COVID-19
Conditions
Keywords
Corona Virus Disease (COVID-19), Niclosamide, Antiviral, Immunomodulator, Oral Niclosamide, Infection, Acute Respiratory Distress Syndrome (ARDS), Cytokine dysregulation, Virus, Viral, anthelmintic, anti-inflammatory, bronchodilator, antineoplastic, ANA001, Moderate COVID-19, ARDS, Acute Respiratory Distress Syndrome, Hospitalized COVID-19
Brief summary
Study of ANA001 in Moderate and Severe COVID-19 Patients
Detailed description
This is a 2 part, Phase 2/3 multi-center, double blinded, placebo-controlled study to assess the safety, tolerability, and efficacy of oral niclosamide (ANA001) in moderate and severe hospitalized COVID-19 patients compared to placebo.
Interventions
DRUGNiclosamide
Niclosamide is an antihelmintic with in-vitro antiviral activity
DRUGPlacebo
Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients
Sponsors
NeuroBo 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
Key Inclusion Criteria: 1. Provide written informed consent prior to performing study procedures 2. Hospitalized. 3. Male or female ≥18 years of age 4. Positive for severe acute respiratory syndrome coronavirus 2 5. Presence of symptoms of lower respiratory tract infection (LRTI) including at least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, or more significant lower respiratory tract symptoms, including shortness of breath 6. At least 1 of the following: respiratory rate (RR) ≥20 breaths per minute, room air oxygen saturation (SpO2) \<98%, requirement for supplemental oxygen, heart rate (HR) ≥90 beats per minute, or temperature \>38.3°C 7. Women of childbearing potential must agree to abstinent or use at least 1 form of contraception not including hormonal contraception from the day of screening through Day 30 Key
Exclusion criteria
1. Hospitalized but no longer requires ongoing inpatient care (i.e., discharge is anticipated in ≤24 hours) 2. Patient is not anticipated to survive \>48 hours OR is under palliative care 3. Evidence of critical illness, defined by at least 1 of the following: * Respiratory failure requiring at least 1 of the following: 1. Endotracheal intubation and mechanical ventilation, oxygen delivered by high flow nasal cannula 2. Noninvasive positive pressure ventilation (NIPVV), OR 3. Extracorporeal membrane oxygenation (ECMO) or clinical diagnosis of respiratory failure * Shock (defined by systolic blood pressure (BP) \<90 mm Hg, or diastolic blood pressure (BP) \<60 mm Hg or requiring vasopressors), OR * Multi-organ dysfunction/failure 4. Severe central nervous system (CNS) conditions 5. Chronic kidney disease requiring dialysis 6. Known allergy to the study drug or salicylate containing medications. 7. Suspected and/or confirmed pregnancy or breastfeeding 8. Current or planned participation in any other clinical trial of a treatment being developed under a US investigational new drug (IND) or emergency use authorization (EUA). 9. Patients receiving chemotherapeutic agents and/or immunomodulators (including monoclonal antibodies (Mabs) or plasma transfusions) for chronic disease conditions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Experiencing TEAEs | Randomization to Day 60 | Incidence of Treatment Emergent Adverse Events (TEAEs) |
| Number of Subjects Experiencing TESAEs | Randomization to Day 60 | Incidence of Treatment Emergent Serious Adverse Events (TESAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to 2-point Improvement WHO Clinical Improvement Scale | Randomization to Day 60 | Median Time to 2-point Improvement in WHO Ordinal Scale for Clinical Improvement. This is a 9 point ordinal scale with 0 indicating No clinical or virological evidence of infection and 8 indicating Death |
| Median Time to Resolution of COVID-19 Symptoms | Randomization to Day 60 | Median time (in days) to resolution of subjective symptoms assessed by the Investigator to be potentially due to COVID-19 including: fever, cough (productive or non-productive), sore throat, malaise, headache, muscle pain, gastrointestinal symptoms (i.e., nausea, vomiting, or diarrhea), shortness of breath (with or without exertion), and respiratory distress |
| AUC 0-t (h*ng/mL) | Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose. | Area under the drug concentration (h\*ng/mL) (AUC) vs time curve on Days 1 and 2 |
| Cmax (ng/mL) | Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose. | Maximum post dose plasma drug concentration on \[Cmax (ng/mL)\] Days 1 and 2 |
| Tmax (h) | Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose. | Time to maximum post dose plasma drug concentration on \[Tmax (h)\] Days 1 and 2 |
| Median Time to Time-to-Viral Load Undetectable | Randomization to Day 60 | Median number of days to viral load undetectable by nasopharyngeal (NP) swab |
| Median Time to Hospital Discharge | Randomization to Day 60 | Median time until patient is discharged from hospital. Discharge is defined as a score of 1 or 2 in the WHO Ordinal Scale for Clinical Improvement. This is a 9 point ordinal scale with 0 indicating No clinical or virological evidence of infection and 8 indicating Death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ANA001 Subjects in the ANA001 treatment arm will receive 1,000 mg (4 capsules; 250 mg each) by mouth twice per day for 7 consecutive days with a meal. If the participant requires mechanical ventilation over the course of the study, ANA001 may be administered via nasogastric (NG), percutaneous endoscopic gastrostomy (PEG) or orogastric (OG) tube and, if possible, should be administered with a scheduled nasogastric (NG) or orogastric (OG) feeding.
Niclosamide: Niclosamide is an antihelmintic with in-vitro antiviral activity | 25 |
| Matching Placebo Subjects in the comparator arm will receive matching placebo (hydroxypropylmethylcellulose (HPMC)) (4 capsules, by mouth twice a day) for the 7-day treatment duration.
Placebo: Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Not Dosed | 2 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | ANA001 | Matching Placebo | Total |
|---|---|---|---|
| Age, Customized 18 -<40 Years | 5 Participants | 3 Participants | 8 Participants |
| Age, Customized 40-<65 Years | 13 Participants | 15 Participants | 28 Participants |
| Age, Customized >/=65 Years | 7 Participants | 6 Participants | 13 Participants |
| Baseline WHO Ordinal Scale for Clinical Improvement Baseline World Health Organisation (WHO) Ordinal Scale for Clinical Improvement= 4 | 3 Participants | 4 Participants | 7 Participants |
| Baseline WHO Ordinal Scale for Clinical Improvement Baseline World Health Organisation (WHO) Ordinal Scale for Clinical Improvement = 5 | 19 Participants | 17 Participants | 36 Participants |
| Baseline WHO Ordinal Scale for Clinical Improvement Baseline World Health Organisation (WHO) Ordinal Scale for Clinical Improvement = 6 | 1 Participants | 2 Participants | 3 Participants |
| Baseline WHO Ordinal Scale for Clinical Improvement Baseline World Health Organisation (WHO) Ordinal Scale for Clinical Improvement = Missing | 2 Participants | 1 Participants | 3 Participants |
| Days from First COVID-19 Symptom to Randomisation | 7.6 Days STANDARD_DEVIATION 4.12 | 7.7 Days STANDARD_DEVIATION 3.53 | 7.7 Days STANDARD_DEVIATION 3.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 18 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 20 Participants | 18 Participants | 38 Participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Male | 12 Participants | 14 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 22 | 3 / 23 |
| other Total, other adverse events | 16 / 22 | 12 / 23 |
| serious Total, serious adverse events | 3 / 22 | 6 / 23 |
Outcome results
Primary
Number of Subjects Experiencing TEAEs
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time frame: Randomization to Day 60
Population: Safety Analysis Set: Includes all randomized participants, classified according to the actual treatment received regardless of randomization assignment, who received any amount of study drug and have at least one post-baseline safety evaluation. This is the analysis population for all planned safety analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ANA001 | Number of Subjects Experiencing TEAEs | No. of Subjects with any TEAE | 16 Participants |
| ANA001 | Number of Subjects Experiencing TEAEs | No. of Subjects with Mild (Grade 1) TEAEs | 9 Participants |
| ANA001 | Number of Subjects Experiencing TEAEs | No. of Subjects with Moderate (Grade 2) TEAEs | 5 Participants |
| ANA001 | Number of Subjects Experiencing TEAEs | No. of Subjects with Severe (Grade 3) TEAEs | 0 Participants |
| ANA001 | Number of Subjects Experiencing TEAEs | No. of Subjects with Life-Threatening (Grade 4) TEAEs | 0 Participants |
| ANA001 | Number of Subjects Experiencing TEAEs | No. of Subjects with Death (Grade 5) TEAEs | 2 Participants |
| Matching Placebo | Number of Subjects Experiencing TEAEs | No. of Subjects with Life-Threatening (Grade 4) TEAEs | 1 Participants |
| Matching Placebo | Number of Subjects Experiencing TEAEs | No. of Subjects with any TEAE | 12 Participants |
| Matching Placebo | Number of Subjects Experiencing TEAEs | No. of Subjects with Severe (Grade 3) TEAEs | 2 Participants |
| Matching Placebo | Number of Subjects Experiencing TEAEs | No. of Subjects with Mild (Grade 1) TEAEs | 2 Participants |
| Matching Placebo | Number of Subjects Experiencing TEAEs | No. of Subjects with Death (Grade 5) TEAEs | 3 Participants |
| Matching Placebo | Number of Subjects Experiencing TEAEs | No. of Subjects with Moderate (Grade 2) TEAEs | 4 Participants |
Primary
Number of Subjects Experiencing TESAEs
Incidence of Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: Randomization to Day 60
Population: Safety Analysis Set: Includes all randomized participants, classified according to the actual treatment received regardless of randomization assignment, who received any amount of study drug and have at least one post-baseline safety evaluation. This is the analysis population for all planned safety analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ANA001 | Number of Subjects Experiencing TESAEs | 3 Participants |
| Matching Placebo | Number of Subjects Experiencing TESAEs | 6 Participants |
Secondary
AUC 0-t (h*ng/mL)
Area under the drug concentration (h\*ng/mL) (AUC) vs time curve on Days 1 and 2
Time frame: Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose.
