Evaluation of FDY-5301 in Major Trauma Patients in ICU

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Intravenous FDY-5301 for the Prevention and Treatment of ICU Acquired Weakness in Major Trauma Patients.

Conditions
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ICU Acquired Weakness

Intervention / Treatment
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* Drug: FDY-5301
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Major trauma defined as: thoracic and/or abdominal and/or pelvic injury necessitating admission to ICU with ventilation anticipated for at least 24 hrs 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 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: Likely to die within 48 hrs from time of screening 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 Evidence of nonreversible spinal cord injury Bilateral femoral fractures Women who are pregnant or breastfeeding. Women of reproductive potential must have a negative serum pregnancy test prior to randomization. Known thyroid disease or thyroid disorder, including subjects on thyroid hormone replacement therapy at the time of randomization Known allergy to iodine Chronic renal disease requiring dialysis Body mass index (BMI) >40 kg/m2 or <16 kg/m2 Body weight (BW) >140 kg (or >309 lb) History or presence of debilitating neurologic or other neuromuscular disease (e.g., spina bifida, amyotrophic lateral sclerosis, multiple sclerosis) at time of randomization Current metastatic cancer Solid organ transplant recipient 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.) Use of systemic corticosteroids, immunomodulators, or oncologic chemotherapy within 6 months of randomization (inhaled and topical steroids are allowed) Use of investigational drugs or devices within 30 days of randomization 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All subjects who fulfill all study edibility criteria will be randomized to receive one of the 3 treatments.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FDY-5301 Low Dose (1 mg/kg)<br>FDY-5301 will be administered intravenously once daily for up to 7 days. Dosage will be determined on a body weight basis, according to treatment assignment and using the subject's body weight (estimated or actual) determined at screening. | Drug: FDY-5301<br>* FDY-5301 is Sodium Iodide administered as an isotonic solution for intravenous injection with a concentration of 7.2 mg/ml.<br>|
| Experimental: FDY-5301 High Dose (2 mg/kg)<br>FDY-5301 will be administered intravenously once daily for up to 7 days. Dosage will be determined on a body weight basis, according to treatment assignment and using the subject's body weight (estimated or actual) determined at screening. | Drug: FDY-5301<br>* FDY-5301 is Sodium Iodide administered as an isotonic solution for intravenous injection with a concentration of 7.2 mg/ml.<br>|
| Placebo Comparator: Placebo<br>Placebo will be administered intravenously once daily for up to 7 days. Dosage will be determined on a body weight basis, according to treatment assignment and using the subject's body weight (estimated or actual) determined at screening. Other Names: Saline | Other: Placebo<br>* Placebo is delivered as a single dose, non-reserved liquid parenteral consisting of a formulation matched compendial saline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chelsea Critical Care Physical Assessment Tool | Chelsea Critical Care Physical Assessment Tool (CPAx) total score at Day 10, or hospital discharge, whichever occurs first. The Chelsea Critical Care Physical Assessment Tool components will be graded on a 6-point scale from dependent to independent (0 to 5). The individual values will be collated giving a total score out of 50. A higher score indicates a better outcome. | Day 10 or hospital discharge, whichever occurs first. | 
| Organ Dysfunction Total Time to Recovery | Organ dysfunction total time to recovery (TTR) until Day 28 | Day 28 or hospital discharge, whichever occurs first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medical Research Council Sum Score | Medical Research Council Sum Score (MRC-SS) at Day 28, or hospital discharge, whichever occurs first. The Medical Research Council Sum Score measures global peripheral muscle strength which ranges from 0 (complete paralysis) to 60 (normal strength). A higher score indicates a better outcome. | Day 28, or hospital discharge, whichever occurs first | 
| Sequential Organ Failure Assessment Score | The Sequential Organ Failure Assessment (SOFA) is a scoring system that assesses the performance of several organ systems in the body and assigns a score based on the data obtained in each category, this is scored during the ICU stay. The full-length Sequential Organ Failure Assessment score ranges from 0 to 24. A higher score indicates a worse outcome. | ICU hospital stay until Day 28 or ICU discharge if earlier | 
| Overall Survival at Day 28 | Confirmation of survival status will be obtained by speaking directly with subject, via medical records, or public health records. | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ICU acquired weakness, PICS, SIRS, Muscle wasting and weakness, muscle function, quality of life