Rheumatoid Arthritis
Conditions
Keywords
arthritis, stem cells, MSCs, adipose MSCs
Brief summary
Hope Biosciences is conducting a research study of an investigational product called Hope Biosciences autologous adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as a possible treatment for Rheumatoid Arthritis (RA). The study purpose is to evaluate the safety profile of a single IV infusion of HB-adMSCs in subjects with clinical diagnosis of RA.
Detailed description
This is a Phase 1/2a, open-label, single-dose study in subjects with active Rheumatoid Arthritis (RA). 12-15 patients will be enrolled for the study. The overall objective of this study is to evaluate the safety profile of a single IV infusion of autologous adipose-derived mesenchymal stem cells (HB-adMSCs) in subjects with clinical diagnosis of RA. The primary endpoint of this study is to measure the number and frequency of adverse event(s) and/or severe adverse event(s) throughout the study duration. The second endpoint of this study is to evaluate the ability of HB-adMSCs to alter RA-related inflammation via measuring levels of Tumor Necrosis Factor alpha (TNF-a), Interleukin-6 (IL-6), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and Joint Count 66/68 after a single infusion of autologous HB-adMSCs for up to 12-month post-infusion.
Interventions
BIOLOGICALHB-adMSCs
Hope Biosciences autologous adipose-derived mesenchymal stem cells
Sponsors
Hope Biosciences LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A single IV infusion of autologous adipose-derived mesenchymal stem cells (HB-adMSCs) in subjects with clinical diagnosis of RA.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adult male or female between the ages of 18 and 65 * Patients have active RA as confirmed by the following criteria: * ≥ 6 swollen joints and ≥ 6 tender joints at screening (68-joint count) * Abnormal CRP result OR abnormal ESR result at screening. Abnormal CRP result at screening OR abnormal ESR defined as: * CRP \> 4.9 mg/L or ESR \> 10mm/hr for men, \> 20mm/hr for women * Patients without current established treatment, or if being treated, patients who are on a stable dose of RA therapy regimen for ≥ 4 weeks prior to screening
Exclusion criteria
* Inability to understand and provide signed informed consent * Pregnancy, lactation, or, if female of childbearing potential, positive serum β-hCG at screening. * Currently diagnosed any malignant neoplasm. Any patient who was successfully treated for cancer and has been disease-free, with no recurrence, for at least 5 years, will be considered. * Uncontrolled systemic illness, including, but not limited to: hypertension (systolic \>150 mm Hg or diastolic \>95 mm Hg); diabetes; renal, hepatic, or cardiac failure or any laboratory abnormality that poses a safety risk to the subject such as: * Hemoglobin ≤8.5 g/dL * White blood cells (WBCs) ≤3,500/mm3 (3.5 G/L) * Any other illness which, in the opinion of the investigator, characterizes the subject as not being a good candidate for the study * Participation in another study with an investigational drug or device within 4 weeks prior to treatment or 5 half-lives of the investigational product used (whichever is longer). * Positive results of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), hepatitis C antibody (HCV Ab), and/or human immunodeficiency virus antibody (HIV Ab) tests at screening (excluding patients who are tested positive for HBsAb alone due to a hepatitis B vaccination). * Positive history of Treponema pallidum.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Adverse Events and Serious Adverse Events | 12 months | Total number of Adverse Events and Serious Adverse Events across all subjects over 12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of Single Injection of HB-adMSCs on TNF-a in Patients With Acute RA | 12 months | Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of Tumor Necrosis factor (TNF-a) (pg/mL) measured during trial. |
| The Effect of Single Injection of HB-adMSCs on IL-6 in Patients With Acute RA | 12 months | Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of interleukin 6 (IL-6) (pg/mL) during the trial |
| The Effect of Single Injection of HB-adMSCs on CRP in Patients With Acute RA | 12 months | Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of C-reactive protein (CRP) (mg/L) during the trial |
| The Effect of Single Injection of HB-adMSCs on ESR in Patients With Acute RA | 12 months | Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of erythrosedimentation rate (ESR) (mm/hr) during the trial. |
| The Effect of Single Injection of HB-adMSCs on Joint Count in Patients With Acute RA. | 12 months | Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of Joint Count 66/68 (# joints - tender and swollen) during the trial. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on physician referral and 6 participants were recruited through clinicaltrials.gov. First participant was enrolled on 09/25/2018 and last participant was enrolled on 05/23/2019.
