Phase 1/2a Clinical Trial to Assess the Safety of HB-adMSCs for the Treatment of Rheumatoid Arthritis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm Single IV administration of autologous adipose-derived mesenchymal stem cells Baseline laboratory data will be collected prior to infusion; follow up data will be compared against baseline at 1, 3, 6 and 12 months. Joint Assessment 68 will be administered at 1, 3, 6 and 12 months. |
Biological: HB-adMSCs
Hope Biosciences autologous adipose-derived mesenchymal stem cells
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Accurate Clinical Research | Pasadena | Texas | United States | 77034 |
Sponsors and Collaborators
- Hope Biosciences
Investigators
- Principal Investigator: Philip Waller, MD, Accurate Clinical Research
Study Documents (Full-Text)
More Information
Publications
None provided.- HBRA01
Study Results
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 Detail | Of 23 screened participants, 15 met inclusion criteria, were enrolled, and given treatment. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs). |
| Period Title: Overall Study | |
| STARTED | 15 |
| Per Protocol Population Day 1 | 15 |
| Per Protocol Population Week 1 | 15 |
| Per Protocol Population Week 4 | 14 |
| Per Protocol Population Week 8 | 13 |
| Per Protocol Population Week 12 | 15 |
| Per Protocol Population Week 26 | 14 |
| Per Protocol Population Week 52 | 13 |
| COMPLETED | 15 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) cells. |
| Overall Participants | 15 |
| Age (years) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [years] |
52
|
| Sex: Female, Male (Count of Participants) | |
| Female |
14
93.3%
|
| Male |
1
6.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
4
26.7%
|
| Not Hispanic or Latino |
11
73.3%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
6.7%
|
| White |
14
93.3%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
15
100%
|
| Baseline Tumor Necrosis Factor alpha (TNF-a) in patients with acute RA (pg/mL) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [pg/mL] |
1.45
|
| Baseline Interleukin-6 (IL-6) in patients with acute RA (pg/mL) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [pg/mL] |
4.90
|
| Baseline C-Reactive Protein (CRP) in patients with acute RA (mg/L) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [mg/L] |
10.0
|
| Baseline Erythrocyte Sedimentation Rate (ESR) in patients with acute RA (mm/hr) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [mm/hr] |
43.0
|
| Baseline joint count in patients with acute RA. (number of joints) [Median (Inter-Quartile Range) ] | |
| Tender |
20.0
|
| Swollen |
12.0
|
Outcome Measures
| Title | Total Number of Adverse Events and Serious Adverse Events |
|---|---|
| Description | Total number of Adverse Events and Serious Adverse Events across all subjects over 12 months. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment and completed at least 5 of 7 follow up assessments. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) cells. |
| Measure Participants | 15 |
| Total Adverse Events |
27
|
| Mild Adverse Events |
15
|
| Moderate Adverse Events |
8
|
| Severe Adverse Events |
4
|
| Treatment Related Mild Adverse Events |
4
|
| Treatment Related Moderate Adverse Events |
0
|
| Treatment Related Severe Adverse Events |
0
|
| Title | The Effect of Single Injection of HB-adMSCs on TNF-a in Patients With Acute RA |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment and completed at least 5 of 7 follow up assessments. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) |
| Measure Participants | 15 |
| Median (Inter-Quartile Range) [pg/mL] |
1.15
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.743 |
| Comments | ||
| Method | Wilcoxon-signed rank test | |
| Comments | Effect Size: 0.09 | |
| Title | The Effect of Single Injection of HB-adMSCs on IL-6 in Patients With Acute RA |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment and completed at least 5 of 7 follow up assessments. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) |
| Measure Participants | 15 |
| Median (Inter-Quartile Range) [pg/mL] |
4.60
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.714 |
| Comments | ||
| Method | Wilcoxon-signed rank test | |
| Comments | Effect Size: 0.10 | |
| Title | The Effect of Single Injection of HB-adMSCs on CRP in Patients With Acute RA |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment and completed at least 5 of 7 follow up assessments. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) |
| Measure Participants | 15 |
| Median (Inter-Quartile Range) [mg/L] |
6.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.183 |
| Comments | ||
| Method | Wilcoxon-signed rank test | |
| Comments | Effect Size: 0.37 | |
| Title | The Effect of Single Injection of HB-adMSCs on ESR in Patients With Acute RA |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment and completed at least 5 of 7 follow up assessments. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) |
| Measure Participants | 15 |
| Median (Inter-Quartile Range) [mm/hr] |
34.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.775 |
| Comments | ||
| Method | Wilcoxon-signed rank test | |
| Comments | Effect Size: 0.05 | |
| Title | The Effect of Single Injection of HB-adMSCs on Joint Count in Patients With Acute RA. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment and completed at least 5 of 7 follow up assessments. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) |
| Measure Participants | 15 |
| Tender |
1.00
|
| Swollen |
1.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm |
|---|---|---|
| Comments | Tender Joint Count | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | ||
| Method | Wilcoxon-signed rank test | |
| Comments | Effect Size: 0.93 | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm |
|---|---|---|
| Comments | Swollen Joint Count | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | ||
| Method | Wilcoxon-signed rank test | |
| Comments | Effect Size: 0.83 | |
Adverse Events
| Time Frame | 12 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Treatment Arm | |
| Arm/Group Description | Single IV administration of Hope Biosciences autologous adipose-derived mesenchymal stem cells (HB-adMSCs) | |
All Cause Mortality |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | |
Serious Adverse Events |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/15 (26.7%) | |
| Gastrointestinal disorders | ||
| Intestinal Obstruction | 1/15 (6.7%) | 1 |
| Abdominal Pain | 1/15 (6.7%) | 1 |
| Renal and urinary disorders | ||
| Urinary Tract Infection | 1/15 (6.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Skin Infection | 1/15 (6.7%) | 3 |
| Surgical and medical procedures | ||
| Intestinal Resection | 1/15 (6.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 14/15 (93.3%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 2/15 (13.3%) | 2 |
| Thrombocytopenia | 1/15 (6.7%) | 1 |
| Eye disorders | ||
| Eye Pruritus | 1/15 (6.7%) | 1 |
| Gastrointestinal disorders | ||
| Intestinal Obstruction | 1/15 (6.7%) | 1 |
| Immune system disorders | ||
| Rheumatoid arthritis | 2/15 (13.3%) | 2 |
| Infections and infestations | ||
| Influenza | 1/15 (6.7%) | 1 |
| Tooth Infection | 1/15 (6.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Muscle Spasms | 1/15 (6.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Cyst | 1/15 (6.7%) | 1 |
| Renal and urinary disorders | ||
| Renal Failure | 2/15 (13.3%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 1/15 (6.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Skin Infection | 1/15 (6.7%) | 1 |
| Rash | 1/15 (6.7%) | 2 |
| Surgical and medical procedures | ||
| Tooth Extraction | 1/15 (6.7%) | 1 |
| Vascular disorders | ||
| Hematuria | 2/15 (13.3%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In the protocol signature page, the investigator agreed to the following: "I further agree to treat the results of this Study as confidential information and will not submit the results of the Study for publication without prior written authorization from Hope Biosciences. "
Results Point of Contact
| Name/Title | Linette Rehkopf RPh |
|---|---|
| Organization | Hope Biosciences Stem Cell Research Foundation |
| Phone | 346-900-0340 ext 102 |
| linette@hopebio.org |
- HBRA01