Clinical trial NCT04711304: Evaluation of Safety and Efficacy of Wharton's Jelly Compared to Hyaluronic Acid and Saline for Knee Osteoarthritis.
Official title: A Randomized, Controlled, Single-blind, Multi-center Trial to Evaluate the Safety and Efficacy of Intraarticular Injection of Umbilical Cord Derived Wharton's Jelly Compared to Hyaluronic Acid and Saline for Knee Osteoarthritis.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Osteoarthritis, Knee
Keywords: Knee Osteoarthritis, Umbilical Cord, Wharton's Jelly
Lead sponsor: BioIntegrate
Sponsor class: INDUSTRY
First posted: 2021-01-15
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of intraarticular injection of umbilical cord derived Wharton's Jelly compared to hyaluronic acid and saline for treatment of knee osteoarthritis symptoms.

Detailed description: Osteoarthritis (OA) is the most common joint disorder in the United States (US), affecting approximately 12% (\~30 million) of US adults aged between 25 and 74 years. By 2030, the number of US adults with arthritis is expected to reach 67 million leading to continuous increase in number of total knee replacement surgeries. While total knee replacement surgeries have shown advantages, avoiding or delaying surgery appears desirable, both from medical and health care system perspective. Lowering the number of total knee replacement surgeries will also lead to a reduced number of costly revision surgeries. Published studies have also demonstrated that the outcomes after total knee replacement surgeries for patients with Grade II or III knee OA (on Kellgren-Lawrence scale) are worse compared to patients with Grade IV OA. Additionally, conventional treatment modalities including activity modification, physical therapy, pharmacological agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, viscosupplementation and narcotics have limitations and potential side effects. Thus, there is a need for alternative intervention for patients with Grade II or III knee OA.

Interest in the use of biologics for regenerative medicine applications has increased over the last decade. To be compliant in the United States (U.S.), biologics that adhere to the U.S. Food and Drug Administration (FDA) regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/P's) regulated under title 21, part 1271 of the Code of Federal Regulations (CFR) must meet all the conditions under section 361 of Public Health Safety (PHS) Act to be regulated solely under this section. According to this regulation, HCT/P's must meet the criteria of being minimally manipulated, for homologous use only, not to be combination products, to have no systemic effect, and to be non-dependent on the metabolic activity of the living cells. Despite increased use, there is insufficient literature assessing the amount of growth factors (GF), cytokines (CK), hyaluronic acid (HA) and extracellular vesicles (EV) including exosomes present in these products, and more specifically, umbilical cord derived Wharton's Jelly. In addition, there is limited or no literature assessing the safety and efficacy of umbilical cord derived Wharton's Jelly products via a randomized, controlled, multi-center study.

To address the insufficient literature assessing the presence and quantity of GF, CK, HA and EV including exosomes, investigators formulated a novel umbilical cord derived Wharton's Jelly product and evaluated it for the presence of these factors. The results from this study demonstrated that the essential components of regenerative medicine, namely GF, CK, HA and EV, are all present in large quantities in the formulated Wharton's Jelly. This study was an essential preliminary step to better characterize this Wharton's Jelly formulation before performing clinical trials to determine safety and efficacy of this novel formulation for regenerative medicine applications including for providing symptomatic relief to patients with Grade II or III knee OA.

The goal of the proposed study is to evaluate the safety and efficacy of intraarticular injection of umbilical cord derived Wharton's Jelly for treatment of knee osteoarthritis symptoms. Investigators hypothesize that there will be no difference in patients receiving injection of umbilical cord derived Wharton's Jelly, HA or saline with respect to safety. Investigators also hypothesize that patients receiving intraarticular injection of Wharton's Jelly will show an improvement in their overall satisfaction, Numeric Pain rating Scale (NPRS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and cartilage formation over a period of 1 year compared to the baseline visit. Our null hypothesis is that there is no difference in patients receiving either Wharton's Jelly, hyaluronic acid or saline; and no difference between the baseline and after-treatment within each treatment group over a period of 1 year.

