Large Articular Cartilage Lesions of the FemoralPhase 2NCT01225575
Assessment of Efficacy and Safety of 3 Different Doses of co.Don Chondrosphere to Treat Large Cartilage Defects
A Phase 2 study testing co.don chondrosphere® in people with Large Articular Cartilage Lesions of the Femoral and Condyle, Trochlea, Tibia or Retropatellar, run by co.don AG at 10 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Large Articular Cartilage Lesions of the Femoral, Condyle, Trochlea, Tibia or Retropatellar
- What is being tested?
- co.don chondrosphere®
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 10 sitesGermany
- Study dates
- Oct 2010to Mar 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 27Show fewer
- 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
- Alcohol or drug (medication) abuse
- Meniscal transplant in the affected knee
- Meniscal suture (in the affected knee) three months prior to baseline
- Mosaicplasty (Osteoarticular Transplant System, OATS) in the affected knee
- Having received hyaluronic acid intra-articular injections in the affected knee within the last 3 months of baseline
- Taking specific osteoarthritis drugs such as chondroitin sulfate, diacerein, n-glucosamine, piascledine, capsaicin within 2 weeks of baseline
- 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
- Chronic use of anticoagulants
- Any concomitant painful or disabling disease of the spine, hips or lower limbs that would interfere with evaluation of the afflicted knee
- Any clinically significant or symptomatic vascular or neurological disorder of the lower extremities
- 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
- Current diagnosis of osteomyelitis, human immunodeficiency virus (HIV-1, 2) and/or hepatitis C (HCV) infection
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Germany10 sites
Gelenk-und Wirbelsäulenzentrum Steglitz
Berlin, 12163
DRK-Kliniken Westend
Berlin, 14050
St. Vinzenz-Hospital
Dinslaken, 46535
Universitätsklinikum der Albert-Ludwig-Universität Freiburg, Department Othopädie und Traumatologie
Freiburg im Breisgau, Baden-Würrtemberg, 79106
Orthopädische Klinik der Medizinischen Hochschule Hannover
Hanover, 30625
ATOS Klinikum Heidelberg, Zentrum für Knie- und Fußchirurgie
Heidelberg, Baden-Würrtemberg, 69115
Lubinus Clinicum Kiel
Kiel, 24106
DRK Krankenhaus Luckenwalde
Luckenwalde, 14943
Orthopädisch-Unfallchirurgisches Zentrum
Mannheim, 68167
Orthopädiezentrum München Ost
München, 85567
About this study
Official title: Prospective, Randomised, Open Label, Multicentre Phase II Clinical Trial to Investigate the Efficacy and Safety of the Treatment of Large Cartilage Knee Defects(4-10 cm²) With 3 Diff. Doses of the ACT Product co.Don Chondrosphere®
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.
Read the detailed description
see above
- Conditions
- Large Articular Cartilage Lesions of the Femoral, Condyle, Trochlea, Tibia or Retropatellar
- Being tested
- co.don chondrosphere®
- Keywords
- large cartilage defects, knee joint, femoral condyle, tibia, trochlear, retropatellar
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
co.don chondrosphere®Drug
Also called ACT3D-CS
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: co.don chondrosphere® |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months after transplantation
Secondary outcomes (11)
Change of overall KOOS
Change of overall KOOS from baseline (Day 0) to 24,36, 48 and 60 months follow-up, FU) after transplantation determined for each dosage group and compared between the dosage groups
Measured: 24, 36, 48, 60 months after transplantation
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)) determined for each dosage group and between the dosage groups
Measured: 12, 24, 36 ,48, 60 months after transplantation
Assessment of MRIs by the MOCART-Score (MRI Score)
Assessment of MRIs by the MOCART-Score (MRI Score) at 12, 24, 36, 48 and 60 months after transplantation compared between the dosage groups
Measured: 12, 24, 36, 48 and 60 months after transplantation
Assessment of cartilage repair using an Arthroscopy and take a biopsy
Arthroscopy and biopsy at 12 months after transplantation, assessment of cartilage repair after ACT3D to be compared for each dosage group and between the dosage groups
Measured: 12 months after transplantation
Assessment of the histology from the biopsy by ICRS Visual Histological Assessment Score
Assessment of the ICRS Visual Histological Assessment Score at final assessment (FA, 12 months) determined for each dosage group and compared between the dosage groups
Measured: 12 months after transplantation
Assessment of the histology from the biopsy by the Bern Score and additional histological scores
Assessment of the histology from the biopsy by the Bern Score and additional histological assessment scores at final assessment (12 months) determined for each dosage group and compared between the dosage groups
Measured: 12 months after transplantation
Change of ICRS/IKDC
Change of ICRS/IKDC from baseline (Day 0) to 12, 24, 36, 48 and 60 months after transplantation determined for each dosage group and compared between the dosage groups
Measured: 12, 24, 36, 48 and 60 months after transplantation
Assessment of change of modified Lysholm Score
Change of modified Lysholm Score from baseline (Day 0) to 12, 24, 36, 48 and 60 months after transplantation determined for each dosage group and compared between the dosage the groups
Measured: 12, 24, 36, 48 and 60 months after transplantation
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
Measured: annual
Frequency and type of adverse events
Frequency and type of adverse events
Measured: 3,12, 24, 36, 48, 60 months after transplantation
Measurement of blood pressure, pulse and laboratory parameters
Measurement of the vital signs and physical examination, laboratory parameters at 3 and 12 months after transplantation.
