IRAK4 Inhibition in Treatment of COVID-19 With ARDS (I-RAMIC)

NCT04575610 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 2000028042
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the efficacy of PF-06650833 in addition to standard-of-care compared to standard-of-care treatment alone in improving outcomes in patients with COVID-19.

Conditions

COVID-19

Keywords

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (1)

• All-cause mortality at Day 29

  All-cause mortality at Day 29 (end of planned treatment period).

  Up to 29 days

Secondary Outcomes (24)

• Disease Severity (8 point scale)

  29 days

• Disease Severity (8 point scale)

  61 days

• Disease Severity (8 point scale)

  29 days

• Disease Severity (8 point scale)

  61 days

• Disease Severity (8 point scale)

  8 days

Study Arms (2)

PF-06650833 + Standard of Care

EXPERIMENTAL

Subjects randomized to the PF-06650833 arm of the study will receive 200 mg IR suspension formulation every 6 hours (via nasogastric \[NG\] tube, orogastric \[OG\] tube, or equivalent) if unable to take tablets by mouth (PO). All dosing of PF-06650833 will be in addition to current hospital SOC therapy.

Drug: PF-06650833

Placebo + Standard of Care

ACTIVE COMPARATOR

Matching placebo tablets will be administered.

Drug: Placebo

Interventions

PF-06650833 DRUG

Subjects randomized to the PF-06650833 arm of the study will receive 200 mg IR suspension formulation every 6 hours (via nasogastric \[NG\] tube, orogastric \[OG\] tube, or equivalent) if unable to take tablets by mouth (PO). Subjects for whom concomitant administration of a strong inhibitor of cytochrome P450 (CYP) 3A4 will have the dose of the IR formulation to 200 mg once daily (QD). Subjects who can take tablets PO will receive 400 mg PF-06650833 (2-200 mg tablets) of the MR formulation QD under fasted conditions (preferably at least 4 hours after and 1.5 hours before a meal). No dose adjustment is needed for subjects taking the MR tablet preparation, except if co-administered with ritonavir in which case the dose should be reduced to 200 mg MR QD. All dosing of PF-06650833 will be in addition to current hospital SOC therapy.

PF-06650833 + Standard of Care

Placebo DRUG

Matching placebo tablets will be administered.

Placebo + Standard of Care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male and female patients, including women of childbearing potential, at least 18 years of age, inclusive
• Participant (or legally authorized representative) capable of giving signed informed consent
• Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection
• Clinical findings and an imaging study consistent with ARDS;
• PaO2 / FiO2 ratio \< 300;
• A requirement for mechanical ventilation ≤ 48 hours prior to enrollment.
• Evidence of increased inflammation as assessed by hsCRP \> ULN AND at least ONE of the following being \> upper limit of normal (as available):
• ferritin
• procalcitonin
• D-dimer
• fibrinogen
• LDH
• PT/PTT

You may not qualify if:

• Suspected or known active systemic bacterial, viral (except SARS-CoV2 infection), or fungal infections
• Active herpes zoster infection
• Known active or latent tuberculosis (TB) or history of inadequately treated TB
• Active hepatitis B or hepatitis C
• Known history of human immunodeficiency virus (HIV) infection with a detectable viral load or CD4 count \< 500 cells / mm3 (patients for whom documented viral load or CD4 counts are available will be excluded)
• Active hematologic cancer
• Metastatic or intractable cancer
• Pre-existing neurodegenerative disease
• Severe hepatic impairment defined as Child-Pugh Class B or Class C at baseline
• Severe renal impairment with an estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73 m2
• Severe anemia (Hb \< 8.0 g/dL)
• Any of the following abnormal laboratory values:
• absolute lymphocyte count \<250 cells/mm3
• absolute neutrophil Count (ANC) \<1000 cells/mm3
• Platelet count \<50,000 cells/mm3

Sponsors & Collaborators

• Yale University: lead
• Pfizer: collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

1-(((2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methoxy)-7-methoxyisoquinoline-6-carboxamide

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

Study Officials

• Hyung Chun, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: October 5, 2020
• Study Start: November 27, 2020
• Primary Completion: October 6, 2021
• Study Completion: October 6, 2021
• Last Updated: October 26, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)