Study in Healthy Subjects and Symptomatic Covid-19 Positive Patients to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of the Novel Self-administered Intranasal CG- SpikeDown Antiviral Drug
Study Details
Study Description
Brief Summary
This is a phase 1/2, randomized, placebo-controlled, double-blinded study, to assess safety of Caregen Intranasal CG-SpikeDown in healthy subjects and and safety and efficacy (via viral load profile) in non-hospitalized symptomatic COVID-19 patients within 3 days of symptoms onset.
All randomized COVID-19 patients will receive active drug or placebo in addition to standard of care treatment. Patients randomized to the DP active treatment will receive CG-SpikeDown intranasally once daily for seven days at either low (25 mg) or planned (50 mg) dose. The treatment period in this study, during both study stages, is 7 days.
The study will be divided into 2 stages:
Stage I will be conducted on 10 healthy subjects. In Stage II will include 60 symptomatic non-hospitalized COVID-19 patients and will be conducted at patients' homes during their self-isolation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is a phase 1/2, randomized, placebo-controlled, double-blinded study, which will assess safety and signs of efficacy (via viral load profile) of Caregen CG-SpikeDown drug self-administered IN, for symptomatic COVID-19 patients within up to 7 days of symptoms onset.
The study will be conducted in two stages. The first 2 patients in this stage will receive the vehicle treatment and will not undergo the first 24 hour hospitalization. The 3rd and 4th patients will receive a lower dose of 12.5 mg of the DP once daily for 7 days, and the first 24 hours will be hospitalized for the first 24 hours. The 5th patient will receive the 25 mg from the DP once daily for 7 days and will be hospitalized for the first 24 hours. The next 2 patients will receive the 25 mg dose and will not undergo the first 24 hour hospitalization. The next 3 patients will receive the optimal dose of 50 mg and will not undergo the first 24 hour hospitalization.
Subjects will be recruited to the study via study advertisement on social media and the subjects will be adequately compensated. The DP will be self-administered IN once daily for seven days. PK will be evaluated during Stage I at several timepoints during Day 1 and Day 6 of treatment. Toxicity will be evaluated during the entire study period during Stage I.
Stage II will include 60 symptomatic non-hospitalized COVID-19 patients and will be conducted at patients' homes during their self-isolation. The main objective of this stage is to further evaluate the safety profile of the DP, and to estimate the viral load kinetic and viral cycle threshold of the treated subjects. Patients will be enrolled to Stage II within 1-3 days of symptoms onset. All eligible patients will be randomized in a 1:1:1 ratio to one of the three study arms: Vehicle + SOC, low DP dose (25 mg) + SOC and the planned DP dose (50 mg) + SOC once daily intranasally for seven days.
The screening visit will be conducted remotely during this stage. If the patient does not have a positive COVID-19 diagnostic PCR test result from 72 hours prior to screening visit, the nurse will test the patient for COVID-19 in the patients' home with the rest of the study assessments for this visit.
Nasal swabs will be collected twice daily during Stage II. The first swab on each day will be collected by the nurse and the second one will be collected by the patient. Collection, handling and testing of the specimens will be done in accordance with the IFU of the diagnostic test.
Key Covid-19 symptoms will be collected on the first day of treatment, on the last day of treatment, and on follow-up Day 14 during Stage II. The key Covid-19 symptoms will be assessed using the NIAID Ordinal Scale.
It should be noted that according to Israeli policy, those who have tested positive for Covid-19 are required to stay in self-isolation at their homes. Following the FDA recommendation , in-person data collection will be limited to a single visit per day. The second nasal swab on each day will be done by patients themselves and collected by the study personnel during the next daily visit At day 14 and 30 post randomization, patients will be followed up via phone call, after which the study will be complete.
Safety review by the DSMB will occur following treatment of 30 patients with CG-SpikeDown. In addition, the DSMB will convene on a weekly basis to evaluate both safety and efficacy results.
The study will be conducted in up to 2 sites in Israel and include healthy subjects and non-hospitalized symptomatic COVID-19 patients. It is anticipated that the SOC procedures will be very similar for all patients. For this reason, the randomization will be centralized and not stratified by site.
Stage I of the study will not be randomized. The first 2 patients will receive the vehicle treatment, the next 2 patients will receive a lower dose of 12.5 mg and the next 3 patients will receive 25 mg and the final 3 patients will receive the optimal dose of 50 mg.
In Stage II, all eligible patients will be randomized in a 1:1:1 ratio to one of the three study arms: Vehicle + SOC, low DP dose (25 mg) + SOC and the planned DP dose (50 mg) + SOC.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: stage I- Healty The first 2 patients in this stage will receive the vehicle treatment and will not undergo the first 24 hour hospitalization. The 3rd and 4th patients will receive a lower dose of 12.5 mg of the DP once daily for 7 days, and the first 24 hours will be hospitalized for the first 24 hours. The 5th patient will receive the 25 mg from the DP once daily for 7 days and will be hospitalized for the first 24 hours. The next 2 patients will receive the 25 mg dose and will not undergo the first 24 hour hospitalization. The next 3 patients will receive the optimal dose of 50 mg and will not undergo the first 24 hour hospitalization |
Drug: CG-SpikeDown, intranasal formulation
The CG-SpikeDown peptide produces a dose-dependent increase in binding to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and a dose-dependent inhibition of SARS-CoV-2 protein binding to ACE2, the key cellular target. A similar inhibition of binding to ACE2 in human alveolar basal epithelial cells has been demonstrated.
