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

Articular Cartilage Lesion of the Femoral Condyle Clinical Trial

Official title:

Prospective, Randomised, Open Label, Multicentre Phase-III Clinical Trial to Compare the Efficacy and Safety of the Treatment With the Autologous Chondrocyte Transplantation Product co.Don Chondrosphere (ACT3D-CS) With Microfracture in Subjects With Cartilage Defects of the Knee With a Defect Size Between 1 an 4 cm2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01222559
• Other study ID #: cod16HS13
• Secondary ID: 2009-016466-82
• Status: Completed
• Phase: Phase 3
• Start date: October 2010
• Est. completion date: February 2020

Study information

• Verified date: January 2021
• Source: co.don AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

see above

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: February 2020
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Articular Cartilage Lesion of the Femoral Condyle

Intervention

Drug:
• 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.

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

Locations

Country	Name	City	State
Germany	DRK-Kliniken Westend	Berlin
Germany	Gelenk-und Wirbelsäulenzentrum Steglitz	Berlin
Germany	St. Vinzenz-Hospital	Dinslaken
Germany	Waldkrankenhaus "Rudolf Elle" GmbH Klinik für Orthopädie und Unfallchirurgie	Eisenberg	Tühringen
Germany	Universitätsklinikum der Albert-Ludwig-Universität Freiburg, Department Othopädie und Traumatologie	Freiburg	Baden-Würrtemberg
Germany	Orthopädische Klinik der Medizinischen Hochschule Hannover	Hannover
Germany	Lubinus Clinicum Kiel	Kiel
Germany	DRK Krankenhaus Luckenwalde	Luckenwalde
Germany	Orthopädisch-Unfallchirurgisches Zentrum	Mannheim
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok
Poland	Wojewódzki Szpital Chirurgii Urazowej	Piekary Slaskie
Poland	Centrum Medycyny Sportowej	Warszawa

Sponsors (1)

Lead Sponsor	Collaborator
co.don AG

Countries where clinical trial is conducted

Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change of overall KOOS	Change of overall KOOS(Knee Injury and Osteoarthritis Outcome Score) from baseline (Day 0) to 12 months, 36, 48, 60 months after the end of the respective treatment,compared between ACT3D-CS and MF	12, 36, 48, 60 months after the end of the respective treatment
Secondary	Change of the 5 subscores of the KOOS	Change of the 5 subscores of the KOOS (Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec), knee related Quality of life (QoL)) for both treatment groups compared between ACT3D-CS and MF	12, 24, 36, 48, 60 months after the end of the respective treatment
Secondary	MOCART (MRI Score)	MOCART (MRI Score) 12, 24, 36, 48 and 60 months after transplantation or microfracture compared between ACT3D-CS and MF	12, 24, 36, 48 and 60 months after transplantation or microfracture
Secondary	Arthroscopy and biopsy	Arthroscopy and biopsy at 24 months after transplantation/ microfracture, assessment of cartilage repair after ACT3D and microfracture to be compared between ACT3D-CS and MF	24 months
Secondary	ICRS Visual Histological Assessment Score	ICRS Visual Histological Assessment Score at final assessment (24 months) compared between ACT3D-CS and MF	24 months after respective treatment
Secondary	Bern Score and additional histological assessment scores	Bern Score and additional histological assessment scores at final assessment (24 months) compared between ACT3D-CS and MF	24 months after the respective treatment
Secondary	Change of ICRS/IKDC	Change of ICRS/IKDC from baseline (Day 0) to 12, 24, 36, 48 and 60 months after the end of the respective treatment, compared between ACT3D-CS and MF	12, 24, 36, 48 and 60 months after the end of the respective treatment
Secondary	Change of modified Lysholm Score	Change of modified Lysholm Score from baseline (Day 0) to 12, 24, 36, 48 and 60 months after the end of the respective treatment compared between ACT3D-CS and MF	12, 24, 36, 48 and 60 months after the end of the respective treatment
Secondary	Days of absence from work (employment) and/or days of inability to follow usual activities	Days of absence from work (employment) and/or days of inability to follow usual activities during the last year or since the last visit, respectively, and time point when patient was back to work and/or to follow usual activities	annual
Secondary	Safety Parameters	Frequence and type of adverse Events Vital signs Physical examination Concomitant pain medication Laboratory parameters	3,12,24 months after respective treatment