Study to Evaluate the Efficacy and Safety of EG009A Intramuscular Injection Plus Dexamethason
Scientific Title of Study
A Phase 2, Randomized, Double blind, Placebo-controlled, Two-arm Study to Evaluate the Efficacy and Safety of Hydroxyprogesterone Caproate Intramuscular Injection Plus Dexamethasone Compared to Dexamethasone Alone in Patients with Moderate COVID-19 disease (Non-intubated, Nonmechanical Ventilation).
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
HPC-EG-009A- 2.2 Version No. 2.0 dated 26/Jun/2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej, Ahmedabad, GUJARAT – 382210, India Ahmedabad Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Details of Contact Person Scientific Query
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej, Ahmedabad, GUJARAT – 382210, India Ahmedabad Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Details of Contact Person Public Query
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
Second Floor, Skoda House, Opposite L J Campus S G Highway, Sarkhej, Ahmedabad, GUJARAT – 382210, India Ahmedabad Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Source of Monetary or Material Support
Evergreen Therapeutics, Inc.
Address: Evergreen Therapeutics, Inc.
10411 Motor City Drive, Suite 500
Bethesda, MD 20817, USA
Primary Sponsor
Name
Evergreen Therapeutics Inc
Address
Evergreen Therapeutics, Inc.
10411 Motor City Drive, Suite 500
Bethesda, MD 20817, USA
Patients must meet all inclusion criteria to be eligible for study Participation.
1. Willing and able to provide written informed consent, or with alegal representative who can provide informed consent, or
enrolled under International Conference on Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator prior to performing study procedures
2. Male or female patients aged between 45 to 60 years, both
inclusive, with gender balance ensured through stratification upon randomization.
3. Patient has COVID-19 symptoms less than or equal to 10 days with moderate
severity including any of the following consistent with classification of moderate disease severity:
O2 saturation (SpO2) 90 percent to less than or equal to93 percent on room air or
Respiratory rate greater than or equal to 24 per min, breathlessness
4. Patients with score of 5 on WHO ordinal scale for clinical
improvement [non-invasive ventilation or high-flow oxygen]
Note: Patients admitted with immediate need for mechanical
ventilation are of a severity too critical for inclusion into this
protocol. Patients who are already in the hospital and have been removed from mechanical ventilation are not eligible.
5. Vaccination status for COVID-19 will not influence eligibility for the study.
6. Patient laboratory-confirmed COVID-19 infection as determined by PCR or other commercial or public health assay in any specimen, as documented by either of the following:
Patient has a SARS-CoV-2 PCR positive sample collected less than 72 hours prior to randomization
Patient has a SARS-CoV-2 PCR positive sample collected greater than or equal to72 hours prior to randomization, with a documented inability to obtain a repeat sample (e.g., due to lack of testing supplies, limited testing capacity, results taking greater than24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 pneumonia.
7. Patient understands and agrees to comply with planned study procedures.
8. Patient agrees to be placed on a prophylactic dose of
anticoagulation medication for prevention of deep venous
thrombosis (DVT) while hospitalized
9. Patients who are women of childbearing potential must have a negative pregnancy test
ExclusionCriteria
Details
Patients will not be eligible for study participation if they meet any of the exclusion criteria.
1. Patient has severe COVID-19 infection as per ICMR guideline
(Respiratory rate >30/min, breathlessness or SpO2 < 90% on
room air). Patients with WHO ordinal scale for clinical
improvement severity scores 6 or 7 at baseline will be excluded.
2. Patient is currently receiving extracorporeal membrane
oxygenation (ECMO), nitric oxide therapy, or high-frequency
oscillatory ventilation
3. Patient is unlikely to survive for > 24 hours from randomization, in the opinion of the investigator
4. Patient has a history of chronic oxygen use or any pre-existing respiratory condition that requires intermittent or continuous ambulatory oxygen prior to hospitalization
5. Patient has a history of venous thromboembolism (VTE), DVT, or pulmonary embolus
6. Patient has a malignancy of any type
7. Patient has breast cancer or a history of breast cancer and now cancer free for < 5 years
8. Patient has suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19)
9. Patients with any of following laboratory results out of the ranges detailed below at screening should be discussed depending on their medication:
Absolute neutrophil count less than or equal to 1.0 × 109/L
Platelets < 50 × 109/L
Alanine aminotransferase or aspartate aminotransferase > 5 × upper limit of normal
10. Patient is sharing a ventilator, or co-ventilating, with any other patient.
11. Patient has had treatment with immunomodulators or
immunosuppressant drugs, including but not limited to antiinterleukin (IL)-6, IL-6R, IL-1RA, IL-1 Beta within 7 days prior to randomization
12. Patient has history of long-term use of antirejection or
immunomodulatory drugs
13. Patient is pregnant or lactating
14. Patient has severe chronic kidney disease greater than or equal to Stage 4 or requiring dialysis
15. Patient has a known hypersensitivity to progesterone or DEX
16. Patient is taking systemic corticosteroids for an indication other than COVID-19
17. Patient has known or active human immunodeficiency virus
(HIV)/ acquired immune deficiency syndrome (AIDS) infection
18. Patient has known or active tuberculosis (TB) infection or evidence of latent TB
19. Patient has known or active hepatitis B or hepatitis C
20. History or presence of conditions that may place the patient at increased risk as determined by the investigator.
21. Has taken other investigational drugs or participated in any
clinical study within 30 days or 5 half-lives (if known) of the
investigational drug’s PK, PD, or biological activity (if known),
whichever is longer, prior to first dose of study drug in this study or is currently participating in another clinical study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Efficacy Endpoint: Proportion of patients showing 2 points improvement as per
WHO ordinal scale and mortality after 14 days of treatment.
Safety Endpoints:
Incidence of new bacterial, fungal, or opportunistic infection
Incidence of Grade 4 neutropenia (absolute neutrophil count [ANC] less than 500 per mm3)
Incidence of Grade 3-4 adverse events ([AEs]; clinical orlaboratory)
Incidence of serious adverse events (SAEs)
Incidence of abnormal electrocardiograms (ECGs) requiring clinical action
Proportion of patients with shock defined by persistent hypotension (systolic blood pressure (SBP) less than 90 mmHg or diastolic blood pressure (DBP) less than 60 mmHg) despite volume resuscitation, requiring vasopressors to maintain MAP greater than or equal to 65 mmHg and serum lactate level greater than 2mmol per L.
PD Blood Collection on Day 01, 04, 08, 15, 29, 58.
Secondary Outcome
Outcome
TimePoints
Efficacy Endpoint:
Improvement after completion of treatment of Day 7, 10, 21 and
Day 28 (average individual change from baseline for COVID-19
WHO Ordinal Scale for Clinical Improvement)
Proportion of patients alive and without respiratory failure at Day 29 of treatment (after 28 days of treatment)
Mean vital signs summary score on Days 4, 8, 15, 22, and 29 (average individual change from baseline)
Days in hospital to discharge
PD Blood Collection on Day 01, 04, 08, 15, 29, 58.
Target Sample Size
Total Sample Size="44" Sample Size from India="44" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a
Phase 2, multi-site, randomized, double-blind, placebo controlled, two-arm
study to evaluate the efficacy and safety of EG009A IM injection in patients
hospitalized with moderate COVID 19 infection as per ICMR guideline (WHO
Ordinal Scale for Clinical improvement score of 5 [non-intubated and
non-mechanical ventilation]).
Patients with
moderate COVID-19 infection as per ICMR guidelines (WHO Ordinal Scale for
Clinical Improvement score of 5 [non intubated and not under mechanical
ventilation]) will be eligible to participate in the study.