Duvelisib to Combat COVID-19

NCT04372602 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 202007009
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The exceedingly high mortality rates of severe and critical COVID-19 warrant the identification and evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. Based on preclinical data from this institution and others, the investigators hypothesize that PI3K inhibition with duvelisib could potentially quell aberrant hyperactivtation of the innate immune system, preferentially polarize macrophages, reduce pulmonary inflammation, and limit viral persistence, thereby improving patient outcomes.

Conditions

COVID-19

Keywords

COVID-19

Outcome Measures

Primary Outcomes (1)

• Overall Survival as Measured by Number of Participants Alive Through 28 Days

  Through 28 days

Secondary Outcomes (7)

• Length of Hospital Stay

  Through 28 days

• Length of ICU Stay

  Through 28 days

• Duration of Ventilator Use

  Through 28 days

• Duration of Vasopressors Use

  Through 28 days

• Duration on Renal Replacement Therapy

  Through 28 days

Study Arms (2)

Duvelisib

EXPERIMENTAL

-Duvelisib 25 mg twice daily for up to 10 days.

Drug: Duvelisib; Procedure: Peripheral blood draw

Placebo

SHAM COMPARATOR

-Placebo 25 mg twice daily for up to 10 days.

Procedure: Peripheral blood draw; Drug: Placebo

Interventions

Duvelisib DRUG

-For patients unable to administer orally, a duvelisib suspension will be administered through a nasogastric/orogastric tube.

Also known as: Copiktra

Duvelisib

Peripheral blood draw PROCEDURE

* First 10 patients enrolled * Screening, Day 2, Day 4, Day 8, Day 10, Day 15, and Day 29

Duvelisib; Placebo

Placebo DRUG

-Provided by Verastem

Placebo

Eligibility Criteria

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

You may qualify if:

• A diagnosis of advanced COVID-19 as defined both of the following:
• as a positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper respiratory tract (e.g. nasopharyngeal, nasal, oropharyngeal swab, or saliva) and, if possible, the lower respiratory tract (sputum, tracheal aspirate, or bronchoalveolar lavage), analyzed by a CLIA certified lab with an FDA approved assay.
• Critical disease manifested by any of the following:
• Chest imaging with ≥ 50% lung involvement
• Respiratory failure requiring invasive mechanical ventilation, non-invasive mechanical ventilation (eg. BiPAPA, OptiFlow), supplementary oxygen with FiO2 ≥ 6 LPM or extracorporeal membrane oxygenation (ECMO)
• Shock - defined as mean arterial pressure ≤ 65 mmHg unresponsive to 25ml/kg isotonic intravenous fluid resuscitation and/or requiring vasopressor support
• Cardiac dysfunction defined by:
• New global systolic dysfunction with ejection fraction ≤ 40%
• Takotsubo cardiomyopathy
• Patients who have received prior investigational or off-label agents for COVID-19 does not exclude eligibility.
• At least 18 years of age at the time of study registration
• Adequate hematologic function defined as absolute neutrophil count ≥1000/mm3 and platelet count ≥ 50,000/mm3 without growth factor or transfusion support for 7 days prior to screening.
• Creatinine-clearance ≥ 15 mL/minute or receiving renal replacement therapy
• Aminotransferase (AST/ALT) levels \<3x the upper limit of normal
• Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)

You may not qualify if:

• Known allergy or intolerance to duvelisib or another PI3K inhibitor.
• Known or suspected active viral (including CMV, HIV, hepatitis B, and hepatitis C), bacterial, mycobacterial, or fungal infection other than COVID-19. CMV viral load will be assessed at screening and those with viremia will be excluded. Other virologic testing not required unless infection is suspected.
• Pregnant and/or breastfeeding.
• Any uncontrolled intercurrent illness that would put the patient at greater risk or limit compliance with study requirements in the opinion of the investigator.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Verastem, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Goldsmith SR, Covut F, Fiala M, Xiang Z, Iqbal Z, Moore N, Bradtke E, Christen B, Rettig MP, Christ S, Gehrs L, Street E, Wallace N, Ritchey J, Gao F, Pachter J, Parikh B, Dubberke ER, DiPersio JF. Duvelisib for Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial. Open Forum Infect Dis. 2023 Oct 27;10(11):ofad518. doi: 10.1093/ofid/ofad518. eCollection 2023 Nov.

  PMID: 37953814 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

COVID-19

Interventions

duvelisib

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

Results Point of Contact

• Title: John DiPersio, M.D., Ph.D.
• Organization: Washington University School of Medicine

jdipersi@wustl.edu

314-454-8491

Study Officials

• John DiPersio, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Blocks of 10 patients will be used to allocate patients to duvelisib or placebo
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 4, 2020
• Study Start: October 12, 2020
• Primary Completion: February 6, 2022
• Study Completion: March 2, 2022
• Last Updated: March 6, 2023
• Results First Posted: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)