Population: Day 1 data only available for 7 subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ANA001 | AUC 0-t (h*ng/mL) | Day 1: AUC 0-t (h*ng/mL) | 1728.6 h*ng/mL | Standard Deviation 1410.21 |
| ANA001 | AUC 0-t (h*ng/mL) | Day 2: AUC 0-t (h*ng/mL) | 2839.0 h*ng/mL | Standard Deviation 1702.25 |
Secondary
Cmax (ng/mL)
Maximum post dose plasma drug concentration on \[Cmax (ng/mL)\] Days 1 and 2
Time frame: Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose.
Population: Day 1 data only available for 7 subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ANA001 | Cmax (ng/mL) | Day 1: Cmax (ng/mL) | 348.06 ng/mL | Standard Deviation 212.343 |
| ANA001 | Cmax (ng/mL) | Day 2: Cmax (ng/mL) | 435.91 ng/mL | Standard Deviation 204.059 |
Secondary
Median Time to 2-point Improvement WHO Clinical Improvement Scale
Median Time to 2-point Improvement in WHO Ordinal Scale for Clinical Improvement. This is a 9 point ordinal scale with 0 indicating No clinical or virological evidence of infection and 8 indicating Death
Time frame: Randomization to Day 60
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ANA001 | Median Time to 2-point Improvement WHO Clinical Improvement Scale | 4.15 Days |
| Matching Placebo | Median Time to 2-point Improvement WHO Clinical Improvement Scale | 13.91 Days |
Secondary
Median Time to Hospital Discharge
Median time until patient is discharged from hospital. Discharge is defined as a score of 1 or 2 in the WHO Ordinal Scale for Clinical Improvement. This is a 9 point ordinal scale with 0 indicating No clinical or virological evidence of infection and 8 indicating Death.
Time frame: Randomization to Day 60
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ANA001 | Median Time to Hospital Discharge | 6.03 Days |
| Matching Placebo | Median Time to Hospital Discharge | 13.92 Days |
Secondary
Median Time to Resolution of COVID-19 Symptoms
Median time (in days) to resolution of subjective symptoms assessed by the Investigator to be potentially due to COVID-19 including: fever, cough (productive or non-productive), sore throat, malaise, headache, muscle pain, gastrointestinal symptoms (i.e., nausea, vomiting, or diarrhea), shortness of breath (with or without exertion), and respiratory distress
Time frame: Randomization to Day 60
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ANA001 | Median Time to Resolution of COVID-19 Symptoms | 17 Days |
| Matching Placebo | Median Time to Resolution of COVID-19 Symptoms | 16 Days |
Secondary
Median Time to Time-to-Viral Load Undetectable
Median number of days to viral load undetectable by nasopharyngeal (NP) swab
Time frame: Randomization to Day 60
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ANA001 | Median Time to Time-to-Viral Load Undetectable | 13.09 Days |
| Matching Placebo | Median Time to Time-to-Viral Load Undetectable | 13.1 Days |
Secondary
Tmax (h)
Time to maximum post dose plasma drug concentration on \[Tmax (h)\] Days 1 and 2
Time frame: Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose.
Population: Day 1 data only available for 7 subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ANA001 | Tmax (h) | Day 1: Tmax (h) | 4.884 (h) | Standard Deviation 2.3139 |
| ANA001 | Tmax (h) | Day 2: Tmax (h) | 3.983 (h) | Standard Deviation 2.4002 |