Assessment of Efficacy and Safety of 3 Different Doses of co.Don Chondrosphere to Treat Large Cartilage Defects

NCT ID: NCT01225575

Last Updated: 2018-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2018-03-31

Brief Summary

This is a prospective, randomised, open label, multicentre Phase II clinical trial to investigate the efficacy and safety of the treatment of large defects with 3 different doses of the autologous chondrocyte transplantation product co.don chondrosphere® (ACT3D-CS) in subjects with cartilage defects of the knee.

After screening visit patients were booked for arthroscopy and had their cells harvesting from healthy cartilage. After the arthroscopy the patients were randomised in one of the three dose-groups. 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 of all dose groups subsequently followed the same rehabilitation program and had post-surgery visits. The 12-month-visit is defined as final assessment. Then patients have follow-up assessments up to 60 months.

Detailed Description

see above

Conditions

Large Articular Cartilage Lesions of the Femoral; Condyle, Trochlea, Tibia or Retropatellar

Study Design

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

Study Groups

co.don chondrosphere®, 3-7 spheroids/cm2

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes.

The dose in group A is 3-7 spheroids/cm2 defect

Group Type: ACTIVE_COMPARATOR

co.don chondrosphere®

Intervention Type: DRUG

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes.

The dose in group A is 3-7 spheroids/cm2 defect, in group B 10-30 spheroids/cm2 defect and in group C 40-70 spheroids/cm2 defect

co.don chondrosphere®,10-30spheroids/cm2

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes.

The dose in group B is 10-30 spheroids/cm2 defect

Group Type: ACTIVE_COMPARATOR

co.don chondrosphere®

Intervention Type: DRUG

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes.

The dose in group A is 3-7 spheroids/cm2 defect, in group B 10-30 spheroids/cm2 defect and in group C 40-70 spheroids/cm2 defect

co.don chondrosphere®,40-70spheroids/cm2

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes.

The dose in group C is 40-70 Spheroids/cm2 defect

Group Type: ACTIVE_COMPARATOR

co.don chondrosphere®

Intervention Type: DRUG

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes.

The dose in group A is 3-7 spheroids/cm2 defect, in group B 10-30 spheroids/cm2 defect and in group C 40-70 spheroids/cm2 defect

Interventions

co.don chondrosphere®

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes.

The dose in group A is 3-7 spheroids/cm2 defect, in group B 10-30 spheroids/cm2 defect and in group C 40-70 spheroids/cm2 defect

Intervention Type: DRUG

Other Intervention Names

ACT3D-CS

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 on medial or lateral femoral condyle, trochlea, tibia and retropatellar defects, also OCD (in case of OCD: Bone grafting up to the level of the original bone lamella must be performed if bone loss exceeds 3 mm in depth)

3. Defect size: ≥ 4 to 10 cm2 after debridement to healthy cartilage; chondral lesions, including osteochondritis dissecans on femoral condyle, trochlea, tibia,retropatellar defects up to 6 mm in depth. Assessment with MRI at Screening and per estimation during arthroscopy prior to randomization

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

5. Informed consent signed by patient

6. Patient understands 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 mono-preparation (max 4 g/day) is allowed. However, in the morning of the visit day, no pain medication is allowed. However, in the morning of the visit day, no pain medication is allowed. Other pain medications are allowed during surgical operation 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. Any signs of knee instability

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

5. Clinically relevant second cartilage lesion on the same knee

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

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

8. Pregnancy and planned pregnancy (no MRI possible)

9. Obesity (Body Mass Index >30)

10. Uncontrolled diabetes mellitus

11. Serious illness

12. Poor general health as judged by physician

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

14. Previous treatment with ACT in the affected knee

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

16. Alcohol or drug (medication) abuse

17. Meniscal transplant in the affected knee

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

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

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

21. Taking specific osteoarthritis drugs such as chondroitin sulfate, diacerein, n-glucosamine, piascledine, capsaicin within 2 weeks of baseline

22. Corticosteroid treatment by systemic or intra-articular route within the last month of baseline or intramuscular or oral corticosteroids within the last 2 weeks of baseline

23. Chronic use of anticoagulants

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

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

26. 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

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

ATOS Klinikum Heidelberg, Zentrum für Knie- und Fußchirurgie

Heidelberg, Baden-Würrtemberg, 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

Orthopädiezentrum München Ost

München, , Germany

Countries

Germany

References

Hoburg A, Niemeyer P, Laute V, Zinser W, John T, Becher C, Izadpanah K, Diehl P, Kolombe T, Fay J, Siebold R, Fickert S. Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial. Orthop J Sports Med. 2022 Jan 18;10(1):23259671211053380. doi: 10.1177/23259671211053380. eCollection 2022 Jan.

Reference Type: DERIVED

PMID: 35071653 (View on PubMed)

Becher C, Laute V, Fickert S, Zinser W, Niemeyer P, John T, Diehl P, Kolombe T, Siebold R, Fay J. Safety of three different product doses in autologous chondrocyte implantation: results of a prospective, randomised, controlled trial. J Orthop Surg Res. 2017 May 12;12(1):71. doi: 10.1186/s13018-017-0570-7.

Reference Type: DERIVED

PMID: 28499391 (View on PubMed)

Niemeyer P, Laute V, John T, Becher C, Diehl P, Kolombe T, Fay J, Siebold R, Niks M, Fickert S, Zinser W. The Effect of Cell Dose on the Early Magnetic Resonance Morphological Outcomes of Autologous Cell Implantation for Articular Cartilage Defects in the Knee: A Randomized Clinical Trial. Am J Sports Med. 2016 Aug;44(8):2005-14. doi: 10.1177/0363546516646092. Epub 2016 May 20.

Reference Type: DERIVED

PMID: 27206690 (View on PubMed)

Other Identifiers

2009-016816-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

cod 16HS14

Identifier Type: -

Identifier Source: org_study_id