COmbination Therapy With Baloxavir and Oseltamivir 1 for Hospitalized Patients With Influenza (The COMBO Trial 1) (COMBO 1)

• ClinicalTrials.gov Identifier: NCT04327791
• Recruitment Status: Recruiting
• First Posted: March 31, 2020
• Last Update Posted: March 9, 2023
• Sponsor: Bassett Healthcare
• Collaborators: Genentech, Inc.; Viroclinics Biosciences B.V.
• Information provided by (Responsible Party): Daniel Freilich, MD, Bassett Healthcare

Study Description

Brief Summary:

This is a randomized, double-blind, placebo-controlled Phase 2-like, investigator-directed trial of hospitalized patients with laboratory confirmed influenza. Eligible and consented patients will be randomly assigned, in a 1:1 ratio, to one of two groups: Group 1, the combination treatment group (oseltamivir and baloxavir); Group 2, the standard treatment group (oseltamivir and placebo).

Condition or disease	Intervention/treatment	Phase
Influenza	Drug: Baloxavir; Drug: Placebos	Phase 2; Phase 3

Detailed Description:

Up to 60 hospitalized patients with laboratory confirmed influenza who provide informed consent and meet trial inclusion/exclusion criteria.

Experimental Design and Methods In a randomized, double-blind, placebo-controlled Phase 2-like, investigator-directed trial, hospitalized patients with laboratory confirmed influenza meeting inclusion and exclusion criteria, will be provided information on the trial, offered enrollment, and enrolled randomly in a 1:1 ratio to one of two groups upon signing of the study's informed consent form: Group 1, the combination treatment group (oseltamivir and baloxavir); Group 2, the standard treatment group (oseltamivir and placebo).

• Group 1, the combination treatment group will receive oseltamivir and baloxavir

  • Oseltamivir: 75 mg po bid for 5 days
  • Baloxavir: 40 mg po once for wt < 80 kg OR 80 mg po once for wt >/= 80 kg

• Group 2, the standard treatment group will receive oseltamivir and placebo

  • Oseltamivir: 75 mg po bid for 5 days
  • Placebo: Once

Oseltamivir dosing may be reduced for patients with decreased renal function as follows, per treating physician:

• CrCl > 60 mL/minute: No dosage adjustment
• CrCl > 30 to 60 mL/minute: 30 mg po bid
• CrCl > 10 to 30 mL/minute: 30 mg po qd
• HD: 30 mg po once and 30 mg po after each HD session
• CAPD: 30 mg po once
• CRRT: 30 mg po qd After assignment of a unique study number after signing informed consent, baseline data will be collected at time 0 including personal and clinical information and protocol directed laboratory specimens - nasal swabs for influenza PCR for patients who only had a rapid antigen test and blood specimens for patients who consent to additional blood drawing (for improved efficacy and safety analyses; not required for enrollment). Patients will be given oseltamivir by their healthcare providers. Research personnel's only involvement for oseltamivir dosing will be to remind providers that earlier treatment improves efficacy. Patients will then be given a single dose of baloxavir or placebo by the study's CRC as per a computerized random allocation scheme with dose determined by weight (as above); the CRC will notify the patient's provider that the patient has been given the single (blinded) dose. At time 1, 2, 3, 4, 7, and 30 days, nasal swabs will again be obtained, clinical information will be obtained from the patient via interview and review of the EMR, and blood specimens for patients who consented to additional blood drawing. Follow up will continue for 30 days.

Efficacy and adjudicated safety data points will be assessed by a Data Monitoring Committee (DMC) quarterly and as needed throughout the trial.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: COmbination Therapy With Baloxavir and Oseltamivir 1 for Hospitalized Patients With Influenza (The COMBO Trial 1)
• Actual Study Start Date: April 3, 2020
• Estimated Primary Completion Date: June 1, 2024
• Estimated Study Completion Date: June 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: baloxavir; Baloxavir: 40 mg po once for wt < 80 kg OR 80 mg po once for wt >/= 80 kg	Drug: Baloxavir; administered PO once
Placebo Comparator: placebo; placebo po once	Drug: Placebos; administered PO once

Outcome Measures

Primary Outcome Measures :

1. Time to Clearance of Viral Shedding [ Time Frame: 30 days ]
   influenza viral titer obtained by nasal swab using qCulture

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

1. Adults >/= 18 years old
2. Laboratory confirmed influenza A and/or B (rapid test or PCR)
3. Able to be enrolled, randomized, and dosed with study drug within 8 hours of the decision to admit patient to hospital for treatment of influenza

4. Oseltamivir treatment ordered by clinical team AND patient is able to be enrolled:

   • Prior to the initial dose of oseltamivir OR
   • Within 60 minutes after the initial dose of oseltamivir
5. Subject or Legally Authorized Representative able to and willing to provide written informed consent
6. Able to commit to 30 days of follow up
7. Weight > 40 kg
8. SARS-CoV-2 PCR swab sent within 1 week of enrollment

Exclusion Criteria

1. ESRD not undergoing hemodialysis (HD) or peritoneal dialysis (CAPD)
2. Severe hepatic insufficiency, cirrhosis, acute or chronic liver failure
3. Nausea/vomiting, aspiration risk, or other conditions precluding the ability to use oral medications (if patient is NPO including meds) unless gastric tube use available (e.g., NG tube, G tube, etc.)
4. Influenza medication use within the prior week, other than the initial oseltamivir given during this hospitalization for this episode of influenza
5. Oseltamivir or baloxavir allergy or intolerance
6. Pregnancy (need negative pregnancy test (urine or blood) in reproductive age women)
7. Absence of dependable contraception in reproductive age women
8. Inability to obtain informed consent
9. Refusal of oseltamivir therapy by patient as baseline treatment

Contacts and Locations

Contacts

Contact: jennifer Victory, RN; 6075476965; jennifer.victory@bassett.org

Contact: Daniel Freilich, MD; 6075474586; daniel.freilich@bassett.org

Locations

United States, New York

Bassett Medical Center; Recruiting

Cooperstown, New York, United States, 13326

Contact: jennifer Victory, RN 607-547-6965 jennifer.victory@bassett.org

Principal Investigator: daniel freilich, MD

Sponsors and Collaborators

Bassett Healthcare

Genentech, Inc.

Viroclinics Biosciences B.V.

Investigators

• Principal Investigator: Daniel Freilich, MD; Bassett Medical Center

More Information

• Responsible Party: Daniel Freilich, MD, attending physician - hospitalist, Bassett Healthcare
• ClinicalTrials.gov Identifier: NCT04327791
• Other Study ID Numbers: 1579493
• First Posted: March 31, 2020
• Last Update Posted: March 9, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Baloxavir; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action