NOVOCART® Inject Plus for Cartilage Defects of the Knee

NCT03319797 | Completed Phase 3 DMC

• 1 other identifier: AAG-G-H-1624
• Study Type: interventional
• Target: 100
• Locations: 5 countries
• Sites: 20

Brief Summary

Prospective, Multicenter, Single-arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of NOVOCART® Inject plus in the Treatment of Cartilage Defects of the Knee. The primary objective of this trial is to demonstrate efficacy of NOVOCART® Inject plus for the treatment of cartilage defects of the knee based on the Knee injury and Osteoarthritis Outcome Score (KOOS) responder rate 24 month after transplantation.

Conditions

Cartilage Defects of the Knee

Keywords

Autologous chondrocyte transplantation ACT

Outcome Measures

Primary Outcomes (1)

• Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5). The KOOS score ranges from 0 to 100 (100 indicating no symptoms and 0 indicating extreme symptoms).

  Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5) defined as the average of the 5 subscale scores (ensuring identical weight from all subscales) at the 24 months follow-up assessment. The KOOS5 responder rate is defined as the proportion of patients with ≥ 10 points improvement in the KOOS5 from baseline to the 24 months visit.

  24 month

Secondary Outcomes (12)

• Change in the KOOS5

  24 month

• Change in the 5 individual subscores of the KOOS

  24 month

• Change in the International Knee Documentation Committee (IKDC) subjective score. The IKDC score ranges from 0 to 100, with 100 indicating the absence of symptoms and higher levels of functioning.

  24 month

• Change in EQ-5D-5L. The components are the EQ-5D-5L index ranging from <0 (worse than dead) to 1 (full health) and a visual analogue scale with the end points of 0 (worst health) and 100 (best health).

  24 month

• Change in activity level/ functional status. Patient questionnaire on activity (sporting habits) and functional status (degree of restriction in general), no score provided.

  24 months

Study Arms (1)

Treatment with NOVOCART® Inject plus

OTHER

Treatment with NOVOCART® Inject plus (Autologous chondrocyte transplantation)

Drug: NOVOCART® Inject plus

Interventions

NOVOCART® Inject plus DRUG

Treatment with NOVOCART® Inject plus (Autologous chondrocyte implantation)

Treatment with NOVOCART® Inject plus

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 ≥ 18 and ≤ 65 years old at screening. Pediatric patients (14 to 17 years) with closed epiphysis may be included in selected countries. Closure of the distal femoral epiphysis of the target knee needs to be confirmed by MRI or x-ray.
• Patients with focal articular cartilage defect(s) of the femoral condyle (medial or lateral), the trochlea, the patella or the tibial plateau (medial or lateral) of the knee.
• Patient has one or two defects in the target knee with a defect-grade of III or IV according to the International Cartilage Repair Society (ICRS) classification or grade III or IV ICRS classification of osteochondritis dissecans lesions (ICRS-OCD).
• If the patient has only one grade III or IV defect, the size of the defect is ≥ 4 and ≤ 12 cm2 post debridement. If the patient has two grade III or IV cartilage defects the total defect size is ≥ 4 and ≤ 12 cm2 post debridement. The defects must be located on different, knee joint areas and both cartilage defects are to be treated with NOVOCART® Inject plus.
• Patient has an intact, well contained chondral structure surrounding the defect (i.e. no diffusely thinned-out cartilage surface) and an articulating joint surface opposite to the defect(s) to be treated (≤ Grade I ICRS or ICRS-OCD classification).
• Patient has intact menisci in the target knee; a maximum of 50% resection per meniscus is allowed. Completely healed meniscal transplants are accepted.
• Patient has a stable knee joint or sufficiently reconstructed ligaments and no patella malalignment or a sufficiently corrected patella malalignment. Ligament repair is accepted, if performed before, during or within 6 weeks after NOVOCART® Inject plus transplantation. Correction of patella malalignment must be performed before or during NOVOCART® Inject plus transplantation.
• Patient has free range of motion (ROM) of the affected knee joint or ≤ 10° of active extension and flexion loss (compared to the other knee).
• Patient has a baseline score of \< 65/100 in the overall KOOS (KOOS5).
• Only for female patients of childbearing potential (sexually mature, pre-menopausal and not surgically sterile): the patient is willing to use a medically accepted method of contraception until the day of NOVOCART® Inject plus transplantation.
• Patient is willing and able to give written informed consent to participate in the study and to comply with all follow-up visits and assessments and the postoperative rehabilitation program.
• Patient is not pregnant as confirmed by urine pregnancy test before arthroscopy
• Patients with focal articular cartilage defect(s) of the femoral condyle (medial or lateral), the trochlea, the patella or the tibial plateau (medial or lateral) of the knee.
• Patient has one or two defects in the target knee with a defect-grade of III or IV according to the International Cartilage Repair Society (ICRS) classification or grade III or IV ICRS classification of osteochondritis dissecans lesions (ICRS-OCD).
• If the patient has only one grade III or IV defect, the size of the defect is ≥ 4 and ≤ 12 cm2 post debridement. If the patient has two grade III or IV cartilage defects the total defect size is ≥ 4 and ≤ 12 cm2 post debridement. The defects must be located on different knee joint areas and both cartilage defects are to be treated with NOVOCART® Inject plus.

