Efficacy and Safety Study of co.Don Chondrosphere to Treat Cartilage Defects

NCT01222559 | Completed Phase 3 DMC

• 2 other identifiers: cod16HS132009-016466-82
• Study Type: interventional
• Target: 102
• Locations: 2 countries
• Sites: 12

Brief Summary

This is a prospective, phase III, multicenter, open label, randomised clinical trial of co.don chondrosphere®, a three-dimensional autologous chondrocyte transplantation product (ACT3D-CS)compared to the procedure of microfracture (MF)in the treatment of cartilage defects of knee joints. After screening visit patients were booked for arthroscopy and at that time they were randomised to either ACT3D-CS with co.don chondrosphere® (Group A) or to MF(Group B), a marrow-stimulating method based on the penetration of the subchondral bone plate at the bottom of the cartilage defect. At the time of arthroscopy Patients of group B had their procedure of MF (treatment surgery) and patients of group A had their cells harvested from healthy cartilage. The cells are cultivated for 8-10 weeks in vitro to develope 3-dimensional spheroids , that are transplanted in an open knee procedure (treatment surgery)into the defect. Patients subsequently followed the same rehabilitation program and had post-surgery visits. After the 12-month-visit a interim analyses will be performed and the 24-month-visit is defined as final assessment. Then patients have follow-up assessments up to 60 months post-treatment-surgery.

Conditions

Articular Cartilage Lesion of the Femoral Condyle

Keywords

Cartilage defects; Knee joint; Femoral Condyle

Outcome Measures

Primary Outcomes (1)

• Change of overall KOOS

  Change of overall KOOS (Knee Injury and Osteoarthritis Outcome Score)from baseline (Day 0)to final assessment compared between ACT3D-CS (co.don chondrosphere) and MF (microfracture)

  24 months after the end of the respective treatment

Secondary Outcomes (10)

• Change of overall KOOS

  12, 36, 48, 60 months after the end of the respective treatment

• Change of the 5 subscores of the KOOS

  12, 24, 36, 48, 60 months after the end of the respective treatment

• MOCART (MRI Score)

  12, 24, 36, 48 and 60 months after transplantation or microfracture

• Arthroscopy and biopsy

  24 months

• ICRS Visual Histological Assessment Score

  24 months after respective treatment

Study Arms (2)

co.don chondrosphere®

EXPERIMENTAL

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose depends on the size of the defect, recommended dose is 10-70 spheroids/cm2 defect.

Drug: co.don chondrosphere®

Micofracture

ACTIVE COMPARATOR

A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue.

Drug: co.don chondrosphere®; Procedure: Microfracture

Interventions

co.don chondrosphere® DRUG

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose depends on the size of the defect, recommended dose is 10-70 spheroids/cm2 defect.

Also known as: ACT3D-CS

Micofracture; co.don chondrosphere®

Microfracture PROCEDURE

A procedure in which the subchondral bone is perforated to allow a bloodcloth to form new tissue.

Also known as: Subchondral drilling

Micofracture

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female patients, age: between 18 and 50 years
• Defect: isolated ICRS grade III or IV single defect chondral lesions on femoral condyles
• Defect size: 1 to \< 4 cm2 after debridement to healthy cartilage up to 6 mm in depth.Assessment with MRI at screening and per estimation during arthroscopy prior to randomization
• Nearly intact chondral structure surrounding the defect as well as an intact corresponding joint area
• Informed consent signed and dated by patient
• Patient understands the strict rehabilitation protocol and follow-up programme and is willing to follow it
• In case of pain, patient agrees to use only paracetamol mono- (max 4 g/day) or combination preparation and oral and/or topic NSAIDs during the trial and to discontinue the use of oral and/or topic NSAIDs and/or paracetamol combination preparation 1 week before each visit whereas the use of paracetamol monopreparation (max 4 g/day) is allowed. However, in the morning of the visit day, no pain medication is allowed. Other pain medications are allowed during surgical procedure and may be taken for a period not exceeding 4 weeks after surgery.

You may not qualify if:

• Defects on both knees at the same time
• Radiological signs of osteoarthritis
• Osteochondritis dissecans (OCD)
• Any signs of knee instability
• Valgus or varus malalignment (more than 5° over the mechanical axis)
• Clinically relevant second cartilage lesion on the same knee
• More than 50 % resection of a meniscus in the affected knee or incomplete meniscal rim
• Rheumatoid arthritis, parainfectious or infectious arthritis, and condition after these diseases
• Pregnancy and planned pregnancy (no MRI possible)
• Obesity (Body Mass Index \>30)
• Uncontrolled diabetes mellitus
• Serious illness
• Poor general health as judged by physician
• Participation in concurrent clinical trials or previous trials within 3 months of screening
• Previous treatment with ACT in the affected knee

Sponsors & Collaborators

• co.don AG: lead

Study Sites (12)

Universitätsklinikum der Albert-Ludwig-Universität Freiburg, Department Othopädie und Traumatologie

Freiburg im Breisgau, Baden-Würrtemberg, 79106, Germany

Location

Waldkrankenhaus "Rudolf Elle" GmbH Klinik für Orthopädie und Unfallchirurgie

Eisenberg, Tühringen, 07607, Germany

Location

Gelenk-und Wirbelsäulenzentrum Steglitz

Berlin, 12163, Germany

Location

DRK-Kliniken Westend

Berlin, 14050, Germany

Location

St. Vinzenz-Hospital

Dinslaken, 46535, Germany

Location

Orthopädische Klinik der Medizinischen Hochschule Hannover

Hanover, 30625, Germany

Location

Lubinus Clinicum Kiel

Kiel, 24106, Germany

Location

DRK Krankenhaus Luckenwalde

Luckenwalde, 14943, Germany

Location

Orthopädisch-Unfallchirurgisches Zentrum

Mannheim, 68167, Germany

Location

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, 15-276, Poland

Location

Wojewódzki Szpital Chirurgii Urazowej

Piekary Śląskie, 62, Poland

Location

Centrum Medycyny Sportowej

Warsaw, Poland

Location

Related Publications (2)

• Hoburg A, Niemeyer P, Laute V, Zinser W, Becher C, Kolombe T, Fay J, Pietsch S, Kuzma T, Widuchowski W, Fickert S. Matrix-Associated Autologous Chondrocyte Implantation with Spheroid Technology Is Superior to Arthroscopic Microfracture at 36 Months Regarding Activities of Daily Living and Sporting Activities after Treatment. Cartilage. 2021 Dec;13(1_suppl):437S-448S. doi: 10.1177/1947603519897290. Epub 2020 Jan 1.

  PMID: 31893951 DERIVED

• Niemeyer P, Laute V, Zinser W, Becher C, Kolombe T, Fay J, Pietsch S, Kuzma T, Widuchowski W, Fickert S. A Prospective, Randomized, Open-Label, Multicenter, Phase III Noninferiority Trial to Compare the Clinical Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroid Technology Versus Arthroscopic Microfracture for Cartilage Defects of the Knee. Orthop J Sports Med. 2019 Jul 10;7(7):2325967119854442. doi: 10.1177/2325967119854442. eCollection 2019 Jul.

  PMID: 31317047 DERIVED

MeSH Terms

Interventions

Arthroplasty, Subchondral

Intervention Hierarchy (Ancestors)

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

Study Officials

• Stefan Fickert, Ph.D.

  Universitätsmedizin Mannheim

  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: October 15, 2010
• First Posted: October 18, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2017
• Study Completion: February 1, 2020
• Last Updated: January 27, 2021

Record last verified: 2021-01

Locations

DE (9); PL (3)