Evaluation of FDY-5301 in Major Trauma Patients in ICU

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.

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)

Study Overview

• Status: Terminated
• Conditions: ICU Acquired Weakness
• Intervention / Treatment: Drug: FDY-5301; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Torrance, California, United States, 90509
      • Harbor-UCLA Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Shands Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, Harvard Medical School
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FDY-5301 Low Dose (1 mg/kg); 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; FDY-5301 is Sodium Iodide administered as an isotonic solution for intravenous injection with a concentration of 7.2 mg/ml.
Experimental: FDY-5301 High Dose (2 mg/kg); 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; FDY-5301 is Sodium Iodide administered as an isotonic solution for intravenous injection with a concentration of 7.2 mg/ml.
Placebo Comparator: Placebo; 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; Placebo is delivered as a single dose, non-reserved liquid parenteral consisting of a formulation matched compendial saline.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Faraday Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Actual): March 4, 2022
• Study Completion (Actual): March 4, 2022

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: quality of life; muscle function; ICU acquired weakness, PICS, SIRS; Muscle wasting and weakness
• Additional Relevant MeSH Terms: Asthenia
• Other Study ID Numbers: FDY-5301-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No