You may not qualify if:

• Patient is unable to undergo magnetic resonance imaging (MRI).
• Patient has grade II cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
• Patient has more than 2 grade III or IV cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
• The cartilage defects (ICRS or ICRS-OCD grade I or III or IV) affect more than 3 out of 6 joint areas1 of the target knee.
• Patient had a prior biologic reconstructive procedure (e.g. microfracture, mosaicplasty, chondrocyte transplantation) in the target knee at a location different from the defect location to be treated in the study. Prior biologic reconstructive procedures are accepted, if the previously treated defect is the same defect that is planned to be treated with NOVOCART® Inject plus (i.e. the prior method has failed) and these procedures were performed ≥ 24 months prior to screening visit 1.
• Patient had other prior surgical interventions interfering with the assessment of the NOVOCART® Inject plus treatment. Prior diagnostic arthroscopies with debridement and lavage are acceptable.
• Patients with subchondral bone defects more than 2 mm deep (after resection of affected bone) unless adjuvant defect filling will be performed before or during NOVOCART® Inject plus transplantation.
• Patient has 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 joint space narrowing \> 1/3 in the target knee when compared to the other knee or \< 3 mm joint space.
• 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 anteriorposterior (a.p.) or rather posterioranterior (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 NOVOCART® Inject plus transplantation.
• Patient has arthrofibrosis in the target knee.
• Patient has diffuse chondromalacia (grade 1 'softening or swelling of cartilage' according to Outerbridge allowed).
• Patient has metabolic arthropathies (e.g. gout, pseudo-gout)
• Patient has bilateral lower limb pain or low back pain.

Sponsors & Collaborators

• Tetec AG: lead

Study Sites (20)

Orthopedic department of Hospital of Rudolf and Stefanie Benešov

Benešov, 25601, Czechia

Location

Clinic of traumatology Úrazová nemocnice Brno

Brno, 66250, Czechia

Location

NH Hospital, a.s., Department of Orthopaedics, Hořovice Hospital

Hořovice, 268 31, Czechia

Location

Orthopaedic Department of Faculty Hospital Ostrava

Ostrava, 70852, Czechia

Location

Orthopaedic department of Hospital pardubice, Hospital of Pardubice Region

Pardubice, 530 03, Czechia

Location

Clinic of child and adult orthopaedics and traumatology 2nd Medical faculty Charles University and FH Motol

Prague, 15006, Czechia

Location

University Hospital Freiburg, Department for Orthopaedics and Trauma Surgery

Freiburg im Breisgau, 79106, Germany

Location

Orthodoc MVZ orthopaedics and surgery at medical center Sophienhof GmbH

Kiel, 24103, Germany

Location

Orthopaedic Surgery Munich

Munich, 81369, Germany

Location

Uzsoki Hospital

Budapest, 1145, Hungary

Location

Szabolcs-Szatmár-Bereg County Hospitals and University Teaching Hospital, Jósa András Teaching Hospital

Nyíregyháza, 4400, Hungary

Location

Bács-Kiskun County Hospital, Teaching Hospital of Faculty of Medicine of University of Szeged

Szeged, 6725, Hungary

Location

Szegedi Tudományegyetem Ortopédiai Klinika

Szeged, 6725, Hungary

Location

Jász-Nagykun-Szolnok County Hetényi Géza Hospital - Clinic, Traumatology

Szolnok, 5000, Hungary

Location

Kastélypark Clinic

Tata, 2890, Hungary

Location

"Ortopedijos technika", PLC

Kaunas, 49476, Lithuania

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, 50161, Lithuania

Location

Klaipeda university hospital

Klaipėda, 92288, Lithuania

Location

Orthopedics "at Rhy"

Basel, 4056, Switzerland

Location

Centrum for orthopedics & sports

Zurich, 8047, Switzerland

Location

Related Publications (1)

• Niemeyer P, Hanus M, Belickas J, Laszlo T, Gudas R, Fiodorovas M, Cebatorius A, Pastucha M, Hoza P, Magos K, Izadpanah K, Pasa L, Vasarhelyi G, Sisak K, Mohyla M, Farkas C, Kessler O, Kybal S, Spiro R, Kohler A, Kirner A, Trattnig S, Gaissmaier C. Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial. Cartilage. 2022 Jan-Mar;13(1):19476035221085146. doi: 10.1177/19476035221085146.

  PMID: 35354310 DERIVED

Study Officials

• Philipp Niemeyer, MD

  Orthopaedic Surgery Munich

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Prospective, Multicenter, Single-arm Phase III

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: October 24, 2017
• Study Start: October 10, 2017
• Primary Completion: February 22, 2021
• Study Completion: February 22, 2024
• Last Updated: August 14, 2024

Record last verified: 2024-08

Locations

CH (2); LI (3); CZ (6); DE (3); HU (6)