Umbilical cord lining stem cell infusions for adults with dermatomyositis or polymyositis

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)

This trial will test whether three IV infusions of umbilical cord lining stem cells help adults with dermatomyositis or polymyositis reduce symptoms and steroid needs.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Restem, LLC. (industry)
• Drugs / interventions: rituximab, methotrexate, prednisone
• Locations: 2 sites (Gainesville, Florida and 1 other locations)
• Trial ID: NCT07160205 on ClinicalTrials.gov

What this trial studies

This phase 2/3 interventional study compares an umbilical cord lining-derived stem cell product (ULSC) to a placebo given as three intravenous infusions of 150 million cells per dose. The trial measures safety of repeated IV ULSC infusions and changes in muscle and skin disease from baseline after each dose and after the full treatment period. For participants on corticosteroids, the study also tracks whether ULSC allows steroid dose reduction or less need for rescue therapy. Eligible adults must meet 2017 EULAR/ACR criteria for idiopathic inflammatory myopathy and have evidence of active muscle or skin inflammation.

Who should consider this trial

Good fit: Adults (18 and older) diagnosed with dermatomyositis or polymyositis by 2017 EULAR/ACR criteria who have active disease and are receiving standard immunosuppressive therapy are the intended participants.

Not a fit: People without active muscle or skin inflammation, those under 18, or those with contraindications to IV cell therapy are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, ULSC could reduce muscle and skin inflammation and allow some patients to taper their steroid doses.

How similar studies have performed: Related umbilical cord- or mesenchymal-derived cell therapies have shown mixed results in autoimmune diseases, and use specifically in dermatomyositis/polymyositis remains relatively novel with limited prior trial evidence.

Eligibility criteria

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.

Where this trial is running

Gainesville, Florida and 1 other locations

• Malcom Randall North Florida/South Georgia VA Medical Center — Gainesville, Florida, United States (RECRUITING)
• Bioresearch Partner — Miami, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Michael Bubb, MD — Malcom Randall North Florida/South Georgia VA Medical Center
• Study coordinator: Clinical Trial Contact

Conditions: Idiopathic Inflammatory Myositis, DERMATOMYOSITIS OR POLYMYOSITIS