Pre-assignment details
Of 23 screened participants, 15 met inclusion criteria, were enrolled, and given treatment.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) cells. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Treatment Arm |
|---|---|
| Age, Continuous | 52 years |
| Baseline C-Reactive Protein (CRP) in patients with acute RA | 10.0 mg/L |
| Baseline Erythrocyte Sedimentation Rate (ESR) in patients with acute RA | 43.0 mm/hr |
| Baseline Interleukin-6 (IL-6) in patients with acute RA | 4.90 pg/mL |
| Baseline joint count in patients with acute RA. Swollen | 12.0 number of joints |
| Baseline joint count in patients with acute RA. Tender | 20.0 number of joints |
| Baseline Tumor Necrosis Factor alpha (TNF-a) in patients with acute RA | 1.45 pg/mL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 4 / 15 |
Outcome results
Primary
Total Number of Adverse Events and Serious Adverse Events
Total number of Adverse Events and Serious Adverse Events across all subjects over 12 months.
Time frame: 12 months
Population: All participants who received treatment and completed at least 5 of 7 follow up assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Arm | Total Number of Adverse Events and Serious Adverse Events | Total Adverse Events | 27 count of events |
| Treatment Arm | Total Number of Adverse Events and Serious Adverse Events | Mild Adverse Events | 15 count of events |
| Treatment Arm | Total Number of Adverse Events and Serious Adverse Events | Moderate Adverse Events | 8 count of events |
| Treatment Arm | Total Number of Adverse Events and Serious Adverse Events | Severe Adverse Events | 4 count of events |
| Treatment Arm | Total Number of Adverse Events and Serious Adverse Events | Treatment Related Mild Adverse Events | 4 count of events |
| Treatment Arm | Total Number of Adverse Events and Serious Adverse Events | Treatment Related Moderate Adverse Events | 0 count of events |
| Treatment Arm | Total Number of Adverse Events and Serious Adverse Events | Treatment Related Severe Adverse Events | 0 count of events |
Secondary
The Effect of Single Injection of HB-adMSCs on CRP in Patients With Acute RA
Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of C-reactive protein (CRP) (mg/L) during the trial
Time frame: 12 months
Population: All participants who received treatment and completed at least 5 of 7 follow up assessments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | The Effect of Single Injection of HB-adMSCs on CRP in Patients With Acute RA | 6.00 mg/L |
p-value: 0.183Wilcoxon-signed rank test
Secondary
The Effect of Single Injection of HB-adMSCs on ESR in Patients With Acute RA
Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of erythrosedimentation rate (ESR) (mm/hr) during the trial.
Time frame: 12 months
Population: All participants who received treatment and completed at least 5 of 7 follow up assessments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | The Effect of Single Injection of HB-adMSCs on ESR in Patients With Acute RA | 34.5 mm/hr |
p-value: 0.775Wilcoxon-signed rank test
Secondary
The Effect of Single Injection of HB-adMSCs on IL-6 in Patients With Acute RA
Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of interleukin 6 (IL-6) (pg/mL) during the trial
Time frame: 12 months
Population: All participants who received treatment and completed at least 5 of 7 follow up assessments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | The Effect of Single Injection of HB-adMSCs on IL-6 in Patients With Acute RA | 4.60 pg/mL |
p-value: 0.714Wilcoxon-signed rank test
Secondary
The Effect of Single Injection of HB-adMSCs on Joint Count in Patients With Acute RA.
Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of Joint Count 66/68 (# joints - tender and swollen) during the trial.
Time frame: 12 months
Population: All participants who received treatment and completed at least 5 of 7 follow up assessments.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment Arm | The Effect of Single Injection of HB-adMSCs on Joint Count in Patients With Acute RA. | Tender | 1.00 number of joints |
| Treatment Arm | The Effect of Single Injection of HB-adMSCs on Joint Count in Patients With Acute RA. | Swollen | 1.00 number of joints |
Comparison: Tender Joint Countp-value: 0.0008Wilcoxon-signed rank test
Comparison: Swollen Joint Countp-value: 0.003Wilcoxon-signed rank test
Secondary
The Effect of Single Injection of HB-adMSCs on TNF-a in Patients With Acute RA
Efficacy is a secondary endpoint for this study and will be assessed by comparing the levels of Tumor Necrosis factor (TNF-a) (pg/mL) measured during trial.
Time frame: 12 months
Population: All participants who received treatment and completed at least 5 of 7 follow up assessments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | The Effect of Single Injection of HB-adMSCs on TNF-a in Patients With Acute RA | 1.15 pg/mL |
p-value: 0.743Wilcoxon-signed rank test