Osteoarthritis, KneePhase 2NCT01221441
Study of TG-C in Patients With Grade 3 Degenerative Joint Disease of the Knee
A Phase 2 study testing TissueGene-C and Normal Saline in people with Osteoarthritis, Knee, run by Kolon TissueGene, Inc. at 5 sites in United States.
Trial summary
The purpose of this study is to see if we can safely regenerate cartilage without invasive surgery using a biologic product called TissueGene-C. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- TissueGene-C and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 5 sitesUnited States
- Study dates
- May 2011to Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or Female subject
- Age 18 to 70 years
- In general good health as evidenced by physical examination, normal hematology, serum chemistry, and urinalysis screening laboratory results, and a negative history of significant organ system disorders. All laboratory values must be within 20% of normal ranges.
- Body Mass Index (BMI) should be between '18.5 - 45.5'. The applied scale is the same for both men and women.
- Blood Pressure measurements - Systolic Blood Pressure should be between 90-160mm. Hg, and Diastolic Blood Pressure between 50-90mm.Hg,
- Patients with Grade 3 chronic osteoarthritis of the knee as determined by the Radiographic Criteria of Kellgren and Lawrence.
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- Symptom of pain for more than four (4) consecutive months and intensity of ≥ 40 and ≤ 90 on the 100-mm scale.
- Patients should be cleared to use protocol specified equipment: 3T MRI.
- Patients providing written informed consent after the nature of the study is fully explained and understood by the patient.
Who cannot join
- Age 71 or older
- Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results.
- Patients taking non-steroidal anti-inflammatory medications within 14 days of baseline visit unless washed out as per section 3.6.4 above.
- Patients taking steroidal anti-inflammatory medications within 2 months of baseline visit.
- Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug test at the time of screening.
- Patients receiving injections to the treated knee within 2 months prior to study entry
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- Patients who are contraindicated for 3T MRI.
- Patients who are pregnant or currently breast-feeding children.
- Patients with systemic, rheumatic or inflammatory disease of the knee or chondrocalcinosis, hemochromatosis, inflammatory arthritis, necrosis of the femoral condyle, arthropathy of the knee associated with juxta-articular Paget's disease of the femur or tibia, ochronosis, hemophilic arthropathy, infectious arthritis, Charcot's knee joint, villonodular synovitis, synovial chondromatosis, and/or history of inflammatory arthropathy.
- Patients with ongoing infectious disease, including HIV and hepatitis B or C.
- Patients with clinically significant cardiovascular, renal, hepatic, endocrine disease, cancer, or Type I diabetes.
- Patients participating in a study of an experimental drug or medical device within 30 days of study entry.
- Patients that will be unable to comply with the requisite study follow-up and are not able to complete all of the follow-up office visits and 3T MRI exams.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Commonwealth Orthopedics
Arlington, Virginia, 22205
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Rothman Institute
Philadelphia, Pennsylvania, 19107
Advent Clinical Research
Pinellas Park, Florida, 33781
University Orthopedics
State College, Pennsylvania, 16801
About this study
Official title: A Phase II Study to Determine the Efficacy and Safety of Allogeneic Human Chondrocytes Expressing TGF-β1 (TissueGene-C) in Patients With Grade 3 Chronic Degenerative Joint Disease of the Knee
The purpose of this study is to see if we can safely regenerate cartilage without invasive surgery using a biologic product called TissueGene-C.
Read the detailed description
Protocol TGC09201 is a multi-center, double-blind, placebo-controlled, randomized study. A total of one hundred (100) adults with grade 3 chronic degenerative joint disease (DJD) of the knee joint (as determined by radiographic examination) will be enrolled into the study. TissueGene-C will be administered intra-articularly once via x-ray guidance. TissueGene-C will be administered at a dose of 3 x 10e7 cells. Patients receiving control treatment will receive a single normal saline injection.
The objectives of this study are to:
- Evaluate the efficacy of TissueGene-C with regard to knee functionality and symptoms of knee osteoarthritis including pain.
- Evaluate the safety of administration of a single intra-articular dose of TissueGene-C as evidenced by observation of the injection site for irritation or other abnormalities, the incidence and severity of adverse events, and the changes in physical examination findings and laboratory tests, including immune analyses.
- Evaluate the incidence and dose of analgesia and/or anti-inflammatory medication.
- Evaluate the regeneration of hyaline cartilage as determined by 3T magnetic resonance imaging (MRI).
- Evaluate distribution of hChonJb#7 cells out of the injection site.
- Evaluate the efficacy of TissueGene-C by evaluating the need for total knee arthroplasty after treatment
- Conditions
- Osteoarthritis, Knee
- Being tested
- TissueGene-C, Normal Saline
- Keywords
- Cartilage, Knee, Osteoarthritis
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TissueGene-CBiological
Also called TG-C
Single intraarticular injection at 3 x 10e7 cells
Normal SalineDrug
Also called 0.9% Saline
Single intraarticular injection of normal saline as a placebo control
| Study group | Role | What they receive |
|---|---|---|
| TissueGene-C | Experimental | TissueGene-C at 3 x 10e7 cells per injection (intraarticular) Receives: Biological: TissueGene-C |
| Placebo Control | Placebo comparator | Normal Saline injection Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 1 Year
Symptoms, pain and function of the knee joint determined and scored using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation (Total Score, range 0-100 with higher scores better). Linear mixed model used for analysis.
Measured: 1 Year
Change From Baseline in Visual Analog Scale (VAS) Score at 1 Year
Reduction in pain as measured by a 100 mm visual analog scale (0= no pain; 100 = extreme pain) from Baseline to 1 Year. Linear mixed model used for analysis.
Measured: 1 Year
Secondary outcomes (11)
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 Years
Symptoms, pain and functionality of the knee joint as determined by Total Score of the Knee Injury and Osteoarthritis Outcome Score (KOOS) (Range 0-100 with higher scores indicating healthier outcomes). Linear mixed model used for analysis.
Measured: 2 Years
Change From Baseline in Articular Cartilage Damage in the Knee as Determined by the Lysholm Knee Score at 2 Years
Measurement to assess outcomes of various chondral disorders of the knee determined by the Lysholm Knee Scale (Range 0-100 with higher scores better). Linear mixed model used for analysis.
Measured: 2 Years
Comparative Evaluation of Knee Magnetic Resonance Images (MRIs) From Baseline to 1 Year
Comparison of pre-procedure 3T MRI scans to those obtained at months 12 following dose administration by an independent radiographic reviewer. Evaluations will be scored using Whole Organ Magnetic Resonance imaging Score (WORMS) Cartilage Morphology Subscore (Range 0-6, with higher scores being worse)
Measured: 1 Year
Change in Pain Severity From Baseline to 2 Years as Assessed by Questionnaire
Change in pain severity (on a scale from 1 to 4) from baseline to 2 years as measured by a questionnaire (lower scores better)
Measured: 2 Years
Number of Participants With Change in Pain Severity Measured by Incidence and Dose of Analgesia
The number of participants that had a change in pain severity as measured by the incidence and dose of analgesic medications
Measured: 2 Years
Change From Baseline in Knee Function as Determined by the Lower Extremity Functional Scale at 2 Years
Assessment of knee function as determined by the Lower Extremity Functional Scale (LEFS); change from baseline to 2 years (Range 0-80 with higher scores signifying lower difficulty in performing knee functions)
Measured: 2 Years
The Incidence of Total Knee Arthroplasty
Quantification of the incidence of total knee arthroplasty of the treated knee subsequent to treatment with TissueGene-C
Measured: 2 Years
The Number of Patients Experiencing Injection Site Reactions Related to Treatment
The number of patients with observations of the administration site deemed related to treatment with either active or placebo, including arthralgia, swelling, irritation, pain, stiffness or abnormalities
Measured: 2 Years
The Incidence and Severity of Adverse Events in Treated Patients
The incidence and severity of adverse events assessed through 104 weeks (2 years) after dose administration
Measured: 2 Years
Number of Participants With Adverse Events Due to Clinically Significant Changes in Hematology and Urinalysis Tests
The number of participants with changes in clinical hematology, chemistry, and urinalysis test results through 2 years that were considered Adverse Events
Measured: 2 Years
Change in SF-36 General Health Assessment Questionnaire (Overall Score) From Baseline to 2 Years
Overall assessment of general health as determined by scoring use an SF-36 Questionnaire (Range 0-100 with higher scores better - indicating less disability)
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2010 (estimated)
- Study startMay 2011
- Primary completionOct 2013
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, KneeStudies 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kolon TissueGene, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael A Mont, MD, Principal investigator, Sinai Hospital of BaltimoreDavid W Romness, MD, Principal investigator, Commonwealth Orthopedics, Virginia Hospital Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01221441
- Sponsor's protocol ID
- TGC09201
- Status last verified
- Jan 2016
- First submitted
- 13 Oct 2010
- Last updated
- 15 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Guermazi A, Kalsi G, Niu J, Crema MD, Copeland RO, Orlando A, Noh MJ, Roemer FW. Structural effects of intra-articular TGF-beta1 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial. BMC Musculoskelet Disord. 2017 Nov 16;18(1):461. doi: 10.1186/s12891-017-1830-8.
PubMed 29145839Cherian JJ, Parvizi J, Bramlet D, Lee KH, Romness DW, Mont MA. Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-beta1 in patients with grade 3 chronic degenerative joint disease of the knee. Osteoarthritis Cartilage. 2015 Dec;23(12):2109-2118. doi: 10.1016/j.joca.2015.06.019. Epub 2015 Jul 16.
PubMed 26188189
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Determine the Efficacy and Safety of Allogeneic Human Chondrocytes Expressing TGF-β1 (TissueGene-C) in Patients With Grade 3 Chronic Degenerative Joint Disease of the Knee
- ClinicalTrials.gov ID
- NCT01221441
- Acronym / sponsor ID
- TGC09201
- Conditions
- Osteoarthritis, Knee
- Keywords
- Cartilage, Knee, Osteoarthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Kolon TissueGene, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 15 Oct 2010 (estimated)
- Results
- Posted 15 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if we can safely regenerate cartilage without invasive surgery using a biologic product called TissueGene-C.
Detailed description
Protocol TGC09201 is a multi-center, double-blind, placebo-controlled, randomized study. A total of one hundred (100) adults with grade 3 chronic degenerative joint disease (DJD) of the knee joint (as determined by radiographic examination) will be enrolled into the study. TissueGene-C will be administered intra-articularly once via x-ray guidance. TissueGene-C will be administered at a dose of 3 x 10e7 cells. Patients receiving control treatment will receive a single normal saline injection.
The objectives of this study are to:
- Evaluate the efficacy of TissueGene-C with regard to knee functionality and symptoms of knee osteoarthritis including pain.
- Evaluate the safety of administration of a single intra-articular dose of TissueGene-C as evidenced by observation of the injection site for irritation or other abnormalities, the incidence and severity of adverse events, and the changes in physical examination findings and laboratory tests, including immune analyses.
- Evaluate the incidence and dose of analgesia and/or anti-inflammatory medication.
- Evaluate the regeneration of hyaline cartilage as determined by 3T magnetic resonance imaging (MRI).
- Evaluate distribution of hChonJb#7 cells out of the injection site.
- Evaluate the efficacy of TissueGene-C by evaluating the need for total knee arthroplasty after treatment
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TissueGene-C | Experimental | Biological: TissueGene-CTissueGene-C at 3 x 10e7 cells per injection (intraarticular) |
| Placebo Control | Placebo comparator | Drug: Normal SalineNormal Saline injection |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or Female subject
- Age 18 to 70 years
- In general good health as evidenced by physical examination, normal hematology, serum chemistry, and urinalysis screening laboratory results, and a negative history of significant organ system disorders. All laboratory values must be within 20% of normal ranges.
