The goal of this clinical trial is to learn about how an umbilical cord lining-derived stem cell (ULSC) product performs when treating Dermatomyositis/Polymyositis (DM/PM), also known as idiopathic inflammatory myopathy (IIM) in adults. It will assess safety and efficacy in relieving symptoms of DM/PM with ULSC administered in three intravenous (IV) doses of 150 million cells per dose.
The main questions that this study plans to answer are:
* Is ULSC as safe as placebo (a look-alike saline without cells) in repeated IV infusion? * Does ULSC improve symptoms of DM/PM after three doses? Researchers will compare ULSC to placebo and evaluate changes from baseline (before first dose) to after each dose and after all three doses are completed per treatment study period. * For participants undergoing steroid (e.g., prednisone) therapy for DM/PM, does ULSC allow their steroid dose to be reduced? Does ULSC reduce need for rescue therapy?
Participants will have been diagnosed with either DM or PM:
* Diagnosed according to the EULAR/ACR 2017 Classification Criteria for idiopathic inflammatory myositis (IIM), which includes DM and PM. * Positive for myositis-associated antibody or undergone evaluation to exclude mimics.
Participants in this study will:
* Participate for total of 25 months with 15 in-person clinic visits and 8 virtual visits on phone or video call. * Receive both ULSC and placebo for a total of 6 IV infusions (260 mL) 3 months apart. * Receive 3 doses of ULSC and 3 doses placebo in either of two sequences, as assigned: ULSC first and placebo second, or placebo first and ULSC second. * If undergoing steroid therapy, will have steroid dose taper prescribing lower doses starting two weeks after the second infusion. * Return for follow-up visits after each dose and up to 12 months after final dose. * Have follow-ups including self-reported questionnaires, physical exam, muscle strength and endurance tests, blood tests, pulmonary function tests, and other assessments.
Participants will be ≥18 years old.
Diagnosis of idiopathic inflammatory myositis (IIM) based on 2017 EULAR/ACR Classification Criteria for adult IIM, corresponding to a score of ≥ 5.5 (≥ 6.7 with muscle biopsy).
Elevated Creatine Kinase (CK) or Aldolase (more than 1.5 x the upper limit of normal) at screening, OR
MRI positive for active, muscle inflammation within 12 weeks prior to screening, OR
Adequate pulmonary function, defined as saturated oxygen (SpO2 ≥ 94%) on room air.
Left ventricular ejection fraction (LVEF) ≥ 30% as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed within 8 weeks prior to Screening.
Participants must have the ability to comply with the requirements of the study.
All participants of reproductive age/capacity will be required to use adequate contraception, defined as at least one form of a highly effective contraceptive (i.e., condoms, hormonal birth control, IUD), with any partners during the study period and for at least three months beyond the study period, for safety.
Crossover
ULSC (1.5 x 10^8 cells/dose)
Biological/VaccineAllogeneic umbilical-cord lining stem cells (ULSC) are cryopreserved and supplied in vials to be thawed and prepared for infusion at point of use. Each dose of 1.5 x 10\^8 ULSC will be added into 250 sterile saline IV bag for infusion (total volume of 260 mL volume).
Placebo (no cells)
Biological/VaccineThe Placebo will be 250 ml sterile saline with vehicle (total volume of 260 mL) IV bag for infusion.
Safety based on Adverse Events (AEs) and Serious Adverse Events (SAEs) that begin during or following treatment infusion.
Cumulative listing of all AEs/SAEs per cohort with descriptive statistics for categorical variables and count variables to compare between ULSC and Placebo, with emphasis on All SAEs and AEs/SAEs suspected to be treatment infusion-related.
Efficacy based on Total Improvement Score (TIS, expressed as continuous variable) in the 2016 ACR/EULAR Myositis Response Criteria
Total Improvement Score (TIS) as continuous variable (scale of 0 to 100 points) will be assessed; TIS is a weighted average of the sub-scores in the 6 core set measures that comprise the validated outcome measure in the 2016 ACR/EULAR Myositis Response Criteria.
Need for Rescue Therapy (Incidence)
The incidence of need for rescue therapy will be assessed by the number of participants that require administration of rescue therapy.
Need for Rescue Therapy (Time)
Need for rescue therapy will be assessed in terms of the time to rescue therapy, i.e. time from the first dose of study treatment to the first administration of rescue therapy required.
Glucocorticoid Dose (prednisone equivalents per day) Tapering
Changes from baseline in glucocorticoid dose expressed in prednisone equivalents (mg/day) will be assessed as a measure of steroid tapering over time.
Total Improvement Score (TIS) improvement category (minimal, moderate, or major improvement) in the 2016 ACR/EULAR Myositis Response Criteria
Response relative to baseline will be assessed in terms of Total improvement category (minimal TIS ≥20, moderate TIS ≥40, or major TIS ≥60). TIS is a weighted average of the sub-scores in the 6 core set measures that comprise the validated outcome measure in the 2016 ACR/EULAR Myositis Response Criteria.
Erythrocyte Sedimentation Rate (ESR) - systemic inflammatory/immune marker
Changes in erythrocyte sedimentation rate (ESR, mm/hour) will be measured as a systemic inflammatory/immune marker. The ESR lab test measures the rate at which red blood cells (erythrocytes) settle in a vertical blood tube over one hour. During inflammation, blood proteins increase that result in ESR increase.
C-Reactive Protein (CRP) - systemic inflammatory/immune marker
Changes in C-Reactive Protein (CRP, mg/L) will be measured as a systemic inflammatory/immune marker in serum samples using a high-sensitivity CRP (HS-CRP) imunoturbidimetric test.
TGF-β1 - systemic inflammatory/immune marker
Changes in cytokine levels of transforming growth factor-beta 1 (TGF-β1, pg/mL) will be measured as a systemic inflammatory/immune marker in plasma samples using a Luminex-based assay panel.
TNF-α - systemic inflammatory/immune marker
Changes in cytokine levels of tumor necrosis factor-alpha (TNF-α, pg/mL) will be measured as a systemic inflammatory/immune marker in plasma samples using a Luminex-based assay panel.
Click on the lead sponsor to view all of their trials.
