ICU Acquired Weakness
Conditions
Keywords
ICU acquired weakness, PICS, SIRS, Muscle wasting and weakness, muscle function, quality of life
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.
Interventions
DRUGFDY-5301
FDY-5301 is Sodium Iodide administered as an isotonic solution for intravenous injection with a concentration of 7.2 mg/ml.
OTHERPlacebo
Placebo is delivered as a single dose, non-reserved liquid parenteral consisting of a formulation matched compendial saline.
Sponsors
Faraday Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind study where all study staff and participants are blinded to whether the patient receives active drug or placebo.
Intervention model description
All subjects who fulfill all study edibility criteria will be randomized to receive one of the 3 treatments.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chelsea Critical Care Physical Assessment Tool | Day 10 or hospital discharge, whichever occurs first. | 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. |
| Organ Dysfunction Total Time to Recovery | Day 28 or hospital discharge, whichever occurs first. | Organ dysfunction total time to recovery (TTR) until Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Medical Research Council Sum Score | Day 28, or hospital discharge, whichever occurs first | 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. |
| Sequential Organ Failure Assessment Score | ICU hospital stay until Day 28 or ICU discharge if earlier | 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. |
| Overall Survival at Day 28 | Day 28 | Confirmation of survival status will be obtained by speaking directly with subject, via medical records, or public health records. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FDY-5301 Low Dose 1 mg/kg FDY-5301 will be administered intravenously once daily for up to 7 days. | 2 |
| FDY-5301 High Dose 2 mg/kg FDY-5301 will be administered intravenously once daily for up to 7 days. | 2 |
| Placebo Placebo will be administered intravenously once daily for up to 7 days. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | FDY-5301 High Dose | Placebo | Total | FDY-5301 Low Dose |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 4 Participants | 8 Participants | 2 Participants |
| Age, Continuous | 32.5 years | 25.25 years | 29.25 years | 34 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 5 Participants | 0 Participants |
| Region of Enrollment United States | 2 participants | 4 participants | 8 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 8 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 4 / 4 |
| serious Total, serious adverse events | 1 / 2 | 1 / 2 | 0 / 4 |
Outcome results
Primary
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.
Time frame: Day 10 or hospital discharge, whichever occurs first.
Population: Overall number of participants analyzed for CPAx data includes only those who have Day 10 CPAx scores. The small number of subjects enrolled in each of the groups preclude interpretation of the CPAx data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FDY-5301 Low Dose | Chelsea Critical Care Physical Assessment Tool | 9 Score on a scale |
| FDY-5301 High Dose | Chelsea Critical Care Physical Assessment Tool | 31.5 Score on a scale |
| Placebo | Chelsea Critical Care Physical Assessment Tool | 11 Score on a scale |
Primary
Organ Dysfunction Total Time to Recovery
Organ dysfunction total time to recovery (TTR) until Day 28
Time frame: Day 28 or hospital discharge, whichever occurs first.
Population: The small number of subjects enrolled in each of the groups preclude interpretation of the organ dysfunction total TTR data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FDY-5301 Low Dose | Organ Dysfunction Total Time to Recovery | 8.5 Days |
| FDY-5301 High Dose | Organ Dysfunction Total Time to Recovery | 4 Days |
| Placebo | Organ Dysfunction Total Time to Recovery | 6 Days |
Secondary
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.
Time frame: Day 28, or hospital discharge, whichever occurs first
Population: The small number of subjects enrolled in each of the groups preclude interpretation of the MRC-SS data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FDY-5301 Low Dose | Medical Research Council Sum Score | 20 Score on a scale |
| Placebo | Medical Research Council Sum Score | 31.5 Score on a scale |
Secondary
Overall Survival at Day 28
Confirmation of survival status will be obtained by speaking directly with subject, via medical records, or public health records.
Time frame: Day 28
Population: The small number of subjects enrolled in each of the groups preclude interpretation of the Overall Survival at Day 28 data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FDY-5301 Low Dose | Overall Survival at Day 28 | 2 Participants |
| FDY-5301 High Dose | Overall Survival at Day 28 | 2 Participants |
| Placebo | Overall Survival at Day 28 | 4 Participants |
Secondary
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.
Time frame: ICU hospital stay until Day 28 or ICU discharge if earlier
Population: The small number of subjects enrolled in each of the groups preclude interpretation of the SOFA data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FDY-5301 Low Dose | Sequential Organ Failure Assessment Score | 7.5 Score on a scale |
| FDY-5301 High Dose | Sequential Organ Failure Assessment Score | 6.5 Score on a scale |
| Placebo | Sequential Organ Failure Assessment Score | 7.5 Score on a scale |