A Multinational Phase III Study of CS-8958 (MARVEL) (MARVEL)

A Randomized Double-blind Controlled Study of CS-8958 Versus Oseltamivir Phosphate in Patients With Influenza Virus Infection

The primary objective of this study is to confirm the efficacy of CS-8958 administered as a single inhaled low dose or single inhaled high dose by showing non-inferiority to oseltamivir phosphate using the time to alleviation of influenza illness. For safety evaluation, between-group comparisons will be made with regard to incidence of adverse events and other safety measures.

In a secondary objective, the optimum dosage of CS-8958 for this indication will be evaluated based on the efficacy and safety of single inhaled low or high dose.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Drug: CS-8958; Drug: CS-8958; Drug: oseltamivir phosphate

• Study Type: Interventional
• Enrollment (Actual): 1002
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hong-Kong, China
• Japan
  • Tokyo, Japan
• Korea, Republic of
  • Seoul, Korea, Republic of
• Taiwan
  • Taipei, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of influenza
• Axillary temperature of > or = to 37.5 degrees C

Exclusion Criteria:

• Infection by bacteria species and/or virus other than influenza virus
• Chronic respiratory disease
• Renal dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CS-8958 Low Dose; CS-8958 powder to be inhaled - low-dose arm	Drug: CS-8958; CS-8958 powder 20 mg to be inhaled one time. Oseltamivir phosphate placebo capsules 2 times per day for 5 days; Drug: CS-8958; CS-8958 powder 40 mg to be inhaled one time. Oseltamivir phosphate placebo capsules 2 times per day for 5 days
Experimental: CS-8958 High Dose; CS-8958 powder to be inhaled - high-dose arm	Drug: CS-8958; CS-8958 powder 20 mg to be inhaled one time. Oseltamivir phosphate placebo capsules 2 times per day for 5 days; Drug: CS-8958; CS-8958 powder 40 mg to be inhaled one time. Oseltamivir phosphate placebo capsules 2 times per day for 5 days
Active Comparator: Oseltamivir phosphate; oseltamivir phosphate oral capsules	Drug: oseltamivir phosphate; CS-8958 placebo powder to be inhaled one time. Oseltamivir phosphate oral capsules taken twice daily for 5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Alleviation of Influenza Illness	The time to illness alleviation which was defined as the time from the initiation of trial treatment to the beginning of the first 21.5-h period in which all influenza symptoms were "absent" or "mild." Patients recorded their severity of influenza symptoms (headache, myalgia/arthralgia, fatigue, chills/sweats, nasal symptom, sore throat, and cough) 4 times daily for 15 days. Patients whose influenza symptoms had not been alleviated at the time of their withdrawal from the study or at the end of the observation period were censored.	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time for Body Temperature to Return to Normal	Time for return to normal axillary temperature was was defined as the time until the beginning of the first 21.5-hour period in which the axillary temperature returned to 36.9°C. Patients recorded their axillary temperature 4 times daily for 15 days. Patients whose axillary temperature had not been returned to 36.9°C at the time of their withdrawal from the study or at the end of the observation period were censored.	15 days

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.

Publications and helpful links

General Publications

• Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y; MARVEL Study Group. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: A double-blind, randomized, noninferiority clinical trial. Clin Infect Dis. 2010 Nov 15;51(10):1167-75. doi: 10.1086/656802. Epub 2010 Oct 11.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: December 4, 2008
• First Submitted That Met QC Criteria: December 4, 2008
• First Posted (Estimate): December 5, 2008

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: Influenza; Neuraminidase inhibitor
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: CS8958-A-J301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR