Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06606561
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-17
Brief Title:
NANOVAE to Treat Knee Osteoarthritis KOA
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Phase III Randomized Double Blinded Placebo Controlled Trial to Evaluate the Safety and Potential Efficacy of NANOVAE Injected Intra-Articular in Patients Suffering with Knee Osteoarthritis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The below summarizes relevant information for investigators to consider the use of Allogenic Human Amniotic Fluid product in a clinical protocol detailing study design and conduct for a phase III 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
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
Detailed Description:
The investigational product being assessed in this trial is called NANOVAE which is a biologic derived from human amniotic fluid HAF that is allogenic and acellular HAF contains a wide range of growth factors cytokines chemokines and extracellular vesiclesnanoparticles obtained from perinatal tissue These components contribute to the regenerative potential of HAF and make it a promising option for regenerative medicine applications particularly in knee osteoarthritis KOA Studies have demonstrated that the extracellular vesicles found in HAF including exosomes have the ability to promote chondrogenesis and reduce inflammation which are crucial processes in reversing the progression of KOA Additionally these vesicles have shown to stimulate cartilage regeneration addressing the impaired cartilage repair typically observed in OA Therefore the administration of HAF-derived products has the potential to slow down the degenerative process and promote cartilage repair in patients with KOA The growth factors and cytokines present in HAF may also help alleviate the inflammatory response observed in the knee joint a characteristic feature of KOA These anti-inflammatory properties combined with the regenerative capabilities of the extracellular vesicles make HAF an appealing candidate for the treatment of KOA
Numerous clinical studies registered under ClinicalTrialsgov have provided evidence of the safety and effectiveness of HAF products in joint therapies The use of HAF for treating OA holds immense potential due to its array of growth factors anti-inflammatory mediators and medicinal signaling cells which continue to undergo rapid advancements In a non-FDA review study a double-blinded controlled trial was conducted comparing the treatment of OA with freshly collected amniotic fluid and steroids The results revealed a significant improvement in the Visual Analog Scale VAS after three months of treatment with continuous improvement in VAS after six months in both groups However the group receiving freshly collected amniotic fluid exhibited greater improvement These findings strongly support the potential of this novel HAF therapy for advanced OA as it proved to be superior and longer lasting compared to conventional therapies commonly practiced Further research both in terms of basic science and clinical investigations is warranted to gain a better understanding of the anti-inflammatory properties of amniotic fluid and determine the most efficacious amniotic fluid product for symptomatic OA
NANOVAE is a filtered form of HAF human amniotic fluid that utilizes the wide range of nanoparticles cytokines and growth factors present in the fluid which play vital roles in fetal development and maturation HAF is a rich source of collagen substrates growth factors amino acids polyamines lipids carbohydrates cytokines and extracellular matrix molecules like hyaluronic acid and fibronectin as well as cells These components greatly contribute to tissue protection and repair Extensive research has demonstrated the antimicrobial immunomodulatory and growth-promoting properties of HAF The antimicrobial antiviral and antifungal effects of HAF have been established through the identification of various components such as lysozyme peroxidase transferrin β-lysin immunoglobulins and zinc-peptide complexes within the fluid The immunomodulatory functions of HAF have been observed in its ability to suppress alloreactive responses and downregulate Th1 and Th2 cytokines
NANOVAEs extracellular vesicle EV fraction consists of several cytokines chemokines and growth factors that are associated with functions such as host defense anti-inflammatory response angiogenesis and cartilage repair The concentration of nanoparticles in the final product has been consistently demonstrated through nanoparticle analysis using the ZetaView Quatt nanoparticle analyzer This analysis reveals a range of particles with an average mode particle size of 964 nM which aligns with the expected size of exosomes ranging between 50-200 nm in diameter
Objectives
Primary Objective To demonstrate the safety of NANOVAE administered intraarticular in subjects with KOA by measuring the 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 eg stroke or non-fatal pulmonary embolism Event resulting in persistent or significant disabilityincapacity Event resulting in death
Secondary Objective To demonstrate the potential efficacy of NANOVAE by measuring the following clinical response changes from baseline to 12 months after injection Time Frame Month 1 3 6 and 12 after infusions
Change in single leg stance test Change in Timed Up and Go test to assess fall risk Change in Western Ontario and McMaster Universities Osteoarthritis WOMAC Index five items for pain two for stiffness and seventeen for function
Change in range of motion assessed by goniometer measurements Change in serum andor synovial biomarkers between the timepoints of Day 0 and the 3-month visit
Design and Investigational Plan A total of 24 subjects meeting all inclusionexclusion 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 11 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 will be obtained from healthy donors and manufactured by the Nova Vita Laboratories processing lab
Group 1 Open Label A total of eight subjects will be treated to assess safety prior to enrolling Group 2 Safety will be assessed at seven-day intervals for the 8 subjects in Group 1 staggered by 5 days after receiving the dose of NANOVAE
Dose 2 mL of NANOVAE on Day 0 containing 10 x 10¹¹ to 90 x 10¹¹ particlesml Product will be administered directly without any dilution
After these 8 subjects complete the 5-day safety assessment the safety report will be presented to the DSMB with representative data to determine the safety status of receiving one dose of NANOVAE Once the treatment of Group 1 has been determined to be safe the enrollment of Group 2 will begin
Group 2 Randomized double-blinded placebo control A 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 particlesml The ratio is 11 for a total of 16 subjects in Group 2 Product will be administered directly without any dilution
Sample Size amp Study Population A total of 24 adult patients will be chosen from the population of adults between the ages of 21 to 75 diagnosed with KOA who meet inclusion criteria
Route of Administration Intra-articular Injections
Study Duration and Study Follow-Up 12 months total duration
Day 0 and 15 - Intraarticular Injection and observational follow-up Days 1 and 7 after dose of NANOVAE or placebo - Observational follow-up via phone call telehealth or in-person visit
Months 1 3 6 and 12 - Observational follow-up visits per protocol design
Numerous clinical studies registered under ClinicalTrialsgov have provided evidence of the safety and effectiveness of HAF products in joint therapies The use of HAF for treating OA holds immense potential due to its array of growth factors anti-inflammatory mediators and medicinal signaling cells which continue to undergo rapid advancements In a non-FDA review study a double-blinded controlled trial was conducted comparing the treatment of OA with freshly collected amniotic fluid and steroids The results revealed a significant improvement in the Visual Analog Scale VAS after three months of treatment with continuous improvement in VAS after six months in both groups However the group receiving freshly collected amniotic fluid exhibited greater improvement These findings strongly support the potential of this novel HAF therapy for advanced OA as it proved to be superior and longer lasting compared to conventional therapies commonly practiced Further research both in terms of basic science and clinical investigations is warranted to gain a better understanding of the anti-inflammatory properties of amniotic fluid and determine the most efficacious amniotic fluid product for symptomatic OA
NANOVAE is a filtered form of HAF human amniotic fluid that utilizes the wide range of nanoparticles cytokines and growth factors present in the fluid which play vital roles in fetal development and maturation HAF is a rich source of collagen substrates growth factors amino acids polyamines lipids carbohydrates cytokines and extracellular matrix molecules like hyaluronic acid and fibronectin as well as cells These components greatly contribute to tissue protection and repair Extensive research has demonstrated the antimicrobial immunomodulatory and growth-promoting properties of HAF The antimicrobial antiviral and antifungal effects of HAF have been established through the identification of various components such as lysozyme peroxidase transferrin β-lysin immunoglobulins and zinc-peptide complexes within the fluid The immunomodulatory functions of HAF have been observed in its ability to suppress alloreactive responses and downregulate Th1 and Th2 cytokines
NANOVAEs extracellular vesicle EV fraction consists of several cytokines chemokines and growth factors that are associated with functions such as host defense anti-inflammatory response angiogenesis and cartilage repair The concentration of nanoparticles in the final product has been consistently demonstrated through nanoparticle analysis using the ZetaView Quatt nanoparticle analyzer This analysis reveals a range of particles with an average mode particle size of 964 nM which aligns with the expected size of exosomes ranging between 50-200 nm in diameter
Objectives
Primary Objective To demonstrate the safety of NANOVAE administered intraarticular in subjects with KOA by measuring the 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 eg stroke or non-fatal pulmonary embolism Event resulting in persistent or significant disabilityincapacity Event resulting in death
Secondary Objective To demonstrate the potential efficacy of NANOVAE by measuring the following clinical response changes from baseline to 12 months after injection Time Frame Month 1 3 6 and 12 after infusions
Change in single leg stance test Change in Timed Up and Go test to assess fall risk Change in Western Ontario and McMaster Universities Osteoarthritis WOMAC Index five items for pain two for stiffness and seventeen for function
Change in range of motion assessed by goniometer measurements Change in serum andor synovial biomarkers between the timepoints of Day 0 and the 3-month visit
Design and Investigational Plan A total of 24 subjects meeting all inclusionexclusion 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 11 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 will be obtained from healthy donors and manufactured by the Nova Vita Laboratories processing lab
Group 1 Open Label A total of eight subjects will be treated to assess safety prior to enrolling Group 2 Safety will be assessed at seven-day intervals for the 8 subjects in Group 1 staggered by 5 days after receiving the dose of NANOVAE
Dose 2 mL of NANOVAE on Day 0 containing 10 x 10¹¹ to 90 x 10¹¹ particlesml Product will be administered directly without any dilution
After these 8 subjects complete the 5-day safety assessment the safety report will be presented to the DSMB with representative data to determine the safety status of receiving one dose of NANOVAE Once the treatment of Group 1 has been determined to be safe the enrollment of Group 2 will begin
Group 2 Randomized double-blinded placebo control A 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 particlesml The ratio is 11 for a total of 16 subjects in Group 2 Product will be administered directly without any dilution
Sample Size amp Study Population A total of 24 adult patients will be chosen from the population of adults between the ages of 21 to 75 diagnosed with KOA who meet inclusion criteria
Route of Administration Intra-articular Injections
Study Duration and Study Follow-Up 12 months total duration
Day 0 and 15 - Intraarticular Injection and observational follow-up Days 1 and 7 after dose of NANOVAE or placebo - Observational follow-up via phone call telehealth or in-person visit
Months 1 3 6 and 12 - Observational follow-up visits per protocol design
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None