Articular Cartilage Lesion of the Femoral CondylePhase 3NCT01222559
Efficacy and Safety Study of co.Don Chondrosphere to Treat Cartilage Defects
A Phase 3 study testing co.don chondrosphere® and Microfracture in people with Articular Cartilage Lesion of the Femoral Condyle, run by co.don AG at 12 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Articular Cartilage Lesion of the Femoral Condyle
- What is being tested?
- co.don chondrosphere® and Microfracture
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 12 sitesin 2 countries
- Study dates
- Oct 2010to Feb 2020
- Phase
- Phase 3
- 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 chondral lesions on femoral condyles
- 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
- Nearly intact chondral structure surrounding the defect as well as an intact corresponding joint area
- Informed consent signed and dated by patient
- Patient understands the 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 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.
Who cannot join
- Defects on both knees at the same time
- Radiological signs of osteoarthritis
- Osteochondritis dissecans (OCD)
- 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
Show all 28Show fewer
- 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
- 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 before baseline
- Taking specific osteoarthritis drugs such as chondroïtin sulfate, diacerein, nglucosamine,piascledine, capsaicin within 2 weeks before baseline
- 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
- 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 virus (HCV) infection
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Germany9 sites
Gelenk-und Wirbelsäulenzentrum Steglitz
Berlin, 12163
DRK-Kliniken Westend
Berlin, 14050
St. Vinzenz-Hospital
Dinslaken, 46535
Waldkrankenhaus "Rudolf Elle" GmbH Klinik für Orthopädie und Unfallchirurgie
Eisenberg, Tühringen, 07607
Universitätsklinikum der Albert-Ludwig-Universität Freiburg, Department Othopädie und Traumatologie
Freiburg im Breisgau, Baden-Würrtemberg, 79106
Orthopädische Klinik der Medizinischen Hochschule Hannover
Hanover, 30625
Lubinus Clinicum Kiel
Kiel, 24106
DRK Krankenhaus Luckenwalde
Luckenwalde, 14943
Orthopädisch-Unfallchirurgisches Zentrum
Mannheim, 68167
Poland3 sites
Uniwersytecki Szpital Kliniczny w Białymstoku
Bialystok, 15-276
Wojewódzki Szpital Chirurgii Urazowej
Piekary Śląskie, 62
Centrum Medycyny Sportowej
Warsaw
About this study
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
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.
Read the detailed description
see above
- Being tested
- co.don chondrosphere®, Microfracture
- Keywords
- Cartilage defects, Knee joint, Femoral Condyle
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 depends on the size of the defect, recommended dose is 10-70 spheroids/cm2 defect.
MicrofractureProcedure or surgery
Also called Subchondral drilling
A procedure in which the subchondral bone is perforated to allow a bloodcloth to form new tissue.
| Study group | Role | What they receive |
|---|---|---|
| co.don chondrosphere® | Experimental | 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. Receives: Drug: co.don chondrosphere® |
| Micofracture | Active comparator | A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue. Receives: Drug: co.don chondrosphere®; Procedure: Microfracture |
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 compared between ACT3D-CS (co.don chondrosphere) and MF (microfracture)
Measured: 24 months after the end of the respective treatment
Secondary outcomes (10)
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
Measured: 12, 36, 48, 60 months after the end of the respective treatment
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
Measured: 12, 24, 36, 48, 60 months after the end of the respective treatment
MOCART (MRI Score)
MOCART (MRI Score) 12, 24, 36, 48 and 60 months after transplantation or microfracture compared between ACT3D-CS and MF
Measured: 12, 24, 36, 48 and 60 months after transplantation or microfracture
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
Measured: 24 months
ICRS Visual Histological Assessment Score
ICRS Visual Histological Assessment Score at final assessment (24 months) compared between ACT3D-CS and MF
Measured: 24 months after respective treatment
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
Measured: 24 months after the respective treatment
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
Measured: 12, 24, 36, 48 and 60 months after the end of the respective treatment
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
Measured: 12, 24, 36, 48 and 60 months after the end of the respective treatment
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
Safety Parameters
Frequence and type of adverse Events Vital signs Physical examination Concomitant pain medication Laboratory parameters
Measured: 3,12,24 months after respective treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionSep 2017
- Study completionFeb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Articular Cartilage Lesion of the Femoral CondyleStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 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
- NCT01222559
- Sponsor's protocol ID
- cod16HS13
- Other IDs
- 2009-016466-82, 2009
- Status last verified
- Jan 2021
- First submitted
- 15 Oct 2010
- Last updated
- 27 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31893951Niemeyer 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.
PubMed 31317047
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01222559
- Acronym / sponsor ID
- cod16HS13
- Keywords
- Cartilage defects, Knee joint, Femoral Condyle
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- co.don AGIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- Sep 2017 (actual)
- Study completion
- Feb 2020 (actual)
- First posted
- 18 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, 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| co.don chondrosphere® | Experimental | 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. |
| Micofracture | Active comparator | Drug: co.don chondrosphere®, Procedure: MicrofractureA procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue. |
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 chondral lesions on femoral condyles
- 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
- Nearly intact chondral structure surrounding the defect as well as an intact corresponding joint area
- Informed consent signed and dated by patient
Key exclusion criteria (28 listed)
- Defects on both knees at the same time
- Radiological signs of osteoarthritis
- Osteochondritis dissecans (OCD)
- Any signs of knee instability
- Valgus or varus malalignment (more than 5° over the mechanical axis)
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 depends on the size of the defect, recommended dose is 10-70 spheroids/cm2 defect. | Drug | Micofracture, co.don chondrosphere® |
| MicrofractureAlso: Subchondral drillingA procedure in which the subchondral bone is perforated to allow a bloodcloth to form new tissue. | Procedure or surgery | Micofracture |
Primary outcome
Change of overall KOOS
Time frame: 24 months after the end of the respective treatment
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)
10 secondary outcomes
Change of overall KOOS
Time frame: 12, 36, 48, 60 months after the end of the respective treatment
Change of the 5 subscores of the KOOS
Time frame: 12, 24, 36, 48, 60 months after the end of the respective treatment
MOCART (MRI Score)
Time frame: 12, 24, 36, 48 and 60 months after transplantation or microfracture
Arthroscopy and biopsy
Time frame: 24 months
ICRS Visual Histological Assessment Score
Time frame: 24 months after respective treatment
Bern Score and additional histological assessment scores
Time frame: 24 months after the respective treatment
Change of ICRS/IKDC
Time frame: 12, 24, 36, 48 and 60 months after the end of the respective treatment
Change of modified Lysholm Score
Time frame: 12, 24, 36, 48 and 60 months after the end of the respective treatment
Days of absence from work (employment) and/or days of inability to follow usual activities
Time frame: annual
Safety Parameters
Time frame: 3,12,24 months after respective treatment
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 27 Jan 2021.
- Derived from this study: PubMed 31893951Hoburg 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.
- Derived from this study: PubMed 31317047Niemeyer 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.
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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
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing co.don chondrosphere® and Microfracture in people with Articular Cartilage Lesion of the Femoral Condyle, run by co.don AG at 12 sites in 2 countries.
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 28 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 27 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany, Poland. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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: 24 months after the end of the respective treatment). 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 NCT01222559, which also lists 2 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 27 Jan 2021.