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Dose Escalation Pilot Study to Evaluate the Safety of Alocyte for the Treatment of Facetogenic Back Pain

Primary Purpose

Facet Joints; Degeneration, Back Pain, Facet Joint Pain

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Alocyte low dose
Alocyte medium dose
Alocyte high dose
Sponsored by
Alimorad Farshchian
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Facet Joints; Degeneration focused on measuring Back pain, Facet joint pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: In order to be eligible to participate in this study, all individuals must meet all of the following criteria: Subjects age > 18 years at the time of signing the Informed Consent Form. Male or Female. Ability of participant to understand and the willingness to sign a written informed consent document. Facetogenic back pain diagnosed using the following diagnostic criteria Subjects who have chronic low back pain based on clinical evaluation. Pain onset at dorsal extension and release at flexion is often considered suggestive for facet pain, even if non-specific, such as maximal tenderness upon deep palpation of posterior elements. Patient with up to 5 diseased facet joints Chronic Facetogenic pain (≥ 6 months) in patients that have failed conservative management Subjects must be reasonably able to return for multiple follow-up visits. For Women of Child-Bearing Potential (WOCBP) only, willingness to use FDA-recommended birth control until 6 months post treatment. Any male subject must agree to use contraceptives and not donate sperm during the study. Exclusion Criteria: Previous surgical intervention for back pain Previous stem cell injection(s) within the last year Use of anticoagulation or NSAIDs within 5 days of the injection MRI finding of severe high-grade lumbar stenosis Leg pain exceeding back pain Pain worse with flexion maneuvers Fracture of lumbar vertebrae Inability to perform any of the assessments required for endpoint analysis. Clinically significant abnormal screening laboratory or clinical assessment values Use of medications during the early phase of treatment such as chronic narcotic use, systemic corticosteroid administration, local corticosteroid injection at facets anticoagulant therapy and viscosupplementation into facets, any investigational drug used within 3 months prior to screening or during study and surgery in the facets Subjects with serious co-morbidities are excluded. Evidence of inflammatory arthritis (example, rheumatoid arthritis and ankylosing spondylitis) or traumatic fractures, osteoarthritis, meniscoid entrapment, synovial impingement, joint subluxation, synovial inflammation, loss of cartilage, and mechanical injury. Have a clinical history of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), except curatively treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma, if recurrence occurs. Be currently participating (or participated within the previous 6 months) in an investigational therapeutic or device trial. Exhibiting signs of moderate or severe chronic respiratory disease (such as COPD, asthma, or pulmonary fibrosis). Patient with rheumatologic disorders. History of chronic liver disease or patient showing signs of clinical jaundice at the time of screening. History of severe chronic kidney disease or requiring dialysis. Patient with NYHA Class III or IV congestive heart failure or life-threatening arrhythmias. Subjects with a history of bleeding disorders, anticoagulation therapy that cannot be stopped as prior to the treatment. Any unstable condition of clinical significance, e.g., uncontrolled hypertension, unstable angina pectoris, worsening asthma. Hydroxychloroquine, oral or parenteral corticosteroids, immunosuppressants, or immunomodulating agents within 21 days prior to the Day 0/treatment visit. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood pregnancy test at screening which will be within 72 hours of the IP infusion. Subject has a body mass index (BMI) greater than 42 kg/m2 Subject has or had an active infection requiring systemic antibiotics within 12 weeks of enrollment in the study Inability to perform any of the assessments required for endpoint analysis. Active listing (or expected future listing) for transplant of any organ. Be a solid organ transplant recipient. This does not include prior cell-based therapy (>12 months prior to enrollment), bone, skin, ligament, tendon or corneal grafting. Have a history of organ or cell transplant rejection. History of drug abuse (illegal "street" drugs except marijuana, if it is legal to use in states where patient resides), or prescription medications not being used appropriately for a pre-existing medical condition or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months Patients with untreated HIV infection. However, patients can be enrolled if have been treated for HIV and the test negative for HIV viral load but still test positive for antibodies.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Alocyte Low dose

