Allogeneic Human Mesenchymal Stem Cell Injection in PAtieNts With FaceTogenic Back Pain (VALIANT)

A Phase I/II, Randomized, Blinded and Placebo-controlled Trial to EValuate the Safety and Potential Efficacy of Allogeneic Human Mesenchymal Stem Cell Injection in PAtieNts With FaceTogenic Back Pain

The study is a phase I/II trial where allogeneic human mesenchymal stem cells (hMSCs) are injected intracfect into the lumbar facet joints. Forty (40) subjects are scheduled to undergo injection after meeting all inclusion/exclusion criteria will be evaluate at baseline.

Study Overview

• Status: Withdrawn
• Conditions: Back Pain; Facetogenic Back Pain
• Intervention / Treatment: Drug: Placebo; Biological: Allogeneic Human Mesenchymal Stem Cells (hMSCs)

Detailed Description

There are 40 subjects that will be randomized into the trial into one of 4 groups. In the pilot phase 5 subjects will be enrolled into Group 1, and another 5 subjects will be enrolled into Group 2. Subjects in group 1 will receive placebo but will be eligible for a cross over phase where they will receive a injection of the study investigational product.

In the pilot phase, the first three (3) subjects in each treatment group will not be treated less than 10 days apart.

Following the pilot study, thirty (30) subjects will be scheduled to undergo CT guided facet injection of the lumbar facet joints using a posterior approach after meeting all inclusion/exclusion criteria and baseline evaluation.

Eligible participants will be randomized to either Group A or Group B.Group A will consist of 15 subjects that will receive 20 million Allogeneic hMSCs. Group B will receive placebo.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • ISCI / University of Miami Miller School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

In order to participate in this study, a subject must:

1. Provide written informed consent.
2. Subjects age >18 and <75 years at the time of signing the Informed Consent Form.

3. Facetogenic back pain diagnosed using the following diagnostic criteria:

   • The facet joint may be affected by systemic disease, as rheumatoid arthritis and ankylosing spondylitis, or be site of micro traumatic fractures, osteoarthritis, meniscoid entrapment, synovial impingement, joint subluxation, synovial inflammation, loss of cartilage, and mechanical injury.
   • Pain onset at dorsal extension and release at flexion is often considered suggestive for facet pain, even if non-specific, such as maximal tenderness upon deep palpation of posterior elements
   • History of temporary improvement with a medial branch block anesthetic injection of the targeted joints
   • Axial lumbar pain without radicular symptoms
   • Pain on hyperextension, rotation, and lateral bending with physical exam
4. Chronic facetogenic pain (≥ 6 months) in patients that have failed conservative management. (This includes but is not limited to a trial of oral medications, 6 weeks of physical therapy, intra-articular injection of the facet joints, and/or facet joint medial branch neurotomy.)
5. Diagnosis of lumbar facet joint pain confirmed by analgesic injections.
6. Have spinal level L3-4, L4-5 and L5-S1 bilaterally for bilateral pain and same side only for unilateral pain.

Exclusion Criteria:

In order to participate in this study, a subject must not:

1. Previous surgical intervention for back pain
2. Previous mesenchymal stem cell (MSC) injection(s) in to facet joints
3. Use of anticoagulation or NSAIDs within 5 days of the injection
4. MRI finding of severe high grade lumbar stenosis
5. Leg pain exceeding back pain
6. Pain worse with flexion maneuvers
7. Fracture of lumbar vertebrae
8. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood or urine pregnancy test at screening and within 36 hours prior to injection.
9. Inability to perform any of the assessments required for endpoint analysis.
10. Clinically abnormal screening laboratory values.
11. Serious comorbid illness or any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or preclude successful completion of the study.
12. Hypersensitivity to dimethyl sulfoxide (DMSO).
13. Be an organ transplant recipient.
14. Have a clinical history of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma, if recurrence occurs.
15. Have a non-pulmonary condition that limits lifespan to < 1 year.
16. Have a history of drug or alcohol abuse within the past 24 months.
17. Be serum positive for HIV, hepatitis BsAg or Viremic hepatitis C.
18. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Group 1 - Placebo; Group 1 - Five (5) subjects will be treated with a single administration of 1 cc of 1% lidocaine with 1 cc of 2% Ropivicaine and 0.5 cc of betamethasone soluspan (celestone) solution delivered via intra-facet injection. These subjects will be part of the control (Standard care) group.	Drug: Placebo; A single administration of 1 cc of 1% lidocaine with 1 cc of 2% Ropivicaine and 0.5 cc of betamethasone soluspan (celestone) solution delivered via intra-facet injection.
EXPERIMENTAL: Group 2 - Allogeneic Human Mesenchymal Stem Cells (hMSCs); Group 2 - Five (5) subjects will be treated with a single administration of 20 million allogeneic mesenchymal stem cell delivered intra-facet via 6 injections of 1.5 mL per injection, total of 9 to 12ml. These subjects will be part of the experimental group.	Biological: Allogeneic Human Mesenchymal Stem Cells (hMSCs); A single administration of 20 million allogeneic mesenchymal stem cell delivered intra-facet via 6 injections of 1.5 mL per injection, total of 9 to 12ml.; Other Names: stem cells; allo-hMSCs
EXPERIMENTAL: Group A - Allogeneic Human Mesenchymal Stem Cells (hMSCs); Group A will consist of 15 subjects that will receive 20 million Allogeneic hMSCs delivered via lumbar level injection based on pain originator.	Biological: Allogeneic Human Mesenchymal Stem Cells (hMSCs); A single administration of 20 million allogeneic mesenchymal stem cell delivered intra-facet via 6 injections of 1.5 mL per injection, total of 9 to 12ml.; Other Names: stem cells; allo-hMSCs
PLACEBO_COMPARATOR: Group B - Placebo; Group B will consist of 15 subjects who will receive 2% Ropivicaine and 0.5 cc of betamethasone soluspan (celestone) solution via lumbar level injection based on pain originator.	Drug: Placebo; A single administration of 1 cc of 1% lidocaine with 1 cc of 2% Ropivicaine and 0.5 cc of betamethasone soluspan (celestone) solution delivered via intra-facet injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of any treatment-emergent serious adverse events	Incidence (at one-month post injection) of any treatment-emergent serious adverse events.	at one-month post injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in subject quality of life assessment - SF-12	Difference in subject quality of life assessment - SF-12 to assess if there is improvement in health via this health survey.	Baseline, Month 3, and Month 6
Difference in subject quality of life assessment - Oswestry Low Back Pain	Difference in subject quality of life assessment - Oswestry Low Back Pain where the scores are defined by percentage with 0 to 20% showing minimal disability and 81-100% showing severe disabling symptoms.	Baseline, Month 3, and Month 6
Death from any cause.	Death from any cause.	Baseline, Month 3, and Month 6
Change in pain using the Numeric rating scale	Change between baseline and 6 months in pain using the Numeric Rating Scale (NRS) scale. This is assessed on a scale from 0 to 10 with 0 being no pain and 10 being the worst pain.	Baseline and Month 6

Collaborators and Investigators

• Sponsor: Joshua M Hare
• Investigators: Principal Investigator: Andrew Sherman, MD, University of Miami

Publications and helpful links

Helpful Links

• Interdisciplinary Stem Cell Institute website

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2020
• Primary Completion (ANTICIPATED): December 1, 2025
• Study Completion (ANTICIPATED): December 1, 2025

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: March 27, 2018
• First Posted (ACTUAL): April 4, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 20, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: back pain; stem cells
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain
• Other Study ID Numbers: 20180018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No