Randomized Double-Blind Phase 2 Efficacy and Safety of Autologous HB-MSCs vs Placebo for Treatment of Multiple Sclerosis

Study Overview
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Brief Summary
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Randomized Double-Blind Efficacy and safety study of Autologous HB-adMSCs versus placebo for the treatment of Multiple Sclerosis. This study will be for 24 subjects with 6 infusions over a 52 week period. Study participants will continue their established concomitant medications during participation in this investigation.

Detailed Description
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Each eligible study subject will receive a total of 6 intravenous infusions of HB-adMSCs or placebo. Study infusions will be administered with the following regimen, Week 0, 4, 8, 16, 24, and 32. There will be one follow-up visit and end of study at week 52.

Official Title
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A Randomized, Double-Blind, Single-Center, Phase 2, Efficacy and Safety Study of Autologous HB-adMSCs vs Placebo for the Treatment of Patients With Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Biological: HB-adMSCs
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants 18 - 75 years of age. Study participants must have been diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) for at least 6 months before study participation. Study participants must be stabilized on any MS therapy for at least 6 months prior to randomization. Study participants must agree not to increase or begin any Diseases Modifying Therapies for MS during participation in the clinical trial. Study participants must have an EDSS score between 3.0 to 6.5. (Patient must be able to walk). Study participants must have previously banked their mesenchymal stem cells with Hope Biosciences. Study participants should be able to read, understand, and provide written consent. Before any clinical-trial-related procedures are performed, informed consent must be obtained from the participants voluntarily. Female study participants should not be pregnant or plan to become pregnant during study participation and for 6 months after last investigational product administration. * Male participants, if their sexual partners can become pregnant, should use a method of contraception during study participation and for 6 months after the last administration of the investigated product. * Study participant is able and willing to comply with the requirements of this clinical trial. Participants in the study should have evidence of disease, as shown by MRIs of the brain or spinal cord, with the most recent being within 1 year of the screening date, and no other signs of relapse. Exclusion Criteria: Pregnancy, lactation. Women of childbearing age who are not pregnant but do not take effective contraceptive measures. * Study participants with other types of multiple sclerosis, such as progressive relapsing, primary or secondary progressive. Study participant has any active malignancy, including but not limited to evidence of cutaneous basal, squamous cell carcinoma, or melanoma. Study participant has known addiction or dependency or has current substance use or abuse. Study participant has 1 or more significant concurrent medical conditions (verified by medical records), including the following: Poorly controlled diabetes mellitus (PCDM) defined as history of deficient standard of care treatment and/or pre-prandial glucose >130mg/dl during screening visit or post-prandial glucose >200mg/dl. Medical History of Chronic kidney disease (CKD) diagnosis and/or screening results of eGFR < 59mL/min/1.73m2. Presence of New York Heart Association (NYHA) Class III/IV heart failure during screening visit. Any medical history of myocardial infarction in any of the different types, such as ST-elevation myocardial infarction (STEMI) or non-ST-elevated myocardial infarction (NSTEMI), coronary spasm, or unstable angina. Medical history of uncontrolled high blood pressure defined as a deficient standard of care treatment and/or blood pressure > 180/120 mm/Hg during screening visit.Medical history of diseases such as, inherited thrombophilias, cancer of the lung, brain, lymphatic, gynecologic system (ovary or uterus), or gastrointestinal tract (like pancreas or stomach). Medical history of conditions, such as recent major general surgery, (within 12 months before the Screening), lower extremity paralysis due to spinal cord injury, fracture of the pelvis, hips, or femur. Study participant has received any stem cell treatment within 12 months before first dose of investigational product other than stem cells produced by Hope Biosciences. The study participant has received any experimental drug within 12 months before the first dose of the investigational product. (Except for COVID-19 vaccinations) Study participant has a laboratory abnormality during screening, including the following: White blood cell count < 3000/mm3 Platelet count < 80,000mm3 Absolute neutrophil count < 1500/mm3 Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 10 upper limit of normal (ULN) x 1.5 Study participant has any other laboratory abnormality or medical condition which, in the opinion of the investigator poses a safety risk or will prevent the subject from completing the study. The study participant has any concurrent neurologic disease, including hereditary conditions that the principal investigator considers could interfere with the study participation. Some of