Umbilical cord lining stem cell treatment for FSHD

A Phase 1, Double-blinded, Randomized, Dose-repeating, Placebo-controlled, Cross-over Study to Assess the Safety and Preliminary Efficacy of Allogeneic ULSC on Disease Severity in Facioscapulohumeral Muscular Dystrophy (FSHD)

This trial will try two intravenous doses of umbilical cord lining–derived stem cells (ULSC) versus placebo to see if they are safe and help people aged 15+ with genetically confirmed FSHD and moderate disease (Ricci score ≥3).

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 15 Years and up
• Sex: All
• Sponsor: Restem, LLC. (Industry-sponsored)
• Locations: 1 site (Palo Alto, California)
• Trial ID: NCT07086521 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, placebo-controlled study testing safety and preliminary signs of benefit of ULSC in people with genetically confirmed FSHD type 1 or 2. Participants receive four 250 mL IV infusions given three months apart, with two doses containing 100 million ULSC cells and two doses placebo delivered in one of two assigned sequences. The total participation time is about 21 months and includes 11 in-person visits and 5 virtual visits, with clinical and imaging assessments including MRI. Safety after repeated IV infusions and symptom changes after each dose are the main outcomes compared between ULSC and placebo.

Who should consider this trial

Good fit: Ideal candidates are people aged 15 or older with genetically confirmed FSHD1 or FSHD2, a Ricci clinical severity score of 3 or higher, who are independently ambulatory and able to comply with MRI and study visits.

Not a fit: People with mild FSHD (Ricci score <3), who are non‑ambulatory, under age 15, or who cannot meet MRI or visit requirements are unlikely to qualify or receive benefit from this study.

Why it matters

Potential benefit: If successful, ULSC could reduce symptoms or improve muscle function in people with moderate FSHD and provide a new therapeutic option.

How similar studies have performed: Using umbilical cord–derived cells for FSHD is largely novel; some early-phase and preclinical work suggests safety of cord‑derived cells in other conditions, but efficacy in FSHD remains unproven.

Eligibility criteria

Inclusion Criteria:

* Participants will be ≥15 years old.
* Diagnosis of genetically confirmed FHSD 1 or FSHD 2.
* Participants should have a Ricci clinical severity score of ≥3 (range is out of 0-10), at screening, and must be independently ambulatory at the time of the study.
* Participant will have the ability to comply with the requirements of the study, including MRI.
* All participants of reproductive age/capacity will be required to use adequate contraception, defined as two forms of highly effective contraceptives, with any partners during the study period and for at least three months beyond the study period for safety.
* Participant will have the ability to understand and provide written informed consent.
* For those participants who are on drug(s) or supplements that may affect muscle function, as determined by the Investigator, participants must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study. This includes the following drug category:

  o Immunomodulatory agents, including targeted biological therapies.
* Reduced upper arm strength as measured by the Performance of Upper Limb score of ≤5.
* Current and up-to-date immunizations.
* Total relative reachable surface area (RSA) (Q1-Q4) without weight in the dominant upper extremity assessed by reachable workspace (RWS) ≥ 0.2 and ≤ 0.7.
* No contraindications to MRI.
* Hematocrit of ≤ 50%
* Prostate-specific antigen ≤ 4.0 ng/mL (or ≤ 3.0 ng/mL if the participant has a first-degree relative with prostate cancer)
* Fasting blood glucose \<126 mg/dL

Exclusion Criteria:

* Hypersensitivity to study product components including history of hypersensitivity to dimethyl sulfoxide (DMSO).
* Active cancer or prior diagnosis of cancer within the past year (patients with basal and squamous cell cancer of skin will not be excluded).
* Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up.
* Treatment with an investigational product within three months prior to randomization.
* Known active opportunistic or life-threatening infections including Human Immunodeficiency virus (HIV) and hepatitis B or C.
* Known active or inactive tuberculosis infection.
* Use of a product that putatively enhances muscle growth or activity on a chronic basis within 4 weeks before baseline
* Orally administered cytochrome P450 (CYP3A4) substrates and multidrug and toxin extrusion (MATE) and organic anion transporter (OAT)3 substrates are not permitted as concomitant therapy.
* Statin treatment initiation or significant adjustment to statin regimen within 3 months before baseline (stable, chronic statin use is permissible).
* Rapamycin treatment within 3 months before baseline.
* Evidence of an alternative diagnosis other than FSHD or a coexisting myopathy or dystrophy, based on prior muscle biopsy or other available investigations.
* Muscle biopsy within 30 days before baseline.
* A systolic blood pressure over 160 or a diastolic pressure over 100
* Heavy alcohol use (greater than 50g/day)
* Current testosterone or HGH use
* Current use of medications that interfere with the growth hormone or gonadal endocrine axis.
* Pregnant of lactating participants.
* Concomitant severe cardiac, pulmonary disease, active infection, or other conditions that preclude assessment of safety and efficacy of the study product.
* Anticipated need for surgery during the trial period.
* A history of prevalent noncompliance with medical therapy.
* Recipient of an organ transplant.
* Neutropenia (absolute neutrophil count \<1,800/mm\^3 \[or \<1,000/mm\^3 in African-American participants\]).
* Severe impairment in renal function (estimated glomerular filtration rate \<30 ml/kg\*min).
* Recent of planned use of vaccination with live attenuated viruses.
* Condition that would impair an assessment of muscle strength, including neurological disorders such as Parkinson's disease or severe musculoskeletal condition.

Where this trial is running

Palo Alto, California

• Stanford Neuroscience Health Center — Palo Alto, California, United States (Recruiting)

Study contacts

• Principal investigator: John W Day, MD, PhD — Stanford University, School of Medicine, Neuromuscular Research Division

Conditions FSHD - Facioscapulohumeral Muscular Dystrophy