Clinical trial NCT05116540: Randomized Double-Blind Phase 2 Efficacy and Safety of Autologous HB-MSCs vs Placebo for Treatment of Multiple Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Mesenchymal Stem Cells
MS
RRMS
stem cells
MSCs
Relapsing
Remitting
Lead sponsor: Hope Biosciences
Sponsor class: INDUSTRY
First posted: 2021-11-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male and female participants 18 - 75 years of age.
2. Study participants must have been diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) for at least 6 months before study participation.
3. Study participants must be stabilized on any MS therapy for at least 6 months prior to randomization.
4. Study participants must agree not to increase or begin any Diseases Modifying Therapies for MS during participation in the clinical trial.
5. Study participants must have an EDSS score between 3.0 to 6.5. (Patient must be able to walk).
6. Study participants must have previously banked their mesenchymal stem cells with Hope Biosciences.
7. Study participants should be able to read, understand, and provide written consent.
8. Before any clinical-trial-related procedures are performed, informed consent must be obtained from the participants voluntarily.
9. Female study participants should not be pregnant or plan to become pregnant during study participation and for 6 months after last investigational product administration. \*
10. 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. \*
11. Study participant is able and willing to comply with the requirements of this clinical trial.
12. 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:

1. Pregnancy, lactation. Women of childbearing age who are not pregnant but do not take effective contraceptive measures. \*
2. Study participants with other types of multiple sclerosis, such as progressive relapsing, primary or secondary progressive.
3. Study participant has any active malignancy, including but not limited to evidence of cutaneous basal, squamous cell carcinoma, or melanoma.
4. Study participant has known addiction or dependency or has current substance use or abuse.
5. 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.
6. 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.
7. The study participant has received any experimental drug within 12 months before the first dose of the investigational product. (Except for COVID-19 vaccinations)
8. 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
9. 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.
10. 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).
11. 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.
12. Study participant is unlikely to complete the study or adhere to the study procedures.
13. Study participant has a previously diagnosed psychiatric condition which in the opinion of the investigator may affect self-assessments.
14. Study participants with any systemic infection requiring treatment with antibiotics, antivirals, or antifungals within 30 days prior to first dose of the investigational product.
15. 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.
16. Study participants who are determined by the Investigator to be unsuitable for study enrollment for other reasons.
17. 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).

Primary outcomes:
measure: Change From Baseline in Physical Health Composite Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument
timeFrame: Baseline to Week 52
measure: Change From Baseline in Mental Health Composite Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Cognitive Function Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Emotional Well-Being Composite Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Health Distress Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in RL/Emotional Problems Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Overall Quality of Life Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Energy/Fatigue Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Health Perception Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Physical Function Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in RL/Physical Problems Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Pain Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Social Function Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Change From Baseline in Sexual Function Score - Multiple Sclerosis Quality of Life (MSQOL) 54 Instrument.
