NANOVAE for Knee Osteoarthritis

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Nova Vita Laboratory

No Placebo Group

Trial Summary

What is the purpose of this trial?The below summarizes relevant information for investigator(s) to consider the use of Allogenic Human Amniotic Fluid product in a clinical protocol detailing study design and conduct for a phase I/II randomized, double-blinded, placebo-controlled clinical trial to evaluate the safety and potential efficacy of NANOVAE injected intra-articularly in patients suffering from knee osteoarthritis. The IB will be reviewed annually and amended when further information becomes available. Osteoarthritis (OA) is a degenerative disease of the joints that affects millions of people worldwide, yet its exact causes are not fully understood. Middle-aged to elderly individuals are often the most impacted by OA, which primarily affects the knee, hip, spine, and joints in the fingers. Among these, knee osteoarthritis (KOA) is the most common form, causing pain, stiffness, and reduced functionality, and it is a major contributor to chronic bone and muscle pain. It is also a leading cause of disability in adults who are not living in institutions. Treatment for KOA is challenging due to its resistance to medications, procedures, and surgeries. The primary objective is to alleviate pain and enhance overall function. However, since there is currently no cure for OA, the need for an effective therapy remains urgent. Healthcare professionals often encounter patients whose pain may result from an inflammatory response triggered by injury or disease. Research suggests that regenerative medicine, utilizing techniques like stem cells, platelet-rich plasma (PRP), amniotic fluid, and cytokine modulation, holds promise for treating KOA. OA is associated with an increase in pro-inflammatory substances such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMPs), nitric oxide (NO), reactive oxygen species (ROS), and cytokine-inducible cyclooxygenase-2 (COX-2). These inflammatory agents affect various cell types within the affected joints, including chondrocytes, osteoblasts, osteoclasts, synoviocytes, and macrophages. Some miRNAs, which are downregulated in OA, have been identified as protective factors. For example, miR-130 helps regulate TNF-α levels, while miR-149 controls several inflammatory cytokines such as IL-1, IL-6, and TNF-α. The breakdown of the cartilage matrix is a key characteristic of OA. MMP-13, a member of the MMP family, plays a significant role in degrading the collagen network during OA development. Several miRNAs, including miR-27b, miR-27a, miR-148a, miR-320, miR-127-5p, and miR-411, are downregulated in OA and target the mRNA of this proteinase. It is important to note that a single miRNA can regulate multiple target genes associated with OA progression. For instance, miR-105 and miR-148, both downregulated in OA, target genes such as Runx2, ADAMTS4, ADAMTS5, ADAMTS7, ADAMTS12, MMP-13, and COL10, implying their potential protective roles. Several studies have shown a link between certain miRNAs, aging, and the progression of OA. For example, miR-320c is downregulated in aging OA samples and regulates ADAMTS5, suggesting that this miRNA may serve as a protective factor by enhancing chondrogenesis.

Eligibility Criteria

This trial is for individuals with knee osteoarthritis, a joint condition causing pain and stiffness. Participants should be middle-aged or older as this group commonly experiences OA. Specific eligibility criteria are not provided, but typically include having symptoms of KOA and being in generally stable health.

Inclusion Criteria

Subjects must be available for all specified assessments at the study site through the completion of the study

Patient may be eligible for treatment of both knees if criteria is met for both

Study subjects must be willing to 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

+8 more

Exclusion Criteria

I am not planning to use steroids during the study, except for COVID-19 or a non-arthritic flare-up.

I have received a solid organ transplant and have experienced rejection.

I haven't had a hyaluronic acid injection in the last 6 months.

+25 more

Participant Groups

The study tests NANOVAE (Allogenic Human Amniotic Fluid) against a placebo (0.9% Sodium Chloride Injection). It's a phase I/II trial to assess safety and potential effectiveness when injected into the knee joint of those with osteoarthritis, comparing outcomes between the two groups.

2Treatment groups

Experimental Treatment

Group I: Group 2 (Randomized, double blinded placebo control)Experimental Treatment2 Interventions

Total of sixteen subjects will be randomized to either receive two doses of NANOVAE via intraarticular injections or receive two doses of a placebo. Dose - 2 mL of NANOVAE or placebo on day 0 and day 15, containing 1 x 1011 particles/ml. The ratio is 1:1 for a total of 16 subjects in the Group 2. Product will be administered directly without any dilution.

Group II: Group 1 (Open Label)Experimental Treatment1 Intervention

A total of eight subjects will be treated to assess safety prior to enrolling Group 2. We propose to assess the safety of 8 subjects in Group 1 at seven-day intervals. Each subject in Group 1 will be staggered by 5 days after receiving the dose of NANOVAE. Dose - 2 mL of NANOVAE on day 0 containing 1.0 x 1011 to 9.0 x 1011 particles/ml. Product will be administered directly without any dilution.