NCT04933799

Brief Summary

The aim of the current clinical study is to evaluate the efficacy and safety of inhibition of Interleukin-1 receptor associated kinase 4 (IRAK4) in ameliorating the proinflammatory state and improving outcomes in severe COVID-19.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
68

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2021

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 6, 2021

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

April 23, 2021

Completed
2 months until next milestone

First Posted

Study publicly available on registry

June 22, 2021

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 6, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 6, 2022

Completed
Last Updated

June 22, 2021

Status Verified

June 1, 2021

Enrollment Period

1.2 years

First QC Date

April 23, 2021

Last Update Submit

June 17, 2021

Conditions

COVID-19 Pneumonia

Keywords

COVID-19 PneumoniaViral PneumoniaPneumoniaCOVID-19COVIDProtein Kinase InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionIRAK 4 InhibitorSARS-CoV-2 PneumoniaIRAK-4 Inhibitor in SARS-CoV-2 Pneumonia

Outcome Measures

Primary Outcomes (1)

  • Worsening based on the NIAID Ordinal scale

    Proportion of subjects worsened at end of treatment (Day 29), as defined by categories 7 and 8 in the 8-point NIAID scale of disease severity. 1. Not hospitalized, no limitations on activities. 2. Not hospitalized, limitation on activities and/or requiring home oxygen\*. 3. Hospitalized, not requiring supplemental oxygen\* - no longer requires ongoing medical care. 4. Hospitalized, not requiring supplemental oxygen\* - requiring ongoing medical care (COVID-19 related or otherwise). 5. Hospitalized, requiring supplemental oxygen\*. 6. Hospitalized, on non-invasive ventilation or high-flow oxygen devices\*\*. 7. Hospitalized, on invasive mechanical ventilation or ECMO. 8. Death. * For subjects on chronic home O2 supplementation (pre-morbid state), supplemental O2 is defined as ≥ home O2 requirement. * Use of non-invasive ventilation for chronic conditions (eg, Obstructive sleep apnea \[OSA\]) is not applicable.

    29 days

Secondary Outcomes (12)

  • Improvement based on the NIAID Ordinal scale

    29 days

  • Recovered based on the NIAID Ordinal scale

    29 days

  • mortality

    29 days

  • mortality

    61 days

  • Time to clinical improvement based on the NIAID Ordinal scale

    29 days

  • +7 more secondary outcomes

Other Outcomes (8)

  • Change from baseline in inflammatory parameters

    29 days

  • cytokine panel. Units of measurement for all cytokines in the panel is pg/ml

    29 days

  • SARS-CoV-2 viral load

    29 days

  • +5 more other outcomes

Study Arms (2)

PF-06650833 + Standard of Care treatment

ACTIVE COMPARATOR

Subjects randomized to the PF-06650833 arm of the study will receive 400 mg PF-06650833 (2 x 200 mg tablets) of the MR formulation orally QD under fasted conditions (preferably at least 4 hours after and 1.5 hours before a meal). Subjects who cannot take tablets PO will receive PF-06650833 200 mg IR suspension formulation every 6 hours (NG tube or OG tube, or equivalent). Subjects for whom concomitant administration of a strong inhibitor of CYP3A4 (eg, ritonavir) will have the dose reduced to either 200 mg MR or IR QD. All dosing of study drug will be in addition to current hospital SOC treatment that must include treatment targeting SARS-CoV-2.

Drug: PF-06650833

Placebo + Standard of Care treatment

PLACEBO COMPARATOR

Placebo will match the Active comparator in dosage form, dosage, frequency and duration.

Drug: Matching Placebo

Interventions

PF-06650833DRUG

PF-06650833 is an investigational, highly potent and selective, reversible inhibitor of IRAK4. IRAK4 is a serine, threonine kinase that is a key intracellular signaling node downstream of the myddosome-associated Toll-Like Receptors (TLR) 1, 2, 4, 5, 6, 7, 8, 9 and 10, and the interleukin (IL)-1 family receptors (IL-1R, IL-18R and IL-33R) that mediate much of the innate immune signaling. As an inhibitor of TLR signaling, PF-06650833 targets a different part of the immune system from the Janus kinase (JAK) inhibitors. Given the partial redundancy of innate immune signaling through IRAK4-independent TLR pathways and the lack of direct suppression of T- and B-cell signaling, PF-06650833 is unlikely to lead to exaggerated immunosuppression.

