Clinical trial NCT04430283: Evaluation of FDY-5301 in Major Trauma Patients in ICU
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: ICU Acquired Weakness
Keywords: ICU acquired weakness, PICS, SIRS
Muscle wasting and weakness
muscle function
quality of life
Lead sponsor: Faraday Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-12
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All subjects who fulfill all study edibility criteria will be randomized to receive one of the 3 treatments.
Primary purpose: PREVENTION

Brief summary: 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: 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

Primary outcomes:
measure: Chelsea Critical Care Physical Assessment Tool
timeFrame: Day 10 or hospital discharge, whichever occurs first.
measure: Organ Dysfunction Total Time to Recovery
timeFrame: Day 28 or hospital discharge, whichever occurs first.
Secondary outcomes:
measure: Medical Research Council Sum Score
timeFrame: Day 28, or hospital discharge, whichever occurs first
measure: Sequential Organ Failure Assessment Score
timeFrame: ICU hospital stay until Day 28 or ICU discharge if earlier
measure: Overall Survival at Day 28
timeFrame: Day 28
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida Health Shands Hospital
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital, Harvard Medical School
state: Massachusetts
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Seattle
country: United States
facility: Harborview
state: Washington
Study officials:
References: