Osteoarthritis (OA)
Conditions
Brief summary
This is a pivotal study. The study will examine the safety and efficacy of autologous adipose-derived stromal vascular fraction (SVF) cells processed with the GID SVF-2 device for pain, function and stiffness in the knees of osteoarthritic subjects.
Detailed description
Osteoarthritis is the main form of arthritis and affects over 20 million people in the United States. In the knee it can cause severe pain, reduced functionality and increased stiffness thus, a treatment that would reduce pain, increase function and reduce stiffness would be of benefit to many people. This study will collect and disassociate adipose tissue and inject the stromal vascular fraction into the knee of the same patient. The study is controlled, randomized and double-blinded with 2 SVF treatments (high and low dose) and a placebo control.
Interventions
DEVICEGID SVF-2
The GID SVF-2 device is a sterile single-use disposable canister used for harvesting, filtering, separating, and concentrating autologous stromal vascular fraction cells from adipose tissue for reintroduction to the same patient during a single surgical procedure for treatment of pain associated with joint osteoarthritis.
OTHERPlacebo
Placebo Control
Sponsors
GID BIO, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Grade II or Grade III osteoarthritis using Kellgren-Lawrence grading scale (K-L Grade) as diagnosed using weight bearing X-ray, physician review, and/or pre-op MRI. * Study Subjects must have failed a minimum of at least two conservative therapies, spanning a period of at least 3 months. * Study Subjects must be willing to voluntarily give written Informed Consent to participate in the study and sign the Health Insurance Portability and Accountability Act (HIPAA) authorization before any study procedures are performed. * Subjects will be in good health (ASA Class I-II) with a BMI \< 35. * Subjects must have continued pain in the knee despite conservative therapies for at least 3 months. * Subjects with unilateral disease must present with symptomatic knee pain using the WOMAC subscale for pain. * Subjects must speak, read and understand English. * Subjects must be reasonably able to return for multiple follow-up visits.
Exclusion criteria
* Subjects whose knee pain is caused by, (i) diffuse edema, (ii) displaced meniscus tear, (iii) lesion greater than 1 cm in any direction, or (iv) osteochondritis dissecans. * Subjects who have had surgery of either knee within 6 months prior to the screening visit. * Subjects who have had a major injury to the targeted knee within 12 months prior to enrolling in the study. * Subjects who have had an injection in either knee in the prior 3 months, including corticosteroids, viscosupplementation or platelet rich plasma (PRP). * Subjects who have gout, rheumatoid arthritis, lupus arthropathy, psoriatic arthritis, avascular necrosis, severe bone deformity, infection of the knee joint, fibromyalgia, pes anserine bursitis, or neurogenic or vascular claudication. * Subjects who have symptomatic OA of the hips, spine, or ankle that would interfere with the evaluation of the treated knee. * Subjects that are unwilling to stop taking prescription or over the counter pain medication for 7 days prior to any visit * Subjects that are allergic to lidocaine, epinephrine or valium * Subjects with a history of bleeding disorders, anticoagulation therapy that cannot be stopped as prior to injection. * Subjects with systemic immunosuppressant use within six (6) weeks from screening and subjects with HIV/viral hepatitis. * Subjects with chondrocalcinosis, Paget's disease and Villonodular synovitis * Subjects that use any form of tobacco * Women that are pregnant or planning to become pregnant during the study. * Subjects on long term use of oral steroids * History of any chemotherapy or radiation therapy of the targeted/treatment leg or adipose harvest site. * Subjects currently on worker's compensation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | up to 1 year | Subjects will be monitored for serious and device related adverse events. Baseline MRIs will be compared to 1 year for any abnormal findings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy - Percent Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score From Baseline to 6 Months | baseline and 6 months | The primary efficacy will be achieved if either dose group is shown to be superior to the placebo group at 6 months post-treatment, using the percent change in WOMAC score from baseline as the primary variable. The WOMAC score consists of 3 subscales, pain, stiffness and function. The overall score is normalized to a range of 0 to 100 points with a lower score indicating less symptoms of osteoarthritis. |
Countries
United States
Participant flow
Recruitment details
Recruitment opened April 2015 and the first subject was enrolled in the study in July 2016. Recruitment was completed in September 2017.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose SVF This group of subjects will receive a low dose of SVF (15 ± 2.5 x 10e6 SVF cells) for treatment of knee OA. | 13 |
| High Dose SVF This group of subjects will receive a high dose of SVF (30 ± 2.5 x 10e6) SVF cells for treatment of knee OA. | 13 |
| Placebo This group of subjects will receive a placebo with no SVF (0 SVF cells) for treatment of knee OA. | 13 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Elected to have total knee replacement | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Low Dose SVF | High Dose SVF | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 7.9 | 59.5 years STANDARD_DEVIATION 11.7 | 57.1 years STANDARD_DEVIATION 9.1 | 59.0 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 11 Participants | 10 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Kellgren Lawrence Osteoarthritis Grade KL Grade II | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Kellgren Lawrence Osteoarthritis Grade KL Grade III | 9 Participants | 9 Participants | 9 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 13 Participants | 12 Participants | 38 Participants |
| Region of Enrollment United States | 13 participants | 13 participants | 13 participants | 39 participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 7 Participants | 22 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 1 / 13 | 2 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
Safety - Number of Participants With Treatment-Emergent Serious Adverse Events
Subjects will be monitored for serious and device related adverse events. Baseline MRIs will be compared to 1 year for any abnormal findings.
Time frame: up to 1 year
Population: Thirty-eight subjects were monitored to 1 year. One subject was monitored for 6 weeks, when the subject withdrew from the study to receive a total knee replacement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose SVF | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | Device Related Serious Adverse Events | 0 Participants |
| Low Dose SVF | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | Serious Adverse Events | 0 Participants |
| Low Dose SVF | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | MRI abnormalities | 0 Participants |
| High Dose SVF | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | Device Related Serious Adverse Events | 0 Participants |
| High Dose SVF | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | Serious Adverse Events | 0 Participants |
| High Dose SVF | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | MRI abnormalities | 0 Participants |
| Placebo | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | Serious Adverse Events | 0 Participants |
| Placebo | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | MRI abnormalities | 0 Participants |
| Placebo | Safety - Number of Participants With Treatment-Emergent Serious Adverse Events | Device Related Serious Adverse Events | 0 Participants |
Secondary
Efficacy - Percent Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score From Baseline to 6 Months
The primary efficacy will be achieved if either dose group is shown to be superior to the placebo group at 6 months post-treatment, using the percent change in WOMAC score from baseline as the primary variable. The WOMAC score consists of 3 subscales, pain, stiffness and function. The overall score is normalized to a range of 0 to 100 points with a lower score indicating less symptoms of osteoarthritis.
Time frame: baseline and 6 months
Population: The data set was analyzed with an Intent-to-treat principle and used the last observation carried forward (LOCF) method for missing data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose SVF | Efficacy - Percent Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score From Baseline to 6 Months | 52 percentage of change in WOMAC score |
| High Dose SVF | Efficacy - Percent Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score From Baseline to 6 Months | 84 percentage of change in WOMAC score |
| Placebo | Efficacy - Percent Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score From Baseline to 6 Months | 25 percentage of change in WOMAC score |
Comparison: Data from the groups showed a strong non-normal distribution, thus non-parametric methods were used with a Bonferroni correction for multiple comparison .~Statistical significance was defined as either of the treatment groups to be superior to the placebo group.p-value: 0.023Wilcoxon (Mann-Whitney)
Comparison: Data from the groups showed a strong non-normal distribution, thus non-parametric methods were used with a Bonferroni correction for multiple comparison .~Statistical significance was defined as either of the treatment groups to be superior to the placebo group.p-value: 0.043Wilcoxon (Mann-Whitney)