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

NCT05195749 | Terminated Phase 2

• 1 other identifier: PGC-005-CP-101
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Keywords

Glucocorticoids; Corticosteroids; Dexamethasone; Infectious disease; Cytokine storm

Outcome Measures

Primary Outcomes (4)

• 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).

  At day 2

• 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).

  At day 3

• 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).

  At day 4

• 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).

  At day 10

Secondary Outcomes (26)

• To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 2.

  At day 2

• To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 3.

  At day 3

• To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 4.

  At day 4

• To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment at day 10.

  At day 10

• To assess the safety of '005 in moderate to severe COVID-19 patients with Standard of Care treatment.

  At day 28

Study Arms (2)

COVID-19 Patients

EXPERIMENTAL

Moderate to severe COVID-19 patients receiving SOC and '005.

Drug: 101-PGC-005 ('005) + SOC

Control

PLACEBO COMPARATOR

Moderate to severe COVID-19 patients receiving SOC and placebo.

Drug: Placebo + SOC

Interventions

101-PGC-005 ('005) + SOC DRUG

Three consecutive days of '005 administration

COVID-19 Patients

Placebo + SOC DRUG

Three consecutive days of placebo administration

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• 101 Therapeutics: lead

Study Sites (1)

The COVID-19 Unit, Rambam Health Care Campus

Haifa, 3109601, Israel

Location

MeSH Terms

Conditions

COVID-19; Communicable Diseases; Cytokine Release Syndrome

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation; Shock

Study Officials

• Khetam Hussein, MD

  Rambam Healthcare Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind, neither the participants nor the investigator is aware of the assigned treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: January 19, 2022
• Study Start: January 13, 2022
• Primary Completion: February 14, 2023
• Study Completion: February 14, 2023
• Last Updated: February 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)