Evaluation of FDY-5301 in Major Trauma Patients in ICU

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of FDY-5301 compared to placebo in major trauma ICU patients at risk of intensive care unit acquired weakness (ICUAW)

The purpose of the trial is to evaluate the efficacy, safety, and PK of FDY-5301 compared to placebo in trauma ICU patients at risk of ICUAW.

Muscle wasting occurs rapidly after major trauma and is often associated with multi-organ failure lasting from a few weeks to a long term disability. It is believed that FDY-5301 may help prevent or treat muscle weakness and organ dysfunction in major trauma patients.

Approximately 252 subjects will be randomized (1:1:1) to receive up to 7 daily bolus IV doses of FDY-5301 at 1 mg/kg or 2 mg/kg, or volume-matched placebo. To ensure equal representation in each group, the randomization will be stratified by the presence or absence of any pelvic or lower limb fractures.

All subjects who satisfy the eligibility criteria will be randomly allocated to one of three treatment groups (FDY-5301 low dose, FDY-5301 high dose, or placebo).

All subjects will be followed for 6 months.

This study will be conducted globally.

Eligibility Criteria:
Inclusion Criteria:

1. Age 18-75 years
2. Major trauma defined as:

   1. thoracic and/or abdominal and/or pelvic injury
   2. necessitating admission to ICU with ventilation anticipated for at least 24 hrs
   3. hemorrhagic shock defined as systolic blood pressure (SBP) \<90 mmHG requiring blood transfusion or base deficit of at least 6mEq/L pre-hospital arrival or within one hour after hospital arrival
3. IRB/IEC-approved consent obtained within 48 hours of first hospital arrival time (i.e., in case of transfers, use time of arrival to first hospital immediately post injury)

Exclusion Criteria:

1. Likely to die within 48 hrs from time of screening
2. Any neurological condition that is perceived at the time of hospital admission as an immediate threat to life or incompatible with good functional recovery and where early limitation or withdrawal of therapy is being considered. For example:

   a. Computed tomography imaging showing evidence of traumatic brain injury (TBI), combined with best representative Glasgow Coma Score (GCS) Motor Score of ≤4 at approximately 24 hrs post injury
3. Evidence of nonreversible spinal cord injury
4. Bilateral femoral fractures
5. Women who are pregnant or breastfeeding. Women of reproductive potential must have a negative serum pregnancy test prior to randomization.
6. Known thyroid disease or thyroid disorder, including subjects on thyroid hormone replacement therapy at the time of randomization
7. Known allergy to iodine
8. Chronic renal disease requiring dialysis
9. Body mass index (BMI) \>40 kg/m2 or \<16 kg/m2
10. Body weight (BW) \>140 kg (or \>309 lb)
11. History or presence of debilitating neurologic or other neuromuscular disease (e.g., spina bifida, amyotrophic lateral sclerosis, multiple sclerosis) at time of randomization
12. Current metastatic cancer
13. Solid organ transplant recipient
14. Evidence of pre-existing sarcopenia defined as having a pre-trauma Clinical Frailty Score (CFS) of ≥5 or based on clinical judgement (e.g. frail by appearance, cachexia, etc.)
15. Use of systemic corticosteroids, immunomodulators, or oncologic chemotherapy within 6 months of randomization (inhaled and topical steroids are allowed)
16. Use of investigational drugs or devices within 30 days of randomization
17. Any clinically significant abnormality identified prior to randomization that in the judgment of the Investigator or Sponsor would preclude safe completion of the study, or confound the anticipated benefit of FDY-5301