    Alocyte Medium dose

    Alocyte High dose

    Arm Description

    Subjects will receive low dose injection in a single facet joint

    Subjects will receive medium dose injections in three facet joints

    Subjects will receive high dose injections in five facet joints

    Outcomes

    Primary Outcome Measures

    Safety of Alocyte treatment adverse events
    To evaluate safety ( incident of grade 3 or 4 or treatment emergent serious adverse events) of Alocyte administered in subjects experiencing Facetogenic back pain at a low, medium and high dose.
    Incidence of treatment emergent adverse events as assessed by complete blood count safety lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete blood count (CBC with differential)
    Incidence of treatment emergent adverse events as assessed by complete blood count safety lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete blood count (CBC with differential)
    Incidence of treatment emergent adverse events as assessed by complete blood count safety lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete blood count (CBC with differential)
    Incidence of treatment emergent adverse events as assessed by safety complete metabolic panel ab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete metabolic panel (CMP)
    Incidence of treatment emergent adverse events as assessed by safety complete metabolic panel lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete metabolic panel (CMP)
    Incidence of treatment emergent adverse events as assessed by safety complete metabolic panel lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete metabolic panel (CMP)
    Incidence of treatment emergent adverse events as assessed by safety coagulation panel lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test coagulation panel
    Incidence of treatment emergent adverse events as assessed by safety coagulation panel lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test coagulation panel
    Incidence of treatment emergent adverse events as assessed by safety coagulation panel lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test coagulation panel
    Incidence of treatment emergent adverse events as assessed by blood biomarker sample lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by blood biomarker sample test C-reactive protein (CRP)
    Incidence of treatment emergent adverse events as assessed by blood biomarker sample lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by blood biomarker sample test C-reactive protein (CRP)
    Incidence of treatment emergent adverse events as assessed by blood biomarker sample lab tests
    To evaluate the incidence of treatment emergent adverse events as assessed by blood biomarker sample test C-reactive protein (CRP)

    Secondary Outcome Measures

    Efficacy of Alocyte treatment as assessed by the change in Quality of Life (QoL) SF-12 questionnaire
    Change from baseline in subject QoL SF-12 questionnaire consisting of twelve questions that measure eight health domains to assess physical and mental health. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning
    Efficacy of Alocyte Treatment for pain management as assessed by the change in Numeric Rating Scale (NRS) pain scale
    Change between baseline in pain using the Numeric Rating Scale (NRS) on a scale from 0 (equals no pain) to 10 (worst pain imaginable)
    Efficacy of Alocyte Treatment for pain as assessed by the change in the Owestry Back Pain questionnaire
    Change between baseline in back pain using Oswestry Low back pain questionnaire made up of 10 questions. Each question is scored from 0-5 (minimum to maximum).

    Full Information

    First Posted
    May 25, 2023
    Last Updated
    August 28, 2023
    Sponsor
    Alimorad Farshchian
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05909709
    Brief Title
    Dose Escalation Pilot Study to Evaluate the Safety of Alocyte for the Treatment of Facetogenic Back Pain
    Official Title
    An Open Label Dose Escalation Pilot Study to Evaluate the Safety of Alocyte Delivered Via Intra-articular Facet Injection for the Treatment of Facetogenic Back Pain
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 15, 2023 (Anticipated)
    Primary Completion Date
    October 1, 2025 (Anticipated)
    Study Completion Date
    October 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Alimorad Farshchian

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to see if the use of Alocyte (cord blood plasma plus mononucleic cells) will be safe, well tolerated, and whether it causes any side effects. The study will also examine if the use of the Investigational Product (IP) is able to reduce local inflammation or alleviate Facetogenic back pain
    Detailed Description
    Ghormley, in 1933, was the first to perform oblique spine radiographs to view the zygapophysial or facet joints and coin the term "facet syndrome" to refer to LBP with "sciatica" originating from the facet joints. The facet joint may be affected by systemic disease, such as rheumatoid arthritis and ankylosing spondylitis, or be site of micro traumatic fractures, such as osteoarthritis, meniscoid entrapment, synovial impingement, joint subluxation, synovial inflammation, loss of cartilage, and mechanical injury. Facetogenic pain is the result of repetitive stress and/or cumulative low-level trauma, leading to inflammation and stretching of the joint capsule. Current treatment options for this disease are limited to symptomatic treatment, including analgesics, physiotherapy, and minimally invasive or surgical treatment (spinal fusion or non-fusion), but none of the methods addresses the underlying problem. The pathological process of intervertebral disc degeneration cannot be prevented by these therapies. Alocyte is a cellular, minimally manipulated product derived from umbilical cord blood. Alocyte's manufacturing methodology is designed to enrich human umbilical cord plasma and human umbilical cord blood-derived mononuclear cells (hematopoietic lineage cells such as lymphocytes, monocytes, stem and progenitor cells, as well as mesenchymal stem cells) present in full-term cord blood. The final product is composed of a heterogenous population of cellular products, mainly the exosomes, cytokines, and nucleated cells. Cytokine expression of Alocyte was fully evaluated. Alocyte showed a robust expression of RANTES, Osteopontin, and Angiostatin where the first two are stem cell repair cytokines and the latter is pro-angiogenic cytokine. Other cytokine showed moderate levels are IL-8, PDGF-BB, TIMP-1, TIMP-2, Angiopoietin-1, Angiogenin, MMP-9, Tie-2, uPAR, BDNF, TGF-ß2, GRO, IGFBP-1, IGFBP-2, IL-8, IL-12-p40, MIF, and NAP-2. Alocyte contained a variety of pro-angiogenic, immune-modulatory, anti-inflammatory, pro-metabolism, and tissue repair growth factors. Therefore, a regenerative approach for treating Facetogenic pain will be beneficial by promoting changes in the pathogenic mechanism triggered by the cellular therapeutic product Alocyte.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Facet Joints; Degeneration, Back Pain, Facet Joint Pain
    Keywords
    Back pain, Facet joint pain