Measured: 3, 6, 12, 24, 36, 48, 60 months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionSep 2013
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Large Articular Cartilage Lesions of the FemoralStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- co.don AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stefan Fickert, Ph.D., Principal investigator, Universitätsmedizin Mannheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01225575
- Sponsor's protocol ID
- cod 16HS14
- Other IDs
- 2009-016816-20, 2009
- Status last verified
- Mar 2018
- First submitted
- 18 Oct 2010
- Last updated
- 19 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 35071653Becher 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.
PubMed 28499391Niemeyer 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.
PubMed 27206690
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomised, Open Label, Multicentre Phase II Clinical Trial to Investigate the Efficacy and Safety of the Treatment of Large Cartilage Knee Defects(4-10 cm²) With 3 Diff. Doses of the ACT Product co.Don Chondrosphere®
- ClinicalTrials.gov ID
- NCT01225575
- Acronym / sponsor ID
- cod 16HS14
- Conditions
- Large Articular Cartilage Lesions of the Femoral, Condyle, Trochlea, Tibia or Retropatellar
- Keywords
- large cartilage defects, knee joint, femoral condyle, tibia, trochlear, retropatellar
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- co.don AGIndustry (pharma, biotech, devices)
- Study start
- Oct 2010 (actual)
- Primary completion
- Sep 2013 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 21 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| co.don chondrosphere®, 3-7 spheroids/cm2 | Active comparator | Drug: 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 |
| co.don chondrosphere®,10-30spheroids/cm2 | Active comparator | Drug: co.don chondrosphere®co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group B is 10-30 spheroids/cm2 defect |
| co.don chondrosphere®,40-70spheroids/cm2 | Active comparator | Drug: co.don chondrosphere®co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group C is 40-70 Spheroids/cm2 defect |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| co.don chondrosphere®Also: ACT3D-CSco.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 | Drug | co.don chondrosphere®, 3-7 spheroids/cm2, co.don chondrosphere®,10-30spheroids/cm2, co.don chondrosphere®,40-70spheroids/cm2 |
Primary outcome
Change of overall KOOS
Time frame: 12 months after transplantation
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.
11 secondary outcomes
Change of overall KOOS
Time frame: 24, 36, 48, 60 months after transplantation
Change of the 5 subscores of the KOOS
Time frame: 12, 24, 36 ,48, 60 months after transplantation
Assessment of MRIs by the MOCART-Score (MRI Score)
Time frame: 12, 24, 36, 48 and 60 months after transplantation
Assessment of cartilage repair using an Arthroscopy and take a biopsy
Time frame: 12 months after transplantation
Assessment of the histology from the biopsy by ICRS Visual Histological Assessment Score
Time frame: 12 months after transplantation
Assessment of the histology from the biopsy by the Bern Score and additional histological scores
Time frame: 12 months after transplantation
Change of ICRS/IKDC
Time frame: 12, 24, 36, 48 and 60 months after transplantation
Assessment of change of modified Lysholm Score
Time frame: 12, 24, 36, 48 and 60 months after transplantation
Days of absence from work (employment) and/or days of inability to follow usual activities
Time frame: annual
Frequency and type of adverse events
Time frame: 3,12, 24, 36, 48, 60 months after transplantation
Measurement of blood pressure, pulse and laboratory parameters
Time frame: 3, 6, 12, 24, 36, 48, 60 months after transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2018.
- Derived from this study: PubMed 35071653Hoburg 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.
- Derived from this study: PubMed 28499391Becher 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.
- Derived from this study: PubMed 27206690Niemeyer 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Fickert, Ph.D. principal investigator
Universitätsmedizin Mannheim
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing co.don chondrosphere® in people with Large Articular Cartilage Lesions of the Femoral and Condyle, Trochlea, Tibia or Retropatellar, run by co.don AG at 10 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of overall KOOS (time frame: 12 months after transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01225575, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2018.