NANOVAE for Knee Osteoarthritis

Overseen By Trillitye Paullin, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nova Vita Laboratory

Must not be taking: Anticoagulants, Immunosuppressives, Systemic steroids

Disqualifiers: Cardiac dysfunction, Diabetes, Autoimmune disorders, Liver dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking prescription or over-the-counter pain medication for osteoarthritis for 7 days before any visit. However, you can continue taking medications for other conditions, except those listed under 'Concomitant Medication.'

What data supports the effectiveness of the treatment NANOVAE for knee osteoarthritis?

Research on similar treatments, like amniotic suspension allografts, shows they can reduce pain and improve function in people with knee osteoarthritis. These treatments contain substances that help reduce inflammation and promote healing, which may explain their effectiveness. ^{1 2 3 4 5}

Is NANOVAE safe for treating knee osteoarthritis?

Research on treatments similar to NANOVAE, like amniotic suspension allografts, shows they are generally safe for humans. Some studies reported no significant side effects, while others noted mild pain after injection that lasted a few days. ^{1 2 3 4 5}

How is the NANOVAE treatment for knee osteoarthritis different from other treatments?

NANOVAE, which uses acellular allogenic human amniotic fluid, is unique because it leverages growth factors and cytokines from placental-derived tissues to reduce inflammation and promote healing, potentially offering a regenerative approach to managing knee osteoarthritis without surgery. ^{1 2 3 5 6}

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

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open Label Safety Assessment

Group 1 subjects receive a single dose of NANOVAE and are assessed for safety at seven-day intervals

5 days

1 visit (in-person), 1 follow-up (virtual or in-person)

Randomized Treatment

Group 2 subjects receive two doses of NANOVAE or placebo, with follow-up assessments

15 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

4 visits (in-person) at Months 1, 3, 6, and 12

Treatment Details

Interventions

• NANOVAE - Acellular Allogenic Human Amniotic Fluid (hAF)

Trial Overview 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.

Participant Groups

Group I: Group 2 (Randomized, double blinded placebo control) Experimental Treatment 2 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 Treatment 1 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.

Who Is Running the Clinical Trial?

Nova Vita Laboratory

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

A feasibility study involving 6 patients with severe knee osteoarthritis showed that a single injection of human amniotic suspension allografts (ASA) was safe, with no significant adverse reactions or effects on blood cell counts and inflammatory markers over 12 months.

Patient-reported outcomes indicated a potential benefit from the ASA treatment, supporting the need for a larger placebo-controlled trial to further evaluate its efficacy in managing symptoms of knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreserved Amniotic Suspension for the Treatment of Knee Osteoarthritis. Vines, JB., Aliprantis, AO., Gomoll, AH., et al.[2017]

In a multicenter randomized controlled trial involving 200 subjects with knee osteoarthritis, amniotic suspension allograft (ASA) treatment resulted in significantly greater improvements in pain and function compared to both hyaluronic acid (HA) and saline treatments over 3 and 6 months.

Only 13.2% of patients receiving ASA reported unacceptable pain at 3 months, compared to 68.8% in the HA group and 75% in the saline group, indicating ASA's potential as an effective nonoperative management option for symptomatic knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. Farr, J., Gomoll, AH., Yanke, AB., et al.[2020]

In a rat model of knee osteoarthritis, injections of amniotic suspension allograft (ASA) significantly improved pain thresholds, gait, and overall function, indicating its potential efficacy as a nonsurgical treatment.

The study found that ASA treatment led to increased cartilage thickness and anti-inflammatory cytokines without causing adverse effects, suggesting it is a safe option for managing knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic suspension allograft improves pain and function in a rat meniscal tear-induced osteoarthritis model. Kimmerling, KA., Gomoll, AH., Farr, J., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Injectable Amniotic Membrane/Umbilical Cord Particulate for Knee Osteoarthritis: A Prospective, Single-Center Pilot Study. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Intra-Articular Injection of Amniotic Membrane and Umbilical Cord Particulate for the Management of Moderate to Severe Knee Osteoarthritis. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis-A Large Retrospective Case Series. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Cryopreserved Amniotic Suspension for the Treatment of Knee Osteoarthritis. [2017]

5. Germany pubmed.ncbi.nlm.nih.gov

A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Amniotic suspension allograft improves pain and function in a rat meniscal tear-induced osteoarthritis model. [2022]