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    15 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Alocyte Low dose
    Arm Type
    Experimental
    Arm Description
    Subjects will receive low dose injection in a single facet joint
    Arm Title
    Alocyte Medium dose
    Arm Type
    Experimental
    Arm Description
    Subjects will receive medium dose injections in three facet joints
    Arm Title
    Alocyte High dose
    Arm Type
    Experimental
    Arm Description
    Subjects will receive high dose injections in five facet joints
    Intervention Type
    Drug
    Intervention Name(s)
    Alocyte low dose
    Intervention Description
    Low dose containing 0.2 - 1.0 x 10^11 particles and 3-10x10^6 cell in 2mL which will be administered intra-facet into a single facet joint. Preparation of low dose: 1ml of Alocyte will be diluted with 9ml of saline. After mixing well, only 2ml of the diluted product will be used.
    Intervention Type
    Drug
    Intervention Name(s)
    Alocyte medium dose
    Intervention Description
    Medium dose containing 0.6 - 3.0 x 10^11 particles and 9-30x10^6 cell in 6mL which will be administered intra-facet into three facet joints delivering 2ml/facet joint. Preparation of medium dose: 1ml of Alocyte will be diluted with 9ml of saline. After mixing well, only 6ml of the diluted product will be used.
    Intervention Type
    Drug
    Intervention Name(s)
    Alocyte high dose
    Intervention Description
    High dose containing 1.0 - 5.0 x 10^11 particles and 15-50x10^6 cell in 10mL which will be administered intra-facet into five facet joints delivering 2ml/facet joint. Preparation of high dose: 1ml of Alocyte will be diluted with 9ml of saline. After mixing well, 10ml of diluted product will be used.
    Primary Outcome Measure Information:
    Title
    Safety of Alocyte treatment adverse events
    Description
    To evaluate safety ( incident of grade 3 or 4 or treatment emergent serious adverse events) of Alocyte administered in subjects experiencing Facetogenic back pain at a low, medium and high dose.
    Time Frame
    through study completion, an average of 13 months
    Title
    Incidence of treatment emergent adverse events as assessed by complete blood count safety lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete blood count (CBC with differential)
    Time Frame
    at 1 month
    Title
    Incidence of treatment emergent adverse events as assessed by complete blood count safety lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete blood count (CBC with differential)
    Time Frame
    at 3 months
    Title
    Incidence of treatment emergent adverse events as assessed by complete blood count safety lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete blood count (CBC with differential)
    Time Frame
    at 6 months months
    Title
    Incidence of treatment emergent adverse events as assessed by safety complete metabolic panel ab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete metabolic panel (CMP)
    Time Frame
    at 1 month
    Title
    Incidence of treatment emergent adverse events as assessed by safety complete metabolic panel lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete metabolic panel (CMP)
    Time Frame
    at 3 month
    Title
    Incidence of treatment emergent adverse events as assessed by safety complete metabolic panel lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test complete metabolic panel (CMP)
    Time Frame
    at 6 month
    Title
    Incidence of treatment emergent adverse events as assessed by safety coagulation panel lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test coagulation panel
    Time Frame
    at 1 month
    Title
    Incidence of treatment emergent adverse events as assessed by safety coagulation panel lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test coagulation panel
    Time Frame
    at 3 months
    Title
    Incidence of treatment emergent adverse events as assessed by safety coagulation panel lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by safety lab blood sample test coagulation panel
    Time Frame
    at 6 months
    Title
    Incidence of treatment emergent adverse events as assessed by blood biomarker sample lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by blood biomarker sample test C-reactive protein (CRP)
    Time Frame
    at 1 month
    Title
    Incidence of treatment emergent adverse events as assessed by blood biomarker sample lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by blood biomarker sample test C-reactive protein (CRP)
    Time Frame
    at 3 months
    Title
    Incidence of treatment emergent adverse events as assessed by blood biomarker sample lab tests
    Description
    To evaluate the incidence of treatment emergent adverse events as assessed by blood biomarker sample test C-reactive protein (CRP)
    Time Frame
    at 6 months
    Secondary Outcome Measure Information:
    Title
    Efficacy of Alocyte treatment as assessed by the change in Quality of Life (QoL) SF-12 questionnaire
    Description
    Change from baseline in subject QoL SF-12 questionnaire consisting of twelve questions that measure eight health domains to assess physical and mental health. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning
    Time Frame
    baseline, 1 month, 3 months, 6 months, 12 months
    Title
    Efficacy of Alocyte Treatment for pain management as assessed by the change in Numeric Rating Scale (NRS) pain scale
    Description
    Change between baseline in pain using the Numeric Rating Scale (NRS) on a scale from 0 (equals no pain) to 10 (worst pain imaginable)