these neurologic diseases could be Charcot-Marie-Tooth (CMT) or Spinocerebellar Ataxia (SCA). Study participant has any ongoing infection, including TB, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HIV, or syphilis infections, as well as hepatitis B surface antigen positive, and or/ hepatitis C PCR positivity. Study participant is unlikely to complete the study or adhere to the study procedures. Study participant has a previously diagnosed psychiatric condition which in the opinion of the investigator may affect self-assessments. Study participants with any systemic infection requiring treatment with antibiotics, antivirals, or antifungals within 30 days prior to first dose of the investigational product. Male study participants who plan to donate sperm during the study or within 6 months after the last dose. Female patients who plan to donate eggs or undergo in vitro fertilization treatment during the study or within 6 months after the last dose. Study participants who are determined by the Investigator to be unsuitable for study enrollment for other reasons. Participants' life expectancy must not have been considerably limited by other comorbidities, a history of previous myelodysplasia, or hematologic illness. Acceptable reversible and permanent methods of birth control include: 1. True sexual abstinence (abstaining from sexual activity during the entire period of risk). 2. Surgery (occlusion bilateral tubal ligation, vasectomized partner). 3. Hormonal contraceptives associated with ovulation inhibition (oral, injectable, implantable patch, or intravaginal). 4. Intrauterine device (IUD), or intrauterine hormone-releasing system (IUS).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-Blind
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Adipose derived Mesenchymal stem cells (Autologous) | Biological: HB-adMSCs<br>* Autologous product<br>* Other names: Hope Biosciences adipose derived mesenchymal stem cells;|
| Placebo Comparator: Placebo<br>Normal Saline | Drug: Placebo<br>* Normal Saline<br>* Other names: 0.9% NS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the efficacy of intravenous infusions of HB-adMSCs vs placebo in patients with Multiple Sclerosis as determined by improvements in the Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument. | The MSQOL-54 is a comprehensive health-related quality of life measure incorporating general and MS-specific questions into a single instrument. The developers used the SF-36 as a base and added 18 questions to address MS-specific problems, including fatigue and cognitive function. This 54-item questionnaire provides 12 sub-scales, two summary scores, and two extra single-item measures. The sub-scales are physical function, role limits-physical, emotional role restrictions, pain, emotional well-being, energy, health perceptions, social position, cognitive function, health distress, overall quality of life, and sexual function. There is no single overall score for MSQOL-54. Two summary scores - physical health and mental health - can be derived from a weighted combination of scale scores (scale scores range from 0 to 100 and a higher scale score indicates improved quality of life). | Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of intravenous infusions of HB-adMSCs vs placebo in patients with Multiple Sclerosis as determined by changes in the Expanded Disability Status Scale (EDSS) | The EDSS is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. This scale ranges from 0 to 10 in 0.5-unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. | Baseline to Week 52 | 
| To evaluate the efficacy of intravenous infusions of HB-adMSCs vs placebo in patients with Multiple Sclerosis as determined by changes in the Barthel Index | The Barthel index is an ordinal scale that evaluates functional independence in the domains of personal care and mobility. A total of ten variables describing activities of daily living and mobility are considered, with a higher number reflecting better capacity to operate independently. The Barthel Index assesses the level of help needed by a person on a set of ten activities of daily living (ADL) related to mobility and self-care. | Baseline to Week 52 | 
| To determine the efficacy of intravenous infusions of HB-adMSCs vs. Placebo in patients with Multiple Sclerosis as determined by changes in 9-Hole Peg Test | The 9-HPT is a short, standardized upper extremity exam. It measures the time taken to complete the test activity, recorded in seconds. The higher the score the worse the disability. | Baseline to Week 52 | 
| To identify the safety of intravenous infusions of HB-adMSCs vs. Placebo in patients with Multiple Sclerosis as determined by changes in Patient Health Questionnaire (PHQ-9) | The PHQ-9 is the most used depression and suicidal thoughts screening test used to monitor the severity of depression and response to treatment. Depression Severity: 0-4 none, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe. | Baseline to Week 52 | 
| To assess the safety of intravenous infusions of HB-adMSCs vs. Placebo in patients with Multiple Sclerosis as determined by the incidence of adverse events or serious adverse events | Incidence and risk of AEs of special interest (serious or non-serious), including thromboembolic events, peripheral events defined as, thromboembolism of the extremities, also infections and hypersensitivities. | Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal Stem Cells, MS, RRMS, stem cells, MSCs, Relapsing, Remitting