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

NCT ID: NCT01222559

Last Updated: 2021-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2020-02-29

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.

Detailed Description

see above

Conditions

Articular Cartilage Lesion of the Femoral Condyle

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

co.don chondrosphere®

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.

Group Type: EXPERIMENTAL

co.don chondrosphere®

Intervention Type: 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.

Micofracture

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

Group Type: ACTIVE_COMPARATOR

co.don chondrosphere®

Intervention Type: 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.

Microfracture

Intervention Type: PROCEDURE

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

Interventions

co.don chondrosphere®

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.

Intervention Type: DRUG

Microfracture

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

Intervention Type: PROCEDURE

Other Intervention Names

ACT3D-CS; Subchondral drilling

Eligibility Criteria

Inclusion Criteria

1. Male or female patients, age: between 18 and 50 years

2. Defect: isolated ICRS grade III or IV single defect chondral lesions on femoral condyles

3. 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

4. Nearly intact chondral structure surrounding the defect as well as an intact corresponding joint area

5. Informed consent signed and dated by patient

6. Patient understands the strict rehabilitation protocol and follow-up programme and is willing to follow it

7. 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.

Exclusion Criteria

1. Defects on both knees at the same time

2. Radiological signs of osteoarthritis

3. Osteochondritis dissecans (OCD)

4. Any signs of knee instability

5. Valgus or varus malalignment (more than 5° over the mechanical axis)

6. Clinically relevant second cartilage lesion on the same knee

7. More than 50 % resection of a meniscus in the affected knee or incomplete meniscal rim

8. Rheumatoid arthritis, parainfectious or infectious arthritis, and condition after these diseases

9. Pregnancy and planned pregnancy (no MRI possible)

10. Obesity (Body Mass Index >30)

11. Uncontrolled diabetes mellitus

12. Serious illness

13. Poor general health as judged by physician

14. Participation in concurrent clinical trials or previous trials within 3 months of screening

15. Previous treatment with ACT in the affected knee

16. Microfracture performed less than 1 year before screening in the affected knee

17. Alcohol or drug (medication) abuse

18. Meniscal transplant in the affected knee

19. Meniscal suture (in the affected knee) three months prior to baseline

20. Mosaicplasty (Osteoarticular Transplant System, OATS) in the affected knee

21. Having received hyaluronic acid intra-articular injections in the affected knee within the last 3 months before baseline

22. Taking specific osteoarthritis drugs such as chondroïtin sulfate, diacerein, nglucosamine,piascledine, capsaicin within 2 weeks before baseline

23. Corticosteroid treatment by systemic or intraarticular route within the last month of baseline or intramuscular or oral corticosteroïds within the last 2 weeks before baseline

24. Chronic use of anticoagulants

25. Any concomitant painful or disabling disease of the spine, hips or lower limbs that would interfere with evaluation of the afflicted knee

26. Any clinically significant or symptomatic vascular or neurological disorder of the lower extremities

27. Any evidence of the following diseases in the affected knee: septic arthritis, inflammatory joint disease, recurrent episodes of pseudogout, Paget's disease of bone, ochronosis, acromegaly, haemochromatosis, Wilson's disease, primary osteochondromatosis, heritable disorders, collagen gene mutation

28. Current diagnosis of osteomyelitis, human immunodeficiency virus (HIV-1,-2) and/or hepatitis C virus (HCV) infection

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

co.don AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefan Fickert, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Universitätsmedizin Mannheim

Locations

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

Freiburg im Breisgau, Baden-Würrtemberg, Germany

Waldkrankenhaus "Rudolf Elle" GmbH Klinik für Orthopädie und Unfallchirurgie

Eisenberg, Tühringen, Germany

Gelenk-und Wirbelsäulenzentrum Steglitz

Berlin, , Germany

DRK-Kliniken Westend

Berlin, , Germany

St. Vinzenz-Hospital

Dinslaken, , Germany

Orthopädische Klinik der Medizinischen Hochschule Hannover

Hanover, , Germany

Lubinus Clinicum Kiel

Kiel, , Germany

DRK Krankenhaus Luckenwalde

Luckenwalde, , Germany

Orthopädisch-Unfallchirurgisches Zentrum

Mannheim, , Germany

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, , Poland

Wojewódzki Szpital Chirurgii Urazowej

Piekary Śląskie, , Poland

Centrum Medycyny Sportowej

Warsaw, , Poland

Countries

Germany; Poland

References

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.

Reference Type: DERIVED

PMID: 31893951 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31317047 (View on PubMed)

Other Identifiers

2009-016466-82

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

cod16HS13

Identifier Type: -

Identifier Source: org_study_id