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

ConditionFSHD - Facioscapulohumeral Muscular Dystrophy

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age15+

SponsorRestem, LLC.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Crossover

Treatments tested in this trial

ULSC
Biological/Vaccine
Allogeneic 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 x 10\^8 ULSC will be added to into 250 sterile saline for infusion (total volume of 260 mL volume).
Placebo
Biological/Vaccine
The Placebo will be 250 ml of sterile saline for IV administration.

Treatment groups

16 Participants

are divided into 2 treatment groups

Group A: Group 1: ULSC first; Placebo secondExperimental treatment 2 interventions

Group B: Group 2: Placebo first; ULSC secondExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Adverse Events (AE) and Serious Adverse Events (SAEs) that begin during or following treatment infusion.

Cumulative listing of all AEs/SAEs with descriptive statistics for categorical variables and count variables with emphasis on All SAEs and AEs/SAEs suspected to be treatment infusion-related.

Time frame

7 days and 30 days after each infusion, as well as 6 months after the final dose for each period (Month 9 and Month 15).

Secondary outcomes

Facioscapulohumeral Muscular Dystrophy Composite Outcome Measure (FSHD-COM)

FSHD-COM score, which is based on objective markers of disease activity, will be assessed. The FSHD-COM is an 18-item physician-administered instrument. The body regions represented are leg function, shoulder and arm function, trunk function, hand function, and balance/mobility. Each component is scored on a 0-4 scale (0 = normal) out of a possible 72 points.

Time frame

Baseline, 7, and 30 days after each infusion, as well as 6 months after the final dose for each period (Month 9 and Month 15).

Muscle Fat Fraction (MFF)

Change from baseline in Muscle Fat Fraction (MFF, %) as a measure of infiltration of fat in muscle; this is assessed by Musculoskeletal (MSK) Magnetic Resonance Imaging (MRI)

Time frame

Baseline to Month 6 and Month 12.

Lean Muscle Volume (LMV)

Change from baseline in Lean Muscle Volume (LMV, cu cm or Liter) as a measure of infiltration of fat in muscle; this is assessed by Musculoskeletal (MSK) Magnetic Resonance Imaging (MRI).

Time frame

Baseline to Month 6 and Month 12.

Patient-Reported Quality of Life Outcome Assessed by PROMIS-57

Change in level of disease activity as reflected in patient-reported quality of life outcome assessed by using PROMIS-57. The PROMIS-57 is a questionnaire developed by the NIH PROMIS initiative that generates scores for physical function and the impact of physical limitations on daily life.

Time frame

Between baseline and the 6-month timepoint (prior to third administration), and between the 6-month and 12-month timepoints.

Other outcomes

Iowa Oral Performance Instrument (IOPI) Scores

Change from baseline in IOPIs at each clinical visit. Researchers have used this device in many studies to measure oral strength (kPa) with excellent inter-rater reliability.

Time frame

At each clinical visit from baseline and up to Month 12.

Cardiopulmonary Exercise Testing (CPET) Assessment

Change from baseline in the Rating of Perceived Exertion (RPE, Borg Scale) assessed in CPET at each clinical visit.

Time frame

From baseline to Month 6 and Month 12.

Tissue Oxygenation Assessed by Near-Infrared Spectroscopy (NIRS) during Cardiopulmonary Exercise Testing (CPET)

Change from baseline of tissue oxygenation during CPET with noninvasive and continuous monitoring of regional tissue oxygenation (rSO2) using NIRS at each clinical visit.

Time frame

From baseline to Month 6 and Month 12.

FSHD-COM Subscales

Change from baseline for FSHD-COM subscales assessed at each clinical visit.

Time frame

At each clinical visit from baseline and up to Month 15.