Covid19
Conditions
Brief summary
This is phase II study to evaluate the safety and efficacy of inhaled Ampion in adults with respiratory distress due to COVID-19
Detailed description
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the pandemic spread of coronavirus disease 2019 (COVID-19), which has a high rate of infection, has a high rate of hospitalization, has overwhelmed healthcare systems, and can be fatal. Ampion is the low molecular weight filtrate of human serum albumin with the in vitro ability to modulate inflammatory cytokine levels. Ampion has the potential to improve clinical outcomes for COVID-19 patients by reducing inflammatory cytokines correlated with the disease and respiratory complications, such as Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). This study aims to evaluate the effects of Ampion on mortality and clinical outcomes in patients with respiratory distress due to COVID-19.
Interventions
BIOLOGICALAmpion
Inhaled Ampion
OTHERPlacebo
Inhaled Placebo
Sponsors
Ampio Pharmaceuticals. Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, ≥ 18 years old 2. Diagnosed with COVID-19, as evaluated by laboratory diagnostic test or diagnosis based on radiological clinical findings. 3. Baseline severity categorization of severe or critical COVID-19 infection per FDA Guidance for developing drugs and biological products for COVID-19 (February 2021): 1. Severe COVID-19: * Symptoms suggestive of severe systemic illness with COVID-19, which could include shortness of breath or respiratory distress * Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air at or PaO2/FiO2 \< 300 2. Critical COVID-19: * Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced cannula at flow rates \> 20 L/min with fraction of oxygen ≥ 0.5) or * Non-invasive mechanical or endotracheal mechanical ventilation 4. Informed consent obtained from the patient or the patient's legal representative.
Exclusion criteria
1. As a result of the medical review and screening investigation, the Principal Investigator considers the patient unfit for the study and/or progression to death is imminent and inevitable irrespective of the provision of treatments. 2. Clinical diagnosis of respiratory failure requiring ECMO and/or therapy is not available due to limitation. 3. Shock defined by systolic blood pressure \<90 mm Hg, or diastolic blood pressure \<60 mm Hg or requiring vasopressors. 4. Multi-organ dysfunction/failure. 5. Patient has severe chronic obstructive or restrictive pulmonary disease (COPD) (as defined by prior pulmonary function tests), chronic renal failure, or significant liver abnormality (e.g., cirrhosis, transplant, etc.). 6. Patient has chronic conditions requiring chemotherapy or immunosuppressive medication. 7. A history of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin is not an exclusion criterion) or ingredients in 5% human albumin (N- acetyltryptophan, sodium caprylate). 8. Prolonged QT interval. 9. Patient has known pregnancy or is currently breastfeeding. 10. Patient planning to become pregnant, or father a child, during the treatment and follow-up period and/or is not willing to remain abstinent or use contraception. 11. Participation in another clinical trial (not including treatments for COVID-19 as approved by the FDA through expanded access, emergency, or compassionate use), or participation in a trial such that enrollment in this study would fall within the time frame of the half-life of the other investigational product(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement of Participants of Ampion Compared to Placebo | Day 28 | Change in ordinal scale from baseline through Day 5 and through Day 28. The WHO's 8 point ordinal scale reflects the highest level of support the subject required on the day being recorded. 0 = No clinical or virological evidence of infection; 1 = no limitation of activities; 2 = limitation of activities; 3 = Hospitalized, no oxygen; 4 = Hospitalized, oxygen by mask or nasal prongs; 5 = Hospitalized, non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, mechanical ventilation; 7 = Hospitalized, ventilation + additional organ support - pressors, RRT, ECMO; 8 = Death. A negative difference in mean score constitutes a reduction in the severity of clinical intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Day 60 | Number of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of treatment of inhalation Ampion compared to Placebo. AEs were assessed based on symptoms as a severity rating of mild, moderate, or severe. The relationship between AE and study drug was determined as either unrelated, possibly related, or related. SAEs are defined as resulting death, life threatening, requires prolonged hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Ampion
Ampion: Inhaled Ampion (8mL) administered four times daily for 5 days | 64 |
| Control Placebo
Placebo: Inhaled Placebo (8mL) administered four times daily for 5 days | 65 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 5 |
Baseline characteristics
| Characteristic | Active | Control | Total |
|---|---|---|---|
| Age, Continuous | 52.9 years STANDARD_DEVIATION 15.2 | 56.9 years STANDARD_DEVIATION 16.6 | 54.9 years STANDARD_DEVIATION 16 |
| Body Mass Index (BMI) | 29.4 kg/m^2 STANDARD_DEVIATION 7.1 | 28.5 kg/m^2 STANDARD_DEVIATION 5.4 | 28.9 kg/m^2 STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 26 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 39 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 36 Participants | 33 Participants | 69 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 29 Participants | 55 Participants |
| Region of Enrollment India | 36 participants | 33 participants | 69 participants |
| Region of Enrollment United States | 28 participants | 32 participants | 60 participants |
| Sex: Female, Male Female | 21 Participants | 26 Participants | 47 Participants |
| Sex: Female, Male Male | 43 Participants | 39 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 64 | 1 / 65 |
| other Total, other adverse events | 21 / 64 | 18 / 65 |
| serious Total, serious adverse events | 2 / 64 | 4 / 65 |
Outcome results
Primary
Clinical Improvement of Participants of Ampion Compared to Placebo
Change in ordinal scale from baseline through Day 5 and through Day 28. The WHO's 8 point ordinal scale reflects the highest level of support the subject required on the day being recorded. 0 = No clinical or virological evidence of infection; 1 = no limitation of activities; 2 = limitation of activities; 3 = Hospitalized, no oxygen; 4 = Hospitalized, oxygen by mask or nasal prongs; 5 = Hospitalized, non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, mechanical ventilation; 7 = Hospitalized, ventilation + additional organ support - pressors, RRT, ECMO; 8 = Death. A negative difference in mean score constitutes a reduction in the severity of clinical intervention.
Time frame: Day 28
Population: Intent to Treat (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Clinical Improvement of Participants of Ampion Compared to Placebo | Day 5 | -0.5 score on a scale | Standard Deviation 0.95 |
| Active | Clinical Improvement of Participants of Ampion Compared to Placebo | Day 28 | -4.1 score on a scale | Standard Deviation 0.63 |
| Control | Clinical Improvement of Participants of Ampion Compared to Placebo | Day 5 | -0.4 score on a scale | Standard Deviation 0.73 |
| Control | Clinical Improvement of Participants of Ampion Compared to Placebo | Day 28 | -4.0 score on a scale | Standard Deviation 0.49 |
Secondary
The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo
Number of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of treatment of inhalation Ampion compared to Placebo. AEs were assessed based on symptoms as a severity rating of mild, moderate, or severe. The relationship between AE and study drug was determined as either unrelated, possibly related, or related. SAEs are defined as resulting death, life threatening, requires prolonged hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect.
Time frame: Day 60
Population: Safety
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active | The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Treatment Emergent Adverse Events (TEAE's) | 21 Participants |
| Active | The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Study Drug Related TEAE's | 0 Participants |
| Active | The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Moderate or Severe TEAE's | 10 Participants |
| Active | The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Serious Adverse Events (SAE's) | 2 Participants |
| Control | The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Serious Adverse Events (SAE's) | 4 Participants |
| Control | The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Treatment Emergent Adverse Events (TEAE's) | 18 Participants |
| Control | The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Moderate or Severe TEAE's | 11 Participants |
| Control | The Number of Participants With Treatment Emergent Adverse Events of Ampion Compared to Placebo | Study Drug Related TEAE's | 1 Participants |