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

NCT01225575 | Completed Phase 2 DMC

• 2 other identifiers: cod 16HS142009-016816-20
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 10

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.

Conditions

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

Keywords

large cartilage defects; knee joint; femoral condyle, tibia, trochlear, retropatellar

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 (FA)determined for each dosage group and between the dosage groups.

  12 months after transplantation

Secondary Outcomes (11)

• Change of overall KOOS

  24, 36, 48, 60 months after transplantation

• Change of the 5 subscores of the KOOS

  12, 24, 36 ,48, 60 months after transplantation

• Assessment of MRIs by the MOCART-Score (MRI Score)

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

• Assessment of cartilage repair using an Arthroscopy and take a biopsy

  12 months after transplantation

• Assessment of the histology from the biopsy by ICRS Visual Histological Assessment Score

  12 months after transplantation

Study Arms (3)

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

ACTIVE COMPARATOR

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group A is 3-7 spheroids/cm2 defect

Drug: co.don chondrosphere®

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

ACTIVE COMPARATOR

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group B is 10-30 spheroids/cm2 defect

Drug: co.don chondrosphere®

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

ACTIVE COMPARATOR

co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group C is 40-70 Spheroids/cm2 defect

Drug: co.don chondrosphere®

Interventions

co.don chondrosphere® 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

Also known as: ACT3D-CS

co.don chondrosphere®, 3-7 spheroids/cm2; co.don chondrosphere®,10-30spheroids/cm2; co.don chondrosphere®,40-70spheroids/cm2

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 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)
• 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
• Nearly intact surrounding chondral structure around the defect as well as corresponding joint area
• Informed consent signed by patient
• Patient understands 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 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.

You may not qualify if:

• Defects on both knees at the same time
• Radiological signs of osteoarthritis
• 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
• Microfracture performed less than 1 year before screening in the affected knee

Sponsors & Collaborators

• co.don AG: lead

Study Sites (10)

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

Freiburg im Breisgau, Baden-Würrtemberg, 79106, Germany

Location

ATOS Klinikum Heidelberg, Zentrum für Knie- und Fußchirurgie

Heidelberg, Baden-Würrtemberg, 69115, 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

Orthopädiezentrum München Ost

München, 85567, Germany

Location

Related Publications (3)

• 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.

  PMID: 35071653 DERIVED

• 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.

  PMID: 28499391 DERIVED

• 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.

  PMID: 27206690 DERIVED

Study Officials

• Stefan Fickert, Ph.D.

  Universitätsmedizin Mannheim

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2010
• First Posted: October 21, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: March 1, 2018
• Last Updated: March 19, 2018

Record last verified: 2018-03

Locations

DE (10)