Safety and Efficacy of ULSC on Disease Severity and Steroid Tapering in Participants With Dermatomyositis/ Polymyositis (DM/PM), Also Known as Idiopathic Inflammatory Myopathy (IIM)

A Phase 2-Phase 3, Double-blinded, Randomized, Dose-repeating, Cross-over Study to Assess the Safety and Efficacy of Allogeneic ULSC on Disease Severity and Steroid Tapering in Participants With Dermatomyositis/ Polymyositis (DM/PM)

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.

Inclusion Criteria:

1. Participants will be ≥18 years old.

2. 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).

3. Active disease as defined by any one of the following test results:

   1. Elevated Creatine Kinase (CK) or Aldolase (more than 1.5 x the upper limit of normal) at screening, OR
   2. MRI positive for active, muscle inflammation within 12 weeks prior to screening, OR
   3. EMG read as active myositis within 12 weeks prior to screening, OR
   4. muscle biopsy obtained within 12 weeks of the screening showing active inflammatory disease.

4. Muscle weakness or active cutaneous manifestations of dermatomyositis assessed at Screening and documented with either of the following scores:

   1. Bilateral MMT-8 score of ≤142/150, OR
   2. CDASI Total Activity score of ≥ 7.

5. Participants must be receiving standard of care treatment with one or more immunosuppressants or at least 5 mg prednisone (or corticosteroid equivalent).

   1. Immunosuppressive doses should be stable for at least 12 weeks prior to enrollment. Participants must remain on stable immunosuppressive therapy for the duration of the trial unless discontinuation is warranted due to toxicity or another clinical reason.
   2. Hydroxychloroquine (HCQ) doses should be stable for at least 12 weeks prior to enrollment.
   3. Steroid doses should be stable for at least 4 weeks prior to enrollment. At screening and enrollment, maximum dose allowed is 25 mg/day prednisone (or corticosteroid equivalent).
   4. Allowed immunosuppressants include: methotrexate, azathioprine, mycophenolate, cyclosporine, IVIG, and others to be evaluated at the discretion of the investigator.

6. Participants will either be:

   1. positive for a myositis-associated antibody, OR
   2. will have undergone evaluation to exclude mimics, as deemed appropriate by the Investigator.

   Note: The minimum workup to be performed on all prospective participants to exclude mimics is as standardly followed, which may include:

   • Medical history and physical exam to determine the clinical course and progression of symptoms, the distribution of weakness, and the absence of features of myelopathy, neuropathy, neuromuscular disease, myotonic dystrophy, and congenital myopathy;
   • Elevated Creatine Kinase (CK) or Aldolase levels in blood;
   • Electromyography (EMG) and/or MRI of clinically affected 99+proximal muscle group;
   • Myositis-specific and myositis-associated autoantibodies in blood;
   • Muscle biopsy with characteristic features of IIM and excluding features of muscular dystrophy, metabolic myopathies, drug-induce myopathy, inclusion body myopathy, and necrotizing myopathy;
   • Blood tests for exclusion of HIV, Hepatitis B (HBV), and Hepatitis C (HCV). [Screening tests are done for HIV ELISA, HBs Ag, HBc Ab, and HCV Ab with reflex for HCV RNA (PCR) for exclusion criteria.]

7. Adequate pulmonary function, defined as saturated oxygen (SpO2 ≥ 94%) on room air.

8. Left ventricular ejection fraction (LVEF) ≥ 30% as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed within 8 weeks prior to Screening.

9. Participants must have the ability to comply with the requirements of the study.

10. 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.

11. Participant will have the ability to understand and provide written informed consent.

Exclusion Criteria:

The presence of any of the following criteria excludes a participant from study enrollment:

1. A diagnosis of inclusion body myositis, juvenile DM or PM, myositis in the context of significant autoimmune rheumatologic disease.
2. Diagnosis of IIM as part of an overlap syndrome (except overlap with Sjogren's syndrome).
3. Initiation of Rituxan (rituximab) treatment within 12 weeks of randomization. If participant is already on Rituxan, they must remain on a stable dose throughout the trial.
4. Use of other biologic or investigational drug within 6 half-lives for the agent.
5. Diagnosis of myositis-associated interstitial lung disease or cardiac involvement sufficient to limit participation in the trial in the discretion of the PI.
6. End-stage IIM with irreversible muscle involvement seen on biopsy.
7. Patients with predominant muscle atrophy secondary to uncontrolled or chronic DM or PM, based on clinical, biochemical, and/or radiologic assessment, despite previous optimized treatment.
8. Non-immune myopathies.
9. Cancer associated with myositis.
10. Hypersensitivity to study product components including history of hypersensitivity to dimethyl sulfoxide (DMSO).
11. Pregnant or lactating participants.
12. Concomitant severe cardiac, pulmonary disease, active infection, or other conditions that preclude assessment of safety and efficacy of the study product.
13. Anticipated need for surgery during the trial period.
14. A history of prevalent noncompliance with medical therapy.
15. Recipient of an organ transplant.
16. Neutropenia [absolute neutrophil count <1,800/mm^3 (or <1,000/mm^3 in African-American participants)].
17. Severe impairment in renal function (estimated glomerular filtration rate <30 ml/kg*min).
18. Recent or planned use of vaccination with live attenuated viruses.
19. Active cancer or prior diagnosis of cancer within the past 2 years, except non-melanoma skin cancer and carcinoma in situ of cervix Potential participants diagnosed with IIM <3 years before screening will have mandatory evaluation for cancer.
20. Participants with current or prior hepatitis B infection that could be at risk for reactivation. [For eligibility, screening test results must be HBsAg (DNA) negative and anti-HBc (core antibody total) negative).]
21. Participant with HIV or active Hepatitis C. [For eligibility, the following screening tests must have negative or non-reactive results: HIV ELISA, HCV Ab with reflex for HCV RNA (PCR); if HCV Ab test is positive, exclude if HCV RNA (PCR) is positive.]
22. Condition that would impair an assessment of muscle strength, including neurological disorders such as Parkinson's disease or severe musculoskeletal condition.
23. Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up.