|
| Active Comparator: Stage II- Placebo + SOC This arm will be include 20 This arm will be include 20 symptomatic non-hospitalized COVID-19 patients and will be conducted at patients' homes during their self-isolation, and they will be received Placebo + standard of care |
Drug: Vehicle (Placebo)
patients will receive active drug or placebo in addition to standard of care
Drug: Standard of core (type of therapy is depend of decide of the site)
patients will receive active drug or placebo in addition to standard of care
|
| Active Comparator: Stage II- DP low dose (25 mg) + SOC This arm will be include 20 symptomatic non-hospitalized COVID-19 patients and will be conducted at patients' homes during their self-isolation, and they will be received Drug product low does(25 mg) + standard of care |
Drug: CG-SpikeDown, intranasal formulation
The CG-SpikeDown peptide produces a dose-dependent increase in binding to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and a dose-dependent inhibition of SARS-CoV-2 protein binding to ACE2, the key cellular target. A similar inhibition of binding to ACE2 in human alveolar basal epithelial cells has been demonstrated.
Drug: Vehicle (Placebo)
patients will receive active drug or placebo in addition to standard of care
Drug: Standard of core (type of therapy is depend of decide of the site)
patients will receive active drug or placebo in addition to standard of care
|
| Active Comparator: Stage II- DP planned dose (50 mg) + SOC This arm will be include 20 This arm will be include 20 symptomatic non-hospitalized COVID-19 patients and will be conducted at patients' homes during their self-isolation, and they will be received Drug product planned does(50 mg) + standard of care |
Drug: CG-SpikeDown, intranasal formulation
The CG-SpikeDown peptide produces a dose-dependent increase in binding to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and a dose-dependent inhibition of SARS-CoV-2 protein binding to ACE2, the key cellular target. A similar inhibition of binding to ACE2 in human alveolar basal epithelial cells has been demonstrated.
Drug: Vehicle (Placebo)
patients will receive active drug or placebo in addition to standard of care
Drug: Standard of core (type of therapy is depend of decide of the site)
patients will receive active drug or placebo in addition to standard of care
|
Outcome Measures
Primary Outcome Measures
- SARS Cov-2 RT-PCR test [7 days]
Viral load is estimated from nasopharyngeal swabs and instructions for use is based on the package insert of the diagnostic. This assessment will be used to diagnose COVID-19 patients during Stage II in case they do not have a positive COVID-19 test result from 72 hours before the Stage II screening visit, and will also be used to assess viral load in COVID-19 patients during Stage II.
- Area under the plasma concentration versus time curve [7 days]
The following PK parameters evaluation collected 10 minutes prior to DP self-administration, immediately following DP self-administration, and 1, 2, 4 and 6 hours following DP self-administration, on Day 1 and Day 6 of treatment. These measurements will be collected only during Stage I (from 10 healthy subjects)
Secondary Outcome Measures
- NIAID ordinal scale [14 days]
Time to sustained clinical recovery. Sustained clinical recovery will be defined based on self-reported key COVID-19 related symptoms using the NIAID ordinal scale. • Clinical status on Day 7 and Day 14 assessed on the NIAID 8-point ordinal scale consisting of the following categories: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities and/or requiring home oxygen; Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, requiring supplemental oxygen; Hospitalized, on noninvasive ventilation or high-flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; and Death Maximum is 1. Not hospitalized, no limitations on activities; Minimum is 8. Death
- Peak Plasma Concentration [7 days]
The following PK parameters evaluation collected 10 minutes prior to DP self-administration, immediately following DP self-administration, and 1, 2, 4 and 6 hours following DP self-administration, on Day 1 and Day 6 of treatment. These measurements will be collected only during Stage I (from 10 healthy subjects)
Other Outcome Measures
- Time to maximum plasma concentration [7 days]
The following PK parameters evaluation collected 10 minutes prior to DP self-administration, immediately following DP self-administration, and 1, 2, 4 and 6 hours following DP self-administration, on Day 1 and Day 6 of treatment. These measurements will be collected only during Stage I (from 10 healthy subjects)
Eligibility Criteria
Criteria
Stage I Inclusion Criteria
-
Age ≥ 18 years in healthy condition
-
Able and willing to sign ICF
Stage I Exclusion Criteria
-
Known hypersensitivity to any of the DP ingredients.
-
Pregnant or lactating woman.
-
Participation in another clinical study within 4 weeks from screening
-
Patient has a positive test for HBV, HCV or HIV
-
Subjects diagnosed with allergic rhinitis and/or deviated septum and/or sinusitis.
-
Any medical condition that in the investigator's opinion will jeopardize the patient's ability to follow the protocol.
Stage II Inclusion Criteria
-
Age ≥ 18 years
-
Laboratory confirmed SARS-CoV2 Infection by nasopharyngeal RT-PCR.
-
COVID-19 symptoms within 3 days of symptoms onset
-
Patients diagnosed with COVID-19 that are not hospitalized (classified on the NIAID 8-point ordinal scale as 1 or 2).
Stage II Exclusion Criteria
-
Patients who may require hospitalization during the study
-
Immunocompromised COVID-19 patients.
-
Known hypersensitivity to any of the DP ingredients.
-
Patient has a positive test for HBV, HCV or HIV
-
Pregnant or lactating woman.
-
Participation in another clinical study within 4 weeks from screening
-
Subjects diagnosed with allergic rhinitis and/or deviated septum and/or sinusitis.
-
Any medical condition that in the investigator's opinion will jeopardize the patient's ability to follow the protocol.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Caregen Co. Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CG-S-01