Back to resultsA Prospective, Phase II Study to Evaluate Safety of 101-PGC-005 ('005) for Moderate to Severe COVID-19 Disease Along With Standard of Care
Primary Purpose
COVID-19
Status
Terminated
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
101-PGC-005 ('005) + SOC
Placebo + SOC
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Glucocorticoids, Corticosteroids, Dexamethasone, Infectious disease, Cytokine storm
Eligibility Criteria
Inclusion Criteria:
- Patients willing and able to provide voluntary written informed consent and to follow the protocol specific requirements.
- Male or female patients over 18 years old.
- Patients with positive RT-PCR test for SARS-CoV-2 in nasopharyngeal or oropharyngeal swabs (sample collected within 7 days prior to enrollment) who are admitted or being admitted to the hospital for a primary diagnosis of COVID-19.
- In the case of female patients of child-bearing potential, a negative blood pregnancy test prior to beginning the therapy.
- Patients intended to be hospitalized to receive SOC including dexamethasone treatment for COVID-19.
Exclusion Criteria:
Exclusion Criteria:
- Patients with evidence of other serious infections.
- Malignancy.
Background disease which, in the opinion of the investigator prevents the patient from participating in the study such as:
- Presence of serious chronic infectious.
- A condition resulting in immunodeficiency.
- Participants with glucose levels upon admission ≥ 250 mg/dL
- Acute psychosis
- Patients in a critical stage of COVID-19 disease that require mechanical ventilation.
- Pregnant and lactating women.
- Patients that are currently or have participated in other clinical studies with investigational drug, biological agent, or device within 1 month or within 5 half-lives (of the drug/biologic) prior to enrollment (whichever is longer).
- Patient currently receiving chemotherapy or immunosuppressive agents not including dexamethasone within 30 days before the screening.
Sites / Locations
- The COVID-19 Unit, Rambam Health Care Campus
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
COVID-19 Patients
Control
Arm Description
Moderate to severe COVID-19 patients receiving SOC and '005.
Moderate to severe COVID-19 patients receiving SOC and placebo.
Outcomes
Primary Outcome Measures
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 2.
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 3.
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 4.
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 10.
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
Secondary Outcome Measures
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 2.
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 3.
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 4.
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 10.
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Evaluate incidence of Adverse Events/Serious Adverse Events (AEs/SAEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) thru the study.
The 28 days discharge rate.
Comparison of 28 days discharge rate.
COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged.
COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged .
COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged.
COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged .
Reduction in inflammatory blood markers.
Reduction in CRP, or Ferritin levels at days 10 and 28.
Reduction in inflammatory blood markers.
Reduction in CRP, or Ferritin levels at days 10 and 28.
Improvement of COVID-19 symptoms.
Improvement in 1 or more COVID-19 symptoms severity from baseline (temperature, rate PaO2/FiO2, Mechanical ventilation or not mechanical ventilation) at days 10 or 28.
Improvement of COVID-19 symptoms.
Improvement in 1 or more COVID-19 symptoms severity from baseline (temperature, rate PaO2/FiO2, Mechanical ventilation or not mechanical ventilation) at days 10 or 28.
Time to Saturation ≥94% on Room Air
Time to Saturation ≥94% on Room Air at day 10
Time to Saturation ≥94% on Room Air
Time to Saturation ≥94% on Room Air at day 28.
Blood evaluation for '005 PK.
Evaluation of '005 kinetics in the blood at Day 1: at baseline 30 min, 1, 2, 4, 5, 6, 8 and 24hr post dose
Blood evaluation for '005 PK.
Evaluation of '005 kinetics in the blood at Day 3: at baseline 30 min, 1, 2, 4, 5, 6, 8 and 24hr post dose
Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes.
Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes at Day 4 and 10.
Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes.
Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes at Day 4 and 10.
Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms
Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms at Day 4.
Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms
Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms at Day 10.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05195749
Brief Title
A Prospective, Phase II Study to Evaluate Safety of 101-PGC-005 ('005) for Moderate to Severe COVID-19 Disease Along With Standard of Care
Official Title
A Prospective, Phase II Study to Evaluate Safety of 101-PGC-005 ('005) for Moderate to Severe COVID-19 Disease Along With Standard of Care
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
Low Enrollment
Study Start Date
January 13, 2022 (Actual)
Primary Completion Date
February 14, 2023 (Actual)
Study Completion Date
February 14, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
101 Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
In December 2019, a novel pneumonia caused by a previously unknown pathogen emerged in Wuhan, China. The pathogen was soon identified as a novel coronavirus (SARS-CoV-2), which is closely related to severe acute respiratory syndrome CoV (SARS-CoV) COVID-19, caused by the SARS-CoV-2 virus, leading to a major global public health threat. Many COVID-19 patients develop acute respiratory distress syndrome (ARDS) leading to death. The recent RECOVERY Trial demonstrated the success of dexamethasone in treating late-stage COVID-19 patients. However, use of dexamethasone increases mortality in the early stage of the disease, and dexamethasone is further limited because the therapeutic dose and duration is insufficient to safely and effectively treat most COVID-19 patients. As the majority of cells have glucocorticoid receptors to which dexamethasone binds, highly toxic doses would be needed to effectively treat COVID-19, which results in increased mortality as well as decreased natural immunity (via T-cell and other immune cell modulation). The investigational product 101-PGC-005 ('005) - a prodrug of dexamethasone that is targeted to only activated macrophages - will address the many safety and efficacy issues that limit dexamethasone. '005 can achieve much higher anti-inflammatory doses and avoid all undesirable immunosuppressive activities caused by standard dexamethasone administration, resulting in an even greater reduction in mortality among hospitalized patients and significantly reducing long term morbidity in patients who survive.
Detailed Description
This prospective Phase IIa study will evaluate the safety of '005 for moderate to severe COVID-19 disease along with Standard of Care (SOC) treatment. The Nineteen (19) eligible patients will be enrolled to receive '005 + SOC, 10 additional patients will be enrolled to a control group receiving the SOC together with placebo.
At the first open-label stage, 3+3+3 design will be implemented. Three (3) patients will be enrolled to receive 10mg '005 together with SOC, three (3) patients will receive 20mg'005 together with SOC, and three (3) patients will receive 30mg '005 together with SOC if no safety concerns are identified the second stage will be initiated.
At the second double blind stage neither the participants nor the investigator will know which treatment participants are receiving until the clinical trial is over [20 patients will be enrolled and randomly allocated in a 1:1 ratio to the treatment (SOC +'005) or placebo group (SOC + placebo)]. The treatment dose will be chosen based on the first stage safety results.
NOTE: '005 will be administered daily for three (3) consecutive days starting from the day of enrollment.
Standard of Care will be administered as long as required, per Investigator's judgment, institutional practice, or local, national, or international guidelines for COVID-19 management.
A screening period of up to 7 days (Day-7 to Day-1) prior to enrollment will be followed by a study period of 28 days. Patients will be administered '005 daily from Day-1 to Day 3.
Total duration of study participation will not exceed 35 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Glucocorticoids, Corticosteroids, Dexamethasone, Infectious disease, Cytokine storm
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
19 eligible patients will be enrolled to receive '005 + Standard of Care (SOC) and 10 patients will be enrolled to a control group receiving the SOC + placebo. The 1st open-label stage a 3+3+3 design will be implemented. 3 patients will receive 10mg '005 + SOC, 3 patients will receive 20mg '005 + SOC, and 3 patients will receive 30mg '005 + SOC. If no safety concerns are identified the 2nd stage will be initiated. All dose-escalation decisions will be based on previous cohort safety data, and doses will not be escalated unless 2 patients receiving the highest current dose have been observed for 24 hours post the 3rd dose. At the 2nd double blind stage neither the participants nor the investigator will know which treatment participants are receiving until the clinical trial is over. 20 patients will be enrolled and randomly allocated in a 1:1 ratio to the treatment (SOC + '005) or placebo group (SOC + placebo). The treatment dose will be chosen based on the 1st stage safety results.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blind, neither the participants nor the investigator is aware of the assigned treatment.
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
COVID-19 Patients
Arm Type
Experimental
Arm Description
Moderate to severe COVID-19 patients receiving SOC and '005.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Moderate to severe COVID-19 patients receiving SOC and placebo.
Intervention Type
Drug
Intervention Name(s)
101-PGC-005 ('005) + SOC
Intervention Description
Three consecutive days of '005 administration
Intervention Type
Drug
Intervention Name(s)
Placebo + SOC
Intervention Description
Three consecutive days of placebo administration
Primary Outcome Measure Information:
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 2.
Description
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
Time Frame
At day 2
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 3.
Description
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
Time Frame
At day 3
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 4.
Description
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
Time Frame
At day 4
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 10.
Description
Evaluate the incidence of steroid-induced hyperglycemia Fasting Plasma Glucose (FPG).
Time Frame
At day 10
Secondary Outcome Measure Information:
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 2.
Description
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
Time Frame
At day 2
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 3.
Description
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
Time Frame
At day 3
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 4.
Description
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
Time Frame
At day 4
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 10.
Description
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
Time Frame
At day 10
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Description
Evaluate the incidence of vital signs abnormality (i.e., pulse, oxygen saturation and blood pressure).
