COVID-19
Conditions
Keywords
COVID-19, High Risk, Outpatient
Brief summary
The goal of this clinical trial is to evaluate the safety, tolerability, and efficacy of NP-101 in treating high-risk participants who have tested positive for Covid-19. The main question\[s\] it aims to answer are: * To evaluate the safety of NP-101, as well as establish the maximum tolerated dose in high risk Covid-19 positive patients. Participants will \[describe the main tasks participants will be asked to do, treatments they'll be given and use bullets if it is more than 2 items\]. If there is a comparison group: Researchers will compare \[insert groups\] to see if \[insert effects\].
Detailed description
This is a Phase IIa/IIb multicenter, interventional, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and efficacy of NP-101 in outpatient high-risk COVID-19 positive participants. Blinding roles: Participants, Investigators and Sponsor The study is comprised of two parts (Phase IIa and Phase IIb) and four cohorts. The first part of the trial (IIa) involves three cohorts and is a dose escalation study designed to select the maximum tolerated dose for use in the second part (IIb) of the study. In the dose escalation (Phase IIa) portion of the trial (n= 60), qualified participants will be enrolled in a parallel dose escalation design and randomized in a 3:1 \[active+best supportive care (BSC):placebo+BSC\]ratio to one of three cohorts of 20 participants each (15 active +BSC, 5 placebo + BSC). Cohort 1 (15 participants taking 600 mg capsules for a total daily dose of 3 grams of NP-101 plus BSC and 5 participants taking placebo plus BSC), and Cohort 2 (15 participants taking 600 mg capsules for a total daily dose of 4.8 g of NP-101+ BSC and 5 participants taking placebo plus BSC will run concurrently since acceptable safety data for the 3 g dose was obtained in an earlier phase II study. Cohort 1 will receive either 3 g Total Daily Dose (TDD) of NP-101 + BSC or Placebo+ BSC, Cohort 2 will receive either 4.8 g TDD of NP-101 +BSC or placebo + BSC) and Cohort 3 (15 participants taking 600 mg capsules for a total daily dose of 6 g of NP-101 + BSC and 5 participants taking placebo plus BSC.) Safety will be evaluated according to the terms of the Statistical Analysis Plan (SAP). In the second portion of the trial (Phase IIb), Participants enrolled in Cohort 4 (n= 248) will be randomized in a ratio of 1:1 (active+BSC : placebo+BSC) and will receive the Maximum Tolerated Daily Dose (MTDD) as determined by the parameters set by the SAP and approved by the pharmacovigilance team.
Interventions
DRUGNP-101
NP-101 is an organically derived, GMP manufactured product covered under IND #152687.
OTHERPlacebo
Identical placebo
Sponsors
Novatek Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Participant, Investigator will all be blinded.
Intervention model description
Phase IIb will be a 2 parallel arms, double - blind, randomized, placebo controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent form * A resting SpO2 of \>93% on room air. * Stated willingness to comply with all study procedures and availability for the duration of the study * Male or female, aged 18 and over, presenting with mild to moderate clinical symptoms of Covid- 19 infection (per FDA guidance - see appendix 3) with symptom onset within 5 days prior to the day of randomization * Positive COVID-19 infection confirmed by RT-PCR within the last 5 days of the day of randomization * A score of ≥ 2 (moderate) on a minimum of 1 symptom on the PRO Symptom Survey on the day of randomization * Ability to take oral medication and be willing to adhere to the dosing regimen (Twice a day - BID for 14 days) * For females of reproductive potential: negative pregnancy test at screening and use of highly effective contraception method during study participation and for an additional 4 weeks after the end of study drug administration * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional 4 weeks after the end of study drug administration * Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration * To be considered high risk, participants should have at least one of the following conditions: * age ≥60 years; * active cancer * chronic kidney disease; * chronic lung disease including COPD * Obesity (BMI ≥30) * serious heart conditions \[heart failure, coronary artery disease, or cardiomyopathies\]; * Diabetes (type 1 or type 2) * Immunocompromised state (weakened immune system or autoimmune diseases) * Chronic liver disease * Cystic fibrosis * HIV infection * Smoking, current or former * Sickle cell disease or thalassemia * Solid organ or blood stem cell transplant * Stroke or cerebrovascular disease
Exclusion criteria
* Current or recent (within 4 weeks) treatment with any corticosteroids; however, inhaled steroids, which are used to treat acute or chronic bronchial inflammation, will be permitted * Severe Covid-19 symptoms (severe per FDA classification - see appendix 3) * Requires immediate admission to hospital for any reason * Pregnancy or lactation * Known allergic reactions to components of black seed oil or thymoquinone * Treatment with another investigational drug or other investigational intervention within 2 weeks of study start and throughout study duration. * Significant hepatic disease (ALT/AST\> 4 times the ULN); any laboratory parameter \>/= 4 times the ULN or platelet count \<100,000/µ L or neutrophilic granulocyte absolute count o \<500/mm3 * History of moderate to severe CKD, (i.e. on hemodialysis or has an estimated glomerular filtration rate less than 45mL/min) at the time of enrollment * Participants with inflammatory bowel disease (such as Crohn's) that could affect the intestinal absorption of NP-101 enteric coated capsules. * Known uncontrolled HIV (with a recent viral load \> 50 copies/mL or CD4\<200 cells/mm3 or known active uncontrolled Hepatitis B (defined as HBsAg-positive or detectable HBV DNA viral load) or known active Hepatitis C (defined as detectable HCV RNA viral load) infection * Influenza diagnosis (confirmed by testing) during screening or within prior 14 days * Any uncontrolled condition(s) or diagnosis, both physical or psychological, or physical exam finding that precludes participation, as per investigator * Current treatment with CYP2C9 substrates (see Appendix 5)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Establishment of MTDD | Fourteen days per dose (Phase IIA Only) | Number of DLTS (Dose Limiting Toxicities) in the NP-101 arm at each dose compared to placebo and the safety threshold. This outcome measure ONLY APPLIES TO the Phase-IIa (Dose-finding) component of the trial. |
| Safety and Tolerability of NP-101 vs Placebo (Phase IIa and IIb) | Through Day 45 | Evaluation of the number of overall adverse events, related adverse reactions, adverse events leading to discontinuation of study drug, hospitalization, or death. |
| Time to Sustained Clinical Recovery | Through Day 5 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. This outcome measure is defined as the difference of Sustained Clinical Recovery (SCR) rates on Day 5 in patients taking the MTDD of NP-101 vs Placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference of Change in Log2 of Viral Load From Baseline to Day-7 Between NP-101 and Placebo | Enrollment to Day-7 on study | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. With this outcome measure, we aim to compare the change in viral load and cycle threshold profiles from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. As Viral Load and Cycle Threshold values were not available on Day-14 as the RT-PCR assessment of Covid-19 was negative, we are able to provide the change only from Baseline to Day-7. |
| Difference of Change in ORF1 Gene From Baseline to Day-7 Between NP-101 and Placebo | Enrollment to Day-7 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. With this outcome measure, we aim to compare the change in viral load and cycle threshold profiles from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. As Viral Load and Cycle Threshold values were not available on Day-14 as the RT-PCR assessment of Covid-19 was negative, we are able to provide the change only from Baseline to Day-7 |
| Difference in Change of E-Gene From Baseline to Day-7 Between N101 and Placebo | From Enrollment to Day-7 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. With this outcome measure, we aim to compare the change in viral load and cycle threshold profiles from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. As Viral Load and Cycle Threshold values were not available on Day-14 as the RT-PCR assessment of Covid-19 was negative, we are able to provide the change only from Baseline to Day-7. |
| Differenc in Change of N-Gene From Baseline to Day-7 Between NP-101 and Placebo | From enrollment to Day-7 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. . With this outcome measure, we aim to compare the change in viral load and cycle threshold profiles from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. As Viral Load and Cycle Threshold values were not available on Day-14 as the RT-PCR assessment of Covid-19 was negative, we are able to provide the change only from Baseline to Day-7. |
| RT-PCR Negative/Undetectable Rate at Day 7 | Days 0 to 7 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the percentage of RT-PCR negative/undetectable (i.e., viral clearance) on Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo |
| RT-PCR Negative/Undetectable on Day-14 | Day 0 to Day-14 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the percentage of RT-PCR negative/undetectable (i.e., viral clearance) on Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo |
| Median Time to Sustained Clinical Recovery | From Day-0 to Day-28 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this aim, we compare the median days from randomization to the attainment of Sustained Clinical Recovery between NP-101 and Placebo arms |
| Median Day to Complete Clinical Recovery | From Day-0 to Day-28 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this aim, we compare the median days from randomization to the attainment of Sustained Clinical Recovery between NP-101 and Placebo arms |
| Median Days to Complete Clinical Resolution | From Day-0 to Day-28 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this aim, we compare the median days from randomization to the attainment of the complete clinical resolution between NP-101 and Placebo. |
| Difference of the Change From Randomization to Day-7 of Absolute Counts of CD4+ and CD8+ Markers Between NP-101 and Placebo Arms. | From Day-0 to Day-7 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the change in effector immune cells, specifically CD4+ and CD8+ T lymphocytes, from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. We have a total of 36 markers for CD4+ and CD8+ Flow cytometry markers are combinations of the following immune cell types having various immune responses singly or in combination: CD3, CD5, CD8, CD16, CD19, CD45, CCR7, and CXCR3. The flow-cytomerty markers include the immune cell types: CD3, CD4, CD8, CD16, CD19, CD45, CCR7, and CXCR3. Markers are absolute counts of cells per cubic milimeter. |
