"HB-adMSCs for the Treatment of Patients With Multiple Sclerosis"

"A Phase 2, Open Label, Efficacy and Safety Study of Autologous HB-adMSCs for the Treatment of Patients With Multiple Sclerosis"

This protocol is part of a clinical study to evaluate efficacy and safety of multiple intravenous administrations of HB-adMSCs for the treatment of Multiple Sclerosis.

This clinical trial is designed as an open label, single center, phase 2 study to assess the efficacy and safety of multiple autologous adipose derived mesenchymal stem cells in patients with Relapsing Remitting Multiple Sclerosis. The trial includes a screening period of up to 4 weeks, a 32-week treatment period, and a safety Follow-up period of 20 weeks after the last investigational product administration. This clinical trial will be opened to enroll up to 10 eligible subjects diagnosed with Relapsing Remitting Multiple Sclerosis. Each eligible study subject will receive a total of 6 intravenous infusions of HB-adMSCs. Study infusions will be administered with the following regimen, Week 0, 4, 8, 16, 24 and 32, this dosing interval has been selected because due to the efficacy observed in the completed placebo-controlled counterpart to this study, HBMS01 (IND 027633, NCT05116540). Efficacy was observed at the end of study visit (week 52), post-therapy with six infusions of HB-adMSCs. The following objectives will be investigated: efficacy as determined by the Multiple Sclerosis Quality of Life (MSQOL-54) Instrument, efficacy as determined by changes in Expanded Disability Status Scale (EDSS), safety as determined by changes in Patient Health Questionnaire (PHQ-9), and safety as determined by the incidence of adverse events or serious adverse events.

Inclusion Criteria:

1. Male and female subjects 18 - 75 years of age.

2. Study subjects must have been diagnosed with Relapsing Remitting Multiple Sclerosis (RRMS) for at least 6 months before study participation.

3. Study subjects must have been randomized into the placebo group and completed participation in the HBMS01 clinical trial (IND 027633). (A randomized, double-blind, single center, phase 2 clinical trial that assessed the efficacy and safety of autologous HB-adMSCs vs placebo for the treatment of patients with Multiple Sclerosis.)

4. Study subjects must be stabilized on any MS therapy for at least 6 months prior to enrollment.

5. Study subjects must agree not to increase or begin any Diseases Modifying Therapies for MS during participation in the clinical trial.

6. Study subjects must have an EDSS score between 3.0 to 6.5. (Patient must be able to walk).

7. Study subjects must have previously banked their mesenchymal stem cells with Hope Biosciences.

8. Study subjects should be able to read, understand and to provide written consent.

9. Before any clinical-trial-related procedures are performed, informed consent must be obtained from the subjects voluntarily.

10. Female study subjects of childbearing potential should not be pregnant or plan to become pregnant during study participation and for 6 months after the last investigational product administration. Female study subjects of childbearing potential should confirm the use of one of the following contraceptive measures:

    • Hormonal contraceptives associated with ovulation inhibition (oral, injectable, implantable, patch, or intravaginal).
    • Intrauterine device (IUD), or intrauterine hormone-releasing system (IUS).
    • Barrier contraceptive methods (condoms, diaphragm, etc.).
    • Surgery (occlusion bilateral tubal ligation, hysterectomy, vasectomized partner).

11. Male subjects if their sexual partners can become pregnant should ensure the use one of the following methods of contraception during study participation and for 6 months after the last administration of the investigated product:

    • Hormonal contraceptives associated with ovulation inhibition (oral, injectable, implantable, patch, or intravaginal).
    • Intrauterine device (IUD), or intrauterine hormone-releasing system (IUS).
    • Barrier contraceptive methods (condoms, diaphragm, etc.).
    • Surgery (vasectomy, occlusion bilateral tubal ligation (partner), hysterectomy (partner)).

12. Study subject is able and willing to comply with the requirements of this clinical trial.

13. Subjects 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.

Exclusion Criteria:

1. Women who are currently pregnant or lactating.

2. Study subject has any active malignancy, including but not limited to evidence of cutaneous basal, squamous cell carcinoma, or melanoma.

3. Study subject has known addiction or dependency or has current substance use or abuse.

4. Study subject 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.

5. Study subject has received any stem cell treatment within 12 months before first dose of investigational product other than stem cells produced by Hope Biosciences.

6. The study subject has received any experimental drug within 12 months before the first dose of the investigational product. (Except for COVID-19 vaccinations)

7. Study subject 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

8. Study subject 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.

9. The study subject 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).

10. Study subject is unlikely to complete the study or adhere to the study procedures.

11. Study subject has a previously diagnosed psychiatric condition which in the opinion of the investigator may affect self-assessments.

12. Study subject with any systemic infection requiring treatment with antibiotics, antivirals, or antifungals within 30 days prior to first dose of the investigational product.

13. Male study subjects 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.

14. Study subjects who are determined by the Investigator to be unsuitable for study enrollment for other reasons.

15. Subjects' life expectancy must not have been considerably limited by other comorbidities, a history of previous myelodysplasia, or hematologic illness.