Time Frame
At day 28
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Description
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
Time Frame
At day 2
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Description
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
Time Frame
At day 3
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Description
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
Time Frame
At day 4
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Description
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
Time Frame
At day 10
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Description
Evaluate the incidence of clinically significant changes in the blood CBC, and biochemistry.
Time Frame
At day 28
Title
To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.
Description
Evaluate incidence of Adverse Events/Serious Adverse Events (AEs/SAEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) thru the study.
Time Frame
At 28 days
Title
The 28 days discharge rate.
Description
Comparison of 28 days discharge rate.
Time Frame
At 28 days
Title
COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged.
Description
COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged .
Time Frame
At 10 days
Title
COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged.
Description
COVID-19 severity improvement by MOH COVID-19 severity scale while in hospital, and at days 10 and 28 if discharged .
Time Frame
At 28 days
Title
Reduction in inflammatory blood markers.
Description
Reduction in CRP, or Ferritin levels at days 10 and 28.
Time Frame
At 10 days
Title
Reduction in inflammatory blood markers.
Description
Reduction in CRP, or Ferritin levels at days 10 and 28.
Time Frame
At 28 days
Title
Improvement of COVID-19 symptoms.
Description
Improvement in 1 or more COVID-19 symptoms severity from baseline (temperature, rate PaO2/FiO2, Mechanical ventilation or not mechanical ventilation) at days 10 or 28.
Time Frame
At day 28
Title
Improvement of COVID-19 symptoms.
Description
Improvement in 1 or more COVID-19 symptoms severity from baseline (temperature, rate PaO2/FiO2, Mechanical ventilation or not mechanical ventilation) at days 10 or 28.
Time Frame
At day 10
Title
Time to Saturation ≥94% on Room Air
Description
Time to Saturation ≥94% on Room Air at day 10
Time Frame
At day 10
Title
Time to Saturation ≥94% on Room Air
Description
Time to Saturation ≥94% on Room Air at day 28.
Time Frame
At day 28
Title
Blood evaluation for '005 PK.
Description
Evaluation of '005 kinetics in the blood at Day 1: at baseline 30 min, 1, 2, 4, 5, 6, 8 and 24hr post dose
Time Frame
At day 1: at baseline 30 min, 1, 2, 4, 5, 6, 8 and 24hr post dose
Title
Blood evaluation for '005 PK.
Description
Evaluation of '005 kinetics in the blood at Day 3: at baseline 30 min, 1, 2, 4, 5, 6, 8 and 24hr post dose
Time Frame
At day 3: at baseline 30 min, 1, 2, 4, 5, 6, 8 and 24hr post dose
Title
Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes.
Description
Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes at Day 4 and 10.
Time Frame
At day 4
Title
Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes.
Description
Changes from baseline in pro-inflammatory cytokines and Lymphocyte subtypes at Day 4 and 10.
Time Frame
At day 10
Title
Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms
Description
Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms at Day 4.
Time Frame
At day 4
Title
Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms
Description
Correlation with pro-inflammatory cytokines and change in COVID-19 symptoms at Day 10.
Time Frame
At day 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients willing and able to provide voluntary written informed consent and to follow the protocol specific requirements.
Male or female patients over 18 years old.
Patients with positive RT-PCR test for SARS-CoV-2 in nasopharyngeal or oropharyngeal swabs (sample collected within 7 days prior to enrollment) who are admitted or being admitted to the hospital for a primary diagnosis of COVID-19.
In the case of female patients of child-bearing potential, a negative blood pregnancy test prior to beginning the therapy.
Patients intended to be hospitalized to receive SOC including dexamethasone treatment for COVID-19.
Exclusion Criteria:
Exclusion Criteria:
Patients with evidence of other serious infections.
Malignancy.
Background disease which, in the opinion of the investigator prevents the patient from participating in the study such as:
Presence of serious chronic infectious.
A condition resulting in immunodeficiency.
Participants with glucose levels upon admission ≥ 250 mg/dL
Acute psychosis
Patients in a critical stage of COVID-19 disease that require mechanical ventilation.
Pregnant and lactating women.
Patients that are currently or have participated in other clinical studies with investigational drug, biological agent, or device within 1 month or within 5 half-lives (of the drug/biologic) prior to enrollment (whichever is longer).
Patient currently receiving chemotherapy or immunosuppressive agents not including dexamethasone within 30 days before the screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Khetam Hussein, MD
Organizational Affiliation
Rambam Healthcare Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
The COVID-19 Unit, Rambam Health Care Campus
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Prospective, Phase II Study to Evaluate Safety of 101-PGC-005 ('005) for Moderate to Severe COVID-19 Disease Along With Standard of Care
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