A Phase 2b Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study, Evaluating Efficacy and Safety of Allocetra-OTS in Patients With Severe or Critical COVID-19 With Associated Acute Respiratory Distress Syndrome (ARDS)
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|ClinicalTrials.gov Identifier: NCT04922957|
Recruitment Status : Recruiting
First Posted : June 11, 2021
Last Update Posted : August 20, 2021
|Condition or disease||Intervention/treatment||Phase|
|Covid19||Drug: ALLOCETRA-OTS Other: Placebo||Phase 2|
This is a Phase 2b multi-center, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of intravenous (IV) Allocetra-OTS 10x10^9 cells vs placebo (1:1) in adult hospitalized patients with severe or critical Coronavirus Disease 2019 (COVID-19) with associated acute respiratory distress syndrome (ARDS).
Severe and critical COVID-19 are defined as follows:
Severe COVID-19: shortness of breath at rest, or respiratory distress, or respiratory rate (RR) ≥30 per minute, or SpO2 ≤93% on room air at sea level.
Critical COVID-19: respiratory failure, requiring at least one of the following: oxygen delivered by high-flow nasal cannula or noninvasive positive pressure ventilation.
After a patient has signed the informed consent form (ICF), and after confirmation that the patient meets all eligibility criteria, the patient will be enrolled in the study. The two subpopulations, severely ill and critically ill patients, will be randomized 1:1 into the active treatment and placebo groups via two separate randomizations schemes.
Study treatment (Investigational Product or placebo) administration will occur on Day 1 as close as possible to and no later than 48 hours from randomization. Assessments, performed on Day 1 prior to study treatment administration, will be considered as baseline assessments.
Patients will be followed for efficacy and safety through 6 months. Following study treatment administration, patients will be assessed daily for a period of 7 days. The next visits are planned to occur on Days 14, 28 and 60. A safety follow-up phone call will be scheduled to occur 6 months post study treatment. Hospitalized patients will be monitored on a daily basis until discharge or up to 60 days post study treatment administration.
Blood samples for safety assessment will be analyzed locally as per institutional guidelines.
Additional blood samples will be collected for potential exploratory analyses. Such biomarker analyses will be performed centrally as per Sponsor requirements.
Patients who drop out within the interval between the randomization and study treatment administration will be replaced to keep the originally planned sample size.
The trial will include periodic and ad-hoc Data Safety Monitoring Board (DSMB) review during the study period.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||152 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
152 patients will be allocated in a 1:1 ratio between the 2 cohorts:
|Masking:||Double (Participant, Investigator)|
|Masking Description:||Randomization will be in a double blinding fashion. The IP will be delivered with a cover to maintain blinding.|
|Official Title:||A Phase 2b Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study, Evaluating Efficacy and Safety of Allocetra-OTS in Patients With Severe or Critical COVID-19 With Associated Acute Respiratory Distress Syndrome (ARDS)|
|Estimated Study Start Date :||September 2021|
|Estimated Primary Completion Date :||June 2022|
|Estimated Study Completion Date :||December 2022|
Placebo Comparator: Placebo
Ringer's lactate solution
Ringer's lactate solution
Single IV dose of Allocetra-OTS containing 10x10^9 cells
The product contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension containing early apoptotic cells.
- Time (days) to improvement [ Time Frame: 28 days ]
The first day, during the period of 28 days post study treatment, when a patient reached the score of 6, 7 or 8 on the 8-point ordinal scale. If no improvement is reached by Day 28, the patient will be assigned a maximal score of 29.
The 8-point ordinal scale of the clinical severity status scores is as follows:
Death=1; Hospitalized, on IMV or ECMO=2; Hospitalized, on noninvasive ventilation or high-flow oxygen devices=3; Hospitalized, requiring supplemental oxygen by mask or nasal canula=4; Hospitalized, not requiring supplemental oxygen=5; Hospitalized, not requiring supplemental oxygen and not requiring ongoing inpatient medical care=6; Not hospitalized, limitations on activities=7; Not hospitalized, no limitations on activities=8.
- Support by IMV/ECMO [ Time Frame: 28 days ]If required during the period of 28 days post study treatment, a patient will be assigned the maximal score of 29.
- Mortality [ Time Frame: 28 days ]Mortality by Day 28 post study treatment administration. Deceased patients will be assigned the maximal score of 29.
- Time (days) to improvement, defined as the first day, during a period of 28 days and 60 days post study treatment administration, when the patient reached the score of 6, 7 or 8 on the 8-point ordinal scale. [ Time Frame: 60 days ]
- All-cause mortality during the period of 28 days and 60 days. [ Time Frame: 60 days ]
- Proportion of patients alive and free of respiratory failure, defined as need for IMV, ECMO, noninvasive ventilation, or high-flow nasal cannula oxygen delivery on Days 28 and 60. [ Time Frame: 60 days ]
- Cumulative number of vasopressor-free days during the period of 28 days and 60 days. [ Time Frame: 60 days ]
- Cumulative number of days in the hospital during the period of 28 days and 60 days. [ Time Frame: 60 days ]
- Cumulative number of days in the ICU or Intermediate Care Unit (IMU) during the period of 28 days and 60 days. [ Time Frame: 60 days ]
- Safety - Number and severity of adverse events (AEs) and serious adverse events (SAEs) throughout 60-day follow-up period [ Time Frame: 60 days ]
- Safety - Number and severity of AEs and SAEs throughout 180-day follow-up period [ Time Frame: 180 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04922957
|Contact: Odelia Ben Shitrit, MBAemail@example.com|
|Contact: Lior Binderfirstname.lastname@example.org|
|Hadassah Ein Kerem Medical Center||Recruiting|
|Contact: Rachel Kleinhaus 972-52-4347504 KlRachel@hadassah.org.il|
|Study Director:||Oren Hershkovitz, PhD||Enlivex Therapeutics R&D|