Also known as: IRAK 4 inhibitor
PF-06650833 + Standard of Care treatment
Matching PlaceboDRUG

Placebo will match the study drug in dose, formulation, route and frequency.

Also known as: Placebo
Placebo + Standard of Care treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Hospitalized adult male and female patients, including women of childbearing potential, at least 18 years of age, inclusive. Women of childbearing potential must agree to the protocol-specific contraception requirements.
  • Participant (or legally authorized representative) capable of giving signed informed consent.
  • Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection.
  • Evidence of pneumonia assessed by ALL of the following:
  • Radiographic imaging (eg, chest x-ray, chest computed tomography \[CT\] scan, etc.); AND
  • Clinical assessment (evidence of rales/crackles on exam); AND
  • SpO2 ≤94% on room air.
  • Evidence of increased inflammation as assessed by hsCRP \> ULN AND at least ONE of the following being \> ULN (as available):
  • Ferritin;
  • Procalcitonin;
  • D-dimer;
  • Fibrinogen;
  • LDH;
  • PT/PTT.

You may not qualify if:

  • Other medical condition other than COVID-19 or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study, eg, acute coronary syndrome.
  • 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.
  • Patients with positive hepatitis B surface antigen (HBsAg) will be excluded. Patients who are HBsAg negative but hepatitis B core antibody (HBcAb) positive will need a negative hepatitis B virus deoxyribonucleic acid (HBV DNA) to be allowed to enroll in the study; if the HBV DNA is positive, they will be not eligible.
  • Patients with a positive test for hepatitis C virus (hepatitis C virus antibody; HCV Ab) will need a negative hepatitis C virus ribonucleic acid (HCV RNA; or negative HCV Ab test) and normal liver function (as assessed by liver transaminases and bilirubin within protocol-permitted limits, and no other evidence of compromised liver synthetic ability (eg, albumin and coagulation tests within protocol-permitted limits) to be allowed to enroll in the study, provided other eligibility criteria are met.
  • Known history of human immunodeficiency virus (HIV) infection with a detectable viral load or CD4 count \<500 cells/mm3 (or patients for whom documentation of viral load or CD4 counts are not available) will be excluded; patients on highly active anti retroviral treatment, undetectable HIV viral load, and CD4 counts ≥500 cells/mm3 would be eligible).
  • Active hematologic cancer.
  • Metastatic or intractable cancer.
  • Pre-existing neurodegenerative disease.
  • Proven bacterial pneumonia, other serious infection, sepsis, and/septic shock.
  • Requirement for mechanical ventilation, or extracorporeal membrane oxygenation.
  • Severe hepatic impairment defined as Child-Pugh Class B or Class C at baseline.
  • Severe renal impairment with an estimated glomerular filtration rate (eGFR) \<50 mL/min/1.73 m2.
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bronx-Lebanon Hospital Center Health Care System

The Bronx, New York, 10457, United States

RECRUITING

MeSH Terms

Conditions

Pneumonia, ViralPneumoniaCOVID-19

Interventions

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

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsVirus DiseasesLung DiseasesRespiratory Tract DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus Infections

Study Officials

  • Giovanni Franchin, M.D, Ph.D

    Bronx-Lebanon Hospital Center Health Care System

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Swati Namballa, MBBS

CONTACT

4087180207snamball@bronxcare.org

Giovanni Franchin, M.D, Ph.D

CONTACT

6462456260GFranchi@bronxcare.org

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
The research Pharmacists are unblinded.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Study Principal Investigator

Study Record Dates

First Submitted

April 23, 2021

First Posted

June 22, 2021

Study Start

January 6, 2021

Primary Completion

March 6, 2022

Study Completion

May 6, 2022

Last Updated

June 22, 2021

Record last verified: 2021-06

Data Sharing

IPD Sharing
Will not share

Locations

US(1)