| Difference of the Change From Randomization to Day-7 ın the Ratio of the Absolute Counts of CD4+ and CD8+ Markers Between NP-101 and Placebo Arms. | From Day-0 to Day-7 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the change in the ratio of CD4+ and CD8+ T lymphocytes, from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. Both CD4+ and CD8+ are measured as absolute counts of cells per cubic milimeter. |
| Difference of the Change From Randomization to Day-7 of Percentages of CD4+ and CD8+ Markers Between NP-101 and Placebo Arms. | From Day-0 to Day-7 Cell Percentages | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the change in effector immune cells, specifically CD4+ and CD8+ T lymphocytes, from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. We have a total of 36 markers for CD4+ and CD8+ Flow cytometry markers are combinations of the following immune cell types having various immune responses singly or in combination: CD3, CD5, CD8, CD16, CD19, CD45, CCR7, and CXCR3. The flow-cytomerty markers include the immune cell types: CD3, CD4, CD8, CD16, CD19, CD45, CCR7, and CXCR3. These marker entries represent the percentages of the combination of these immune cell types or their percentages in the biological sample. |
| Difference of the Change From Randomization to Day-14 of Absolute Counts of CD4+ and CD8+ Markers Between NP-101 and Placebo Arms. | From Day*0 to Day-14 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the change in effector immune cells, specifically CD4+ and CD8+ T lymphocytes, from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. We have a total of 36 markers for CD4+ and CD8+. Flow cytometry markers are combinations of the following immune cell types having various immune responses singly or in combination: CD3, CD5, CD8, CD16, CD19, CD45, CCR7, and CXCR3. The flow-cytomerty markers include the immune cell types: CD3, CD4, CD8, CD16, CD19, CD45, CCR7, and CXCR3. Markers are absolute count of cells per cubic milimeter. |
| Difference of the Change From Randomization to Day-14 ın the Ratio of the Absolute Counts of CD4+ and CD8+ Markers Between NP-101 and Placebo Arms. | From Day-0 to Day-14 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the change in the ratio of CD4+ and CD8+ T lymphocytes, from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. Both CD4+ and CD8+ are measured as absolute counts of cells per cubic milimeter. |
| Difference of the Change From Randomization to Day-14 of Percentages of CD4+ and CD8+ Markers Between NP-101 and Placebo Arms. | From Day-0 to Day-14 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the change in effector immune cells, specifically CD4+ and CD8+ T lymphocytes, from Randomization to Day 7 and Day 14 in participants taking the MED of NP-101 as compared to placebo. We have a total of 36 markers for CD4+ and CD8+. Flow cytometry markers are combinations of the following immune cell types having various immune responses singly or in combination: CD3, CD5, CD8, CD16, CD19, CD45, CCR7, and CXCR3. The flow-cytomerty markers include the immune cell types: CD3, CD4, CD8, CD16, CD19, CD45, CCR7, and CXCR3. These Markers represent the percentages of the combination of these immune cell types or their percentages in the biological sample. |
| Proportion of Participants With Symptom Progression | From Day-0 to Day28 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the rate of disease progression measured by the worsening by the Covid-19 symptoms from 'none' or 'mild' to 'moderate' or 'severe' and remaining at that level for at least two days before alleviation or resolution, or the experience of hospitalization or death due to Covid-19 symptom worsening in participants taking the MED of NP-101 versus placebo |
| Proportion of Paticipants With Long-Covid Symptoms | Day-29 to Day-45 | This outcome measure ONLY APPLIES TO the Phase-IIb (efficacy) component of the trial per protocol. Therefore, the six arms of the Phase-IIa (dose-finding phase, three dose levels of NP-101 and placebo investigated) were not part of this data entry. In this objective, we aim to compare the rate of Long- Covid symptoms in participants taking the MED of NP-101 versus placebo. A patient will be classified as having experienced symptoms indicative of Long- Covid if they reported any new or ongoing mild, moderate, or severe Long- Covid symptoms captured on the daily symptom questionnaire, on any of the following days: Day 30 ± 2 days, Day 37 ± 2 days, or Day 45 ± 2 days |
Countries
United States
Contacts
STUDY_DIRECTORAhmed Kaseb, MD
Novatek Pharmaceuticals
Participant flow
Recruitment details
60 participants were enrolled during the Phase-IIa component of the trial during which we identified the Phase-IIb dose. The remaining 110 participants were enrolled on the study during the Phase-IIb component.
Pre-assignment details
Participant eligibility was checked at the time of screening. If the date of randomization is not the same day of screening, the eligibility was checked again before randomization.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41.05 Year STANDARD_DEVIATION 7.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 45 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 5 | 0 / 15 | 0 / 5 | 0 / 15 | 0 / 5 | 0 / 50 | 0 / 60 |
| other Total, other adverse events | 4 / 15 | 3 / 5 | 6 / 15 | 3 / 5 | 12 / 15 | 4 / 5 | 12 / 50 | 21 / 60 |
| serious Total, serious adverse events | 0 / 15 | 0 / 5 | 0 / 15 | 0 / 5 | 0 / 15 | 0 / 5 | 0 / 50 | 0 / 60 |
Outcome results
None listed