Eligibility criteria: Inclusion Criteria:

1. Patients must be 18 years or older.
2. Must have a body mass index (BMI) of \< 50Kg/m2.
3. Must be able to comply with the requirements of study visits.
4. Diagnosed with mild to moderate knee osteoarthritis (OA) in one knee only - Grade 2 or 3 on the Kellgren Lawrence (KL) grading scale.
5. Pain score of 4 or more on the NPRS (on scale of 0 to 10).
6. Female patients were abstinent, surgically sterilized or postmenopausal.
7. Premenopausal females with negative pregnancy test, and who does not anticipate pregnancy and will actively practice an accepted contraceptive method for the duration of study.
8. Males with premenopausal female partners, will take contraceptive measures for the duration of study.
9. Be willing and capable of giving written informed consent to participate in this clinical study.
10. Be willing and capable of complying with study-related requirements, procedures and visits.

Exclusion Criteria:

1. Patients who have taken any pain medications including NSAIDs within 2 weeks, prior to the study injection date, regularly use anticoagulants, substance abuse history, and/or failure to agree not to take any knee-symptom modifying drugs during the course of the study without discussing and reporting the use to site principal investigator and study team.
2. Patients who are positive on special tests and stability tests on the physical exam case report form.
3. Patients with intraarticular injection of any drug including corticosteroids, viscosupplementation in the index knee in last 3 months.
4. Patients with index knee surgery within last 6 months.
5. Patients with traumatic injury to index knee within last 3 months.
6. Patients with planned elective surgery during the course of the study.
7. Patients with organ or hematologic transplantation history, rheumatoid arthritis or other autoimmune disorders.
8. Patients on immunosuppressive medication/treatment, diagnosis of non-basal cell carcinoma within last 5 years.
9. Patients with knee infection or who used antibiotics for knee infection within last 3 months.
10. Patients who participated in another clinical trial or treatment with any investigational product within last 30 days prior to inclusion in the study.
11. Female patients who are breast feeding or are pregnant or desire to be pregnant during the course of the study.
12. Patients with contraindication to X-ray or MRI imaging.
13. Patients with serious neurological, psychological or psychiatric disorders.
14. Patients with other medical conditions determined by site principal investigator as interfering with the study.
15. Patients with an injury or disability claim under current litigation or pending or approved workers' compensation claim.

Primary outcomes:
measure: Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: Immediately after injection
measure: Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 24hours after injection
measure: Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 48hours after injection
measure: Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 1week after injection
measure: Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 6weeks after injection
measure: Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 3Months after injection
measure: Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 6Months after injection
measure: Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 1Year after injection
measure: Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 1week after injection
measure: Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 6weeks after injection
measure: Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 3Months after injection
measure: Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 6Months after injection
measure: Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: 1Year after injection
measure: Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: Change from baseline to 3Months after injection
measure: Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: Change from baseline to 6Months after injection
measure: Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly
timeFrame: Change from baseline to 1Year after injection
Secondary outcomes:
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Change from baseline to immediately after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and immediately after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Change from baseline to 24hours after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 24hours after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Change from baseline to 48hours after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 48hours after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Change from baseline to 1week after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 1week after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Change from baseline to 6weeks after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 6weeks after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Change from baseline to 3Months after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 3Months after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Change from baseline to 6Months after injection
measure: Change in patient reported outcome measures, Numeric Pain Rating Scale
timeFrame: Change from baseline to 1year after injection
measure: Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
timeFrame: Change from baseline to 1week after injection
measure: Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 1week after injection
measure: Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
timeFrame: Change from baseline to 6weeks after injection
measure: Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 6weeks after injection
measure: Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
timeFrame: Change from baseline to 3Months after injection
measure: Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
timeFrame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 3Months after injection
measure: Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
timeFrame: Change from baseline to 6Months after injection
measure: Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
timeFrame: Change from baseline to 1Year after injection
measure: Cartilage Formation
timeFrame: Change from baseline to 1year after injection
Other outcomes:
Locations:
Study officials:
affiliation: El-Amin Orthopaedic & Sports Medicine Institute
name: Saadiq F. El-Amin III, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: BioIntegrate
name: Ashim Gupta, PhD, MBA
role: STUDY_DIRECTOR
References:
citation: Gupta A, Maffulli N, Rodriguez HC, Carson EW, Bascharon RA, Delfino K, Levy HJ, El-Amin SF 3rd. Safety and efficacy of umbilical cord-derived Wharton's jelly compared to hyaluronic acid and saline for knee osteoarthritis: study protocol for a randomized, controlled, single-blind, multi-center trial. J Orthop Surg Res. 2021 May 31;16(1):352. doi: 10.1186/s13018-021-02475-6.