Safety and Preliminary Efficacy of ULSC in Facioscapulohumeral Muscular Dystrophy (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)

The goal of this clinical trial is to learn about how an umbilical cord lining-derived stem cell product (ULSC) performs when treating Facioscapulohumeral Muscular Dystrophy (FSHD) 1 or 2. It will assess safety and preliminary efficacy in relieving symptoms of FSHD with ULSC administered in two intravenous (IV) doses of 100 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 FSHD after each dose? Researchers will compare ULSC to placebo.

Participants will:

• Have been diagnosed with FSHD of a Ricci clinical severity score 3 or more.
• Participate in this study for total duration of 21 months with 11 in-person visits and 5 virtual visits.
• Visit the clinic for a total of 4 IV infusions (250 mL) 3 months apart.
• Receive 2 doses of ULSC and 2 doses placebo in either of two sequences, as assigned: ULSC first (Day 0 and Month 3) and placebo second (Month 6 and Month 9), or placebo first (Day 0 and Month 3) and ULSC second (Month 6 and Month 9).
• Return for follow-up visits after each dose and up to 12 months after final dose.

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.