- Patients with Grade 3 chronic osteoarthritis of the knee as determined by the Radiographic Criteria of Kellgren and Lawrence.
- Symptom of pain for more than four (4) consecutive months and intensity of ≥ 40 and ≤ 90 on the 100-mm scale.
Key exclusion criteria (13 listed)
- Age 71 or older
- Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results.
- Patients taking non-steroidal anti-inflammatory medications within 14 days of baseline visit unless washed out as per section 3.6.4 above.
- Patients taking steroidal anti-inflammatory medications within 2 months of baseline visit.
- Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug test at the time of screening.
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 |
|---|---|---|
| TissueGene-CAlso: TG-CSingle intraarticular injection at 3 x 10e7 cells | Biological | TissueGene-C |
| Normal SalineAlso: 0.9% SalineSingle intraarticular injection of normal saline as a placebo control | Drug | Placebo Control |
Primary outcome
Change From Baseline in the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 1 Year
Time frame: 1 Year
Symptoms, pain and function of the knee joint determined and scored using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation (Total Score, range 0-100 with higher scores better). Linear mixed model used for analysis.
Change From Baseline in Visual Analog Scale (VAS) Score at 1 Year
Time frame: 1 Year
Reduction in pain as measured by a 100 mm visual analog scale (0= no pain; 100 = extreme pain) from Baseline to 1 Year. Linear mixed model used for analysis.
11 secondary outcomes
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 Years
Time frame: 2 Years
Change From Baseline in Articular Cartilage Damage in the Knee as Determined by the Lysholm Knee Score at 2 Years
Time frame: 2 Years
Comparative Evaluation of Knee Magnetic Resonance Images (MRIs) From Baseline to 1 Year
Time frame: 1 Year
Change in Pain Severity From Baseline to 2 Years as Assessed by Questionnaire
Time frame: 2 Years
Number of Participants With Change in Pain Severity Measured by Incidence and Dose of Analgesia
Time frame: 2 Years
Change From Baseline in Knee Function as Determined by the Lower Extremity Functional Scale at 2 Years
Time frame: 2 Years
The Incidence of Total Knee Arthroplasty
Time frame: 2 Years
The Number of Patients Experiencing Injection Site Reactions Related to Treatment
Time frame: 2 Years
The Incidence and Severity of Adverse Events in Treated Patients
Time frame: 2 Years
Number of Participants With Adverse Events Due to Clinically Significant Changes in Hematology and Urinalysis Tests
Time frame: 2 Years
Change in SF-36 General Health Assessment Questionnaire (Overall Score) From Baseline to 2 Years
Time frame: 2 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29145839Guermazi A, Kalsi G, Niu J, Crema MD, Copeland RO, Orlando A, Noh MJ, Roemer FW. Structural effects of intra-articular TGF-beta1 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial. BMC Musculoskelet Disord. 2017 Nov 16;18(1):461. doi: 10.1186/s12891-017-1830-8.
- Derived from this study: PubMed 26188189Cherian JJ, Parvizi J, Bramlet D, Lee KH, Romness DW, Mont MA. Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-beta1 in patients with grade 3 chronic degenerative joint disease of the knee. Osteoarthritis Cartilage. 2015 Dec;23(12):2109-2118. doi: 10.1016/j.joca.2015.06.019. Epub 2015 Jul 16.
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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.
Michael A Mont, MD principal investigator
Sinai Hospital of Baltimore
David W Romness, MD principal investigator
Commonwealth Orthopedics, Virginia Hospital Center
5 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 TissueGene-C and Normal Saline in people with Osteoarthritis, Knee, run by Kolon TissueGene, Inc. at 5 sites in United States.
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 9 inclusion and 13 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 15 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 15 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 From Baseline in the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 1 Year (time frame: 1 Year). The study lists 2 primary outcomes in all. 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 NCT01221441, 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 15 Feb 2016.