NANOVAE to Treat Knee Osteoarthritis (KOA)

NCT06606561 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NVL-2024-257
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Knee Osteoarthritis

Keywords

Knee Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NANOVAE administered intraarticular in subjects

  To demonstrate the safety of NANOVAE administered intraarticular in subjects with KOA by measuring incidence of any of the following treatment-emergent adverse events (TE-AEs) and treatment-emergent serious adverse events (TE-SAEs) within the first 30 days of injection: * Occurrence of adverse events related to the therapy within 30 days of NANOVAE treatment. * Life-threatening event (e.g., stroke or non-fatal pulmonary embolism). * Event resulting in persistent or significant disability/incapacity. * Event resulting in death.

  30 Days

Secondary Outcomes (5)

• Change in Single Leg Stance Test

  Baseline, Month 1, 3, 6, and 12 after infusions

• Change in "Timed Up and Go" Test

  Baseline, Month 1, 3, 6, and 12 after infusions

• Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)

  Baseline, Month 1, 3, 6, and 12 after infusions

• Change in Serum and/or Synovial Biomarkers

  Baseline, Month 1, 3, 6, and 12 after infusions

• Change in Range of Motion (ROM)

  Baseline, Month 1, 3, 6, and 12 after infusions

Study Arms (2)

Group 1 (Open Label)

EXPERIMENTAL

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.

Drug: NANOVAE - Acellular Allogenic Human Amniotic Fluid (hAF)

Group 2 (Randomized, double blinded placebo control)

EXPERIMENTAL

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.

Drug: NANOVAE - Acellular Allogenic Human Amniotic Fluid (hAF); Drug: 0.9% Sodium Chloride Injection, USP

Interventions

NANOVAE - Acellular Allogenic Human Amniotic Fluid (hAF) DRUG

A total of 24 subjects meeting all inclusion/exclusion criteria will be divided into two groups. Group 1 will be an open-label lead-in phase. Group 2 will be a randomized, double-blinded, placebo-controlled cohort. Group 1 will receive one dose of 2ml of NANOVAE, and Group 2, in a randomized and double-blinded fashion, will receive two doses of 2ml NANOVAE. Neither the patients nor the researchers will know who is getting the placebo and who is getting the NANOVAE; only the product manufacturing staff will be unblinded. The ratio of placebo to NANOVAE is 1:1 for a total of 16 subjects in Group 2. Only the knee with the more severe symptoms of OA will be treated. The allogenic-HAF

Group 1 (Open Label); Group 2 (Randomized, double blinded placebo control)

0.9% Sodium Chloride Injection, USP DRUG

In lieu of AF, the saline for injection will be used as a placebo. Vials acquired from the manufacturer is pipetted into glass vials, stoppered, capped, placed in labeled header foil pouches, and sealed. These are transferred to a quarantine freezer to await post-production testing.

Also known as: Placebo

Group 2 (Randomized, double blinded placebo control)

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age eligible for study: 21 to 75 years
• Gender eligible for study: All
• 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.
• Subjects have a diagnosis of OA in at least one knee defined as Grade II or III on Kellgren-Lawrence (K-L) grading scale which is confirmed by posterior-anterior, weight-bearing, fixed flexion radiography with 10o caudal beam angulation.
• Subjects with VAS pain score ≥40 mm on screening day will be included.
• Subjects had one or more of the following SOC treatments within the previous 12 months will be included:
• weight loss
• physical therapy
• anti-inflammatory medications - oral, injections and topical
• Body mass index (BMI) \< 45kg/m2
• Subjects must be available for all specified assessments at the study site through the completion of the study.
• For Women of Child-Bearing Potential (WOCBP) only, willingness to use FDA-recommended birth control until 6 months post treatment. The FDA-approved and cleared methods for birth control are listed below:
• Permanent Sterilization
• Long-Acting Reversible Contraceptives (LARC)
• Contraceptive Injection

You may not qualify if:

• Subjects have evidence of significant and unstable cardiac dysfunction, e.g. acute myocardial infarction and hypertension with uncontrolled blood pressure over 140/90 will be excluded.
• Subjects at screening with white blood cell count \< 4 x 109 cells/L, hematocrit \<30%, and platelets \<150 x 109 /L will be excluded.
• Subjects with poorly controlled diabetes (hemoglobin A1C \> 7.5 or fasting blood glucose of \>200) in last 6 months will be excluded.
• Individuals on dialysis or uncontrolled renal disease will be excluded.
• Subjects with abnormal hematology, serum chemistry, or urinalysis screening laboratory results will be excluded.
• Subjects with history of, or ongoing, autoimmune disorder that requires treatment with an immunosuppressive medication will be excluded.
• Subjects had knee surgery on the targeted knee within 12 months prior to screening and /or planned knee surgery during the study will be excluded.
• Subjects have a body mass index greater than 45 kg/m2 will be excluded.
• Subjects whose knee pain is caused by, (i) diffuse edema, extra articular causation (ii) displaced meniscus tear, (iii) full thickness articular cartilage lesion greater than 1 cm in any direction, or (iv) osteochondritis dissecans will be excluded.
• Subjects have rheumatoid arthritis, psoriatic arthritis, or have been diagnosed with any other auto-immune disorders that could be the cause of their knee pain will be excluded.
• Subjects which have evidence or history of malignancy except those who are successfully treated in situ or basal cell skin cancers will not be excluded.
• Subjects with a history of clotting disorder, anticoagulation therapy that cannot be stopped as prior to infusion will be excluded.
• Subjects have evidence of liver dysfunction manifested as alkaline phosphatase greater than 345 u/L, total bilirubin greater than 1.65 mg/dL, ALT greater than 275 units/L and/or AST great than 240 units/L will be excluded.
• Subjects have or had an active infection requiring systemic antibiotics within 2 weeks on enrollment in the study will be excluded.
• Subjects currently taking anticoagulant therapy (excluding Plavix or Aspirin) will be excluded.

Sponsors & Collaborators

• Nova Vita Laboratory: lead

Study Sites (1)

Bluetail Medical Group

Chesterfield, Missouri, 63005, United States

Location

Related Publications (1)

• Kohn MD, Sassoon AA, Fernando ND. Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis. Clin Orthop Relat Res. 2016 Aug;474(8):1886-93. doi: 10.1007/s11999-016-4732-4. Epub 2016 Feb 12. No abstract available.

  PMID: 26872913 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

David Crane, MD

CONTACT

(636) 778-2900; David@novavitalabs.com

Trillitye Paullin, PhD

CONTACT

(984) 569-2483; Trill@novavitalabs.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A total of 24 subjects meeting all inclusion/exclusion criteria will be divided into two groups. Group 1 will be an open-label lead-in phase. Group 2 will be a randomized, double-blinded, placebo-controlled cohort. Group 1 will receive one dose of 2ml of NANOVAE, and Group 2, in a randomized and double-blinded fashion, will receive two doses of 2ml NANOVAE. Neither the patients nor the researchers will know who is getting the placebo and who is getting the NANOVAE; only the product manufacturing staff will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: September 23, 2024
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)