If alignment surgery is necessary, surgery has to be performed within 6 weeks of the planned cartilage treatment.
• Patient has an osteochondral defect (defined as bony substance defect of \>3mm depth). Bone marrow edema is allowed.
• Patient has relevant bilateral lower limb pain.
• Patient has a known systemic connective tissue disease.
• Patient has a known autoimmune disease.
• Patient has a known immunological suppressive disorder or is taking immunosuppressives.
• Patient is currently systemically or intra-articularly taking steroids and/or has used steroids within the 30 days prior to the planned treatment.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• University Hospital Freiburg: collaborator
• I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio: collaborator
• General Hospital Sveti Duh: collaborator
• Fraunhofer-Institut für Silicatforschung ISC: collaborator
• Orthopaedische Klinik Koenig-Ludwig-Haus: collaborator

Study Sites (5)

University Hospital Sveti Duh

Zagreb, 10000, Croatia

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Orthopädische Klinik König-Ludwig-Haus

Würzburg, 97074, Germany

Location

Istituto Ortopedico Galeazzi (IOG)

Milan, 20161, Italy

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (1)

• Mumme M, Wixmerten A, Ivkovic A, Peretti GM, Yilmaz T, Reppenhagen S, Pullig O, Miot S, Izadpanah K, Jakob M, Mangiavini L, Sosio C, Vuletic F, Bieri O, Biguzzi S, Gahl B, Lehoczky G, Vukojevic R, Hausner S, Gryadunova A, Haug M, Barbero A, Martin I. Clinical relevance of engineered cartilage maturation in a randomized multicenter trial for articular cartilage repair. Sci Transl Med. 2025 Mar 5;17(788):eads0848. doi: 10.1126/scitranslmed.ads0848. Epub 2025 Mar 5.

  PMID: 40043142 RESULT

MeSH Terms

Conditions

Lacerations

Interventions

Histocompatibility Testing

Condition Hierarchy (Ancestors)

Wounds and Injuries

Intervention Hierarchy (Ancestors)

Immunologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Immunologic Techniques

Study Officials

• Marcel Jakob, Prof. Dr.

  University Hospital, Basel, Switzerland

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: February 4, 2016
• Study Start: November 1, 2016
• Primary Completion: November 15, 2022
• Study Completion: November 15, 2022
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1); IT (1); CH (1); DE (2)