HB-adMSCs vs Placebo for the Treatment of Juvenile Idiopathic Arthritis

A Randomized, Double-Blind, Phase 2, Efficacy and Safety Cross-Over Study of Allogeneic HB-adMSCs vs Placebo for the Treatment of Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis

Methodology: Randomized, double-blind, AB/BA cross-over study with a washout period of 12 weeks.

Treatment Duration: 8 weeks per group

General Objectives: To assess the efficacy and safety of multiple intravenous infusions of allogeneic HB-adMSCs by improving signs and symptoms of juvenile idiopathic arthritis in this subject population.

Number of Subjects: 66 (6 subjects in Cohort 1 and 60 subjects in Cohort 2)

Indication: Juvenile Idiopathic Arthritis

Primary Objectives:

• To assess the safety of intravenous infusions of allogeneic HB-adMSCs vs placebo in patients with oligoarticular or polyarticular juvenile idiopathic arthritis as determined by the incidence of adverse events or serious adverse events. (Time Frame: Week 0 to Week 72).
• To investigate the efficacy of intravenous infusions of allogeneic HB-adMSCs vs placebo in patients with oligoarticular or polyarticular juvenile idiopathic arthritis as determined by improvements in ACR Pedi 30 scores. (Time Frame: Week 0 to Week 52 for Group AB and Week 0 to Week 72 for Group BA).

Secondary Objectives

• To evaluate the efficacy of intravenous infusions of allogeneic HB-adMSCs vs placebo in patients with oligoarticular or polyarticular juvenile idiopathic arthritis as determined by improvements in ACR Pedi 50 scores. (Time Frame: Week 0 to Week 52 for Group AB and Week 0 to Week 72 for Group BA).
• To evaluate the efficacy of intravenous infusions of allogeneic HB-adMSCs vs placebo in patients with oligoarticular or polyarticular juvenile idiopathic arthritis as determined by improvements in ACR Pedi 70 scores. (Time Frame: Week 0 to Week 52 for Group AB and Week 0 to Week 72 for Group BA).
• To evaluate the efficacy of intravenous infusions of allogeneic HB-adMSCs vs placebo in patients with oligoarticular or polyarticular juvenile idiopathic arthritis as determined by improvements in CRP values. (Time Frame: Week 0 to Week 52 for Group AB and Week 0 to Week 72 for Group BA).
• To evaluate the efficacy of intravenous infusions of allogeneic HB-adMSCs vs placebo in patients with oligoarticular or polyarticular juvenile idiopathic arthritis as determined by improvements in ESR values. (Time Frame: Week 0 to Week 52 for Group AB and Week 0 to Week 72 for Group BA).
• To evaluate the efficacy of intravenous infusions of allogeneic HB-adMSCs vs placebo in patients with oligoarticular or polyarticular juvenile idiopathic arthritis as determined by improvements in Peds QL scores. (Time Frame: Week 0 to Week 52 for Group AB and Week 0 to Week 72 for Group BA).

Inclusion Criteria:

The subject will be eligible for inclusion in this clinical trial only if all of the following criteria apply:

1. Male and female subjects who are ≥ 2 years old and < 17 years old.

   a.The first 6 subjects enrolled must be ≥ 12 years old and < 17 years old

2. Must be diagnosed with Oligoarticular or Polyarticular Juvenile Idiopathic Arthritis by a Pediatric Rheumatologist.

3. Must have rheumatoid factor (RF) factor test result documented in medical records.

4. Must have at least 3 affected joints at the screening visit.

5. Must have a body weight of > 10 kg at the screening visit.

6. Subjects without a current established treatment for JIA who are not on treatment because they have failed at least 2 approved medications for their condition, or if being treated, subjects who are on a stable dose of arthritis therapy regimen for ≥3 months prior to screening.

7. Must have an abnormal CRP result and/or abnormal ESR result at screening. Abnormal C-reactive protein (CRP) value defined as > 1 mg/dL. Abnormal Erythrocyte Sedimentation Rate (ESR) value defined as >15 mm/hr for males and >20 mm/hr for females.

8. 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 must confirm usage 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.).

9. 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.).

10. Study subject's parent(s)/LAR is/are able and willing to comply with the requirements of this clinical trial.

11. Voluntarily signed informed consent from study subjects' parent(s) or legally authorized representative obtained before any clinical-trial related procedures are performed.

Exclusion Criteria:

The subject will not be eligible for inclusion in this clinical trial if any of the following criteria apply:

1. Study subject has any of the following laboratory results at the screening visit:

   1. WBC: <3000 cells/μL OR >15000 cells/μL (<3 K cells/μL or >15 K cells/μL)
   2. Hemoglobin: <8 g/dL
   3. Absolute Neutrophil Count: <1500 cells/μL
   4. Platelet: <150000 cells/μL (<150 K cells/μL)
   5. Sodium: <120 mEq/L OR >150 mEq/L
   6. Glucose: >150 mg/dL
   7. Potassium: <3.5 mEq/L OR >6 mEq/L
   8. BUN: >25 mg/dL
   9. Creatinine: >2 mg/dL
   10. BUN/Creatinine ratio: >50
   11. AST: >100 U/L
   12. ALT: >100 U/L

2. Study participant has any vital sign abnormalities at the screening visit as determined by the investigator.

3. Study subject has 1 or more significant uncontrolled concurrent medical conditions (verified by medical records), including the following:

   1. Diabetes Mellitus
   2. Crohn's Disease
   3. Lupus
   4. Multiple Sclerosis

4. Study subject has any active malignancy, including evidence of cutaneous basal, squamous cell carcinoma or melanoma.

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

6. Study subject has received any stem cell treatment within 1 year before first dose of investigational product other than stem cells produced by Hope Biosciences LLC.

7. Receiving any investigational therapy or any approved therapy for investigational use within 1 year prior first dose of the investigational product other than COVID-19 vaccines.

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. Study subject's parent(s)/LAR unable to understand and provide signed informed consent.

10. Study subject and/or study subject's parent(s)/LAR unlikely to complete the study or adhere to the study procedures.

11. Study subject with known concurrent acute or chronic viral hepatis B or C or human immunodeficiency virus (HIV) infection.

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.