    Time Frame
    baseline, 1 month, 3 months, 6 months, 12 months
    Title
    Efficacy of Alocyte Treatment for pain as assessed by the change in the Owestry Back Pain questionnaire
    Description
    Change between baseline in back pain using Oswestry Low back pain questionnaire made up of 10 questions. Each question is scored from 0-5 (minimum to maximum).
    Time Frame
    baseline, 1 month, 3 months, 6 months, 12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: In order to be eligible to participate in this study, all individuals must meet all of the following criteria: Subjects age > 18 years at the time of signing the Informed Consent Form. Male or Female. Ability of participant to understand and the willingness to sign a written informed consent document. Facetogenic back pain diagnosed using the following diagnostic criteria Subjects who have chronic low back pain based on clinical evaluation. Pain onset at dorsal extension and release at flexion is often considered suggestive for facet pain, even if non-specific, such as maximal tenderness upon deep palpation of posterior elements. Patient with up to 5 diseased facet joints Chronic Facetogenic pain (≥ 6 months) in patients that have failed conservative management Subjects must be reasonably able to return for multiple follow-up visits. For Women of Child-Bearing Potential (WOCBP) only, willingness to use FDA-recommended birth control until 6 months post treatment. Any male subject must agree to use contraceptives and not donate sperm during the study. Exclusion Criteria: Previous surgical intervention for back pain Previous stem cell injection(s) within the last year Use of anticoagulation or NSAIDs within 5 days of the injection MRI finding of severe high-grade lumbar stenosis Leg pain exceeding back pain Pain worse with flexion maneuvers Fracture of lumbar vertebrae Inability to perform any of the assessments required for endpoint analysis. Clinically significant abnormal screening laboratory or clinical assessment values Use of medications during the early phase of treatment such as chronic narcotic use, systemic corticosteroid administration, local corticosteroid injection at facets anticoagulant therapy and viscosupplementation into facets, any investigational drug used within 3 months prior to screening or during study and surgery in the facets Subjects with serious co-morbidities are excluded. Evidence of inflammatory arthritis (example, rheumatoid arthritis and ankylosing spondylitis) or traumatic fractures, osteoarthritis, meniscoid entrapment, synovial impingement, joint subluxation, synovial inflammation, loss of cartilage, and mechanical injury. Have a clinical history of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), except curatively treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma, if recurrence occurs. Be currently participating (or participated within the previous 6 months) in an investigational therapeutic or device trial. Exhibiting signs of moderate or severe chronic respiratory disease (such as COPD, asthma, or pulmonary fibrosis). Patient with rheumatologic disorders. History of chronic liver disease or patient showing signs of clinical jaundice at the time of screening. History of severe chronic kidney disease or requiring dialysis. Patient with NYHA Class III or IV congestive heart failure or life-threatening arrhythmias. Subjects with a history of bleeding disorders, anticoagulation therapy that cannot be stopped as prior to the treatment. Any unstable condition of clinical significance, e.g., uncontrolled hypertension, unstable angina pectoris, worsening asthma. Hydroxychloroquine, oral or parenteral corticosteroids, immunosuppressants, or immunomodulating agents within 21 days prior to the Day 0/treatment visit. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood pregnancy test at screening which will be within 72 hours of the IP infusion. Subject has a body mass index (BMI) greater than 42 kg/m2 Subject has or had an active infection requiring systemic antibiotics within 12 weeks of enrollment in the study Inability to perform any of the assessments required for endpoint analysis. Active listing (or expected future listing) for transplant of any organ. Be a solid organ transplant recipient. This does not include prior cell-based therapy (>12 months prior to enrollment), bone, skin, ligament, tendon or corneal grafting. Have a history of organ or cell transplant rejection. History of drug abuse (illegal "street" drugs except marijuana, if it is legal to use in states where patient resides), or prescription medications not being used appropriately for a pre-existing medical condition or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months Patients with untreated HIV infection. However, patients can be enrolled if have been treated for HIV and the test negative for HIV viral load but still test positive for antibodies.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Patricia Graham, MS, CCRC
    Phone
    3057889303
    Email
    pgraham@assureimmune.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Alimorad Farshchian, MD
    Phone
    3058914686
    Email
    genorthix@yahoo.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Alimorad Farshchian, MD
    Organizational Affiliation
    The Center For Regenerative Medicine Laboratories
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Dose Escalation Pilot Study to Evaluate the Safety of Alocyte for the Treatment of Facetogenic Back Pain

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