timeFrame: Baseline to Week 52
measure: Analysis of Covariance (ANCOVA) Model - Physical Health Composite Score Change From Baseline Multiple Sclerosis Quality of Life (MSQOL)-54
timeFrame: Baseline to Week 52
measure: Analysis of Covariance (ANCOVA) Model - Mental Health Composite Score Change From Baseline Multiple Sclerosis Quality of Life (MSQOL)-54 Composite Score
timeFrame: Baseline to Week 52
measure: Bayesian Statistical Analysis - Analysis of Covariance (ANCOVA) Model - Physical Health Composite Score Change From Baseline Multiple Sclerosis Quality of Life (MSQOL)-54
timeFrame: Baseline to Week 52
measure: Bayesian Statistical Analysis - Analysis of Covariance (ANCOVA) Model - Mental Health Composite Score Change From Baseline - Multiple Sclerosis Quality of Life (MSQOL)-54
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Analysis of Covariance (ANCOVA) Model - Total Expanded Disability Status Scale (EDSS) Scores Through Week 52 - Change From Baseline - Efficacy Analysis Set
timeFrame: Baseline to Week 52
measure: Analysis of Covariance (ANCOVA) Model - Change From Baseline Barthel Index Scores Through Week 52 - Efficacy Analysis Set
timeFrame: Baseline to Week 52
measure: ANCOVA Model - Change From Baseline 9-Hole Peg Test Scores - Dominant Hand Avg Time Through Week 52
timeFrame: Baseline to Week 52
measure: Analysis of Covariance (ANCOVA) Model - Change From Baseline 9-Hole Peg Test Scores - Non-Dominant Hand Avg Time Through Week 52
timeFrame: Baseline to Week 52
measure: Analysis of Covariance (ANCOVA) Model - Change in Patient Health Questionnaire (PHQ-9) Test Scores
timeFrame: Baseline to Week 52
measure: Baseline Vitals Values - Height
timeFrame: Baseline
measure: Change From Baseline Vitals Values - Weight
timeFrame: Baseline to Week 52
measure: Change From Baseline Vitals Values - Body Mass Index
timeFrame: Baseline to Week 52
measure: Change From Baseline Vitals Values - Respiratory Rate
timeFrame: Baseline to Week 52
measure: Change From Baseline Vitals Values - Temperature
timeFrame: Baseline to Week 52
measure: Change From Baseline Vitals Values - Systolic Blood Pressure
timeFrame: Baseline to Week 52
measure: Change From Baseline Vitals Values - Diastolic Blood Pressure
timeFrame: Baseline to Week 52
measure: Change From Baseline Vitals Values - Pulse Rate
timeFrame: Baseline to Week 52
measure: Change From Baseline Vitals Values - Oxygen Saturation
timeFrame: Baseline to Week 52
measure: Change From Baseline Physical Examination Results - Abdomen
timeFrame: Baseline to Week 52
measure: Change From Baseline Physical Examination Results - Cardiovascular
timeFrame: Baseline to Week 52
measure: Change From Baseline Physical Examination Results - HEENT
timeFrame: Baseline to Week 52
measure: Change From Baseline Physical Examination Results - Lymph Node
timeFrame: Baseline to Week 52
measure: Change From Baseline Physical Examination Results - Musculoskeletal
timeFrame: Baseline to Week 52
measure: Change From Baseline Physical Examination Results - Neurological
timeFrame: Baseline to Week 52
measure: Change From Baseline Physical Examination Results - Respiratory
timeFrame: Baseline to Week 52
measure: Change From Baseline Physical Examination Results - Skin
timeFrame: Baseline to Week 52
measure: Laboratory Values - CBC (x10^3 Cells/uL)
timeFrame: Baseline to Week 52
measure: Laboratory Values - CBC (% of WBC)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CBC (% of Total Blood Cell Count)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CBC (g/dL)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CBC (pg)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CBC (fL)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CBC (x10^6 Cells/uL)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CBC (RDW)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CMP (g/dL)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CMP (Ratio: Albumin (g/dL) to Calc. Globulin (g/dL))
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CMP (U/L)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CMP (mg/dL)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CMP (mEq/L)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CMP (mL/Min/1.73m^2)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - CMP (Ratio: Urea Nitrogen (mg/dL) to Creatinine (mg/dL))
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values - Coagulation Panel (Seconds)
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
measure: Laboratory Values. Coagulation Panel (Ratio: Prothrombin Time (Seconds) / Mean Normal Prothrombin Time (Seconds))
timeFrame: Baseline (Week 0), Week 24, and End of Study (Week 52)
Other outcomes:
Locations:
city: Sugar Land
country: United States
facility: Hope Biosciences Stem Cell Research Foundation
state: Texas
Study officials:
affiliation: Hope Biosciences Stem Cell Research Foundation
name: Djamchid Lotfi, MD
role: PRINCIPAL_INVESTIGATOR
References: