Assessment of Efficacy of CR8020 and CR6261, Monoclonal Antibodies, Against Influenza Infection

Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of CR8020 and CR6261 in Hospitalized Patients With Influenza A Infection

The purpose of this study is to evaluate the rate of decline in quantitative viral load measured in hospitalized patients with Influenza A infection

Study Overview

• Status: Withdrawn
• Conditions: Influenza
• Intervention / Treatment: Biological: CR8020; Biological: CR6261; Biological: Placebo

Detailed Description

This is a randomized, placebo-controlled, double-blind phase IIa proof-of-concept study, designed to evaluate the effect of CR8020, CR6261, or placebo in hospitalized patients with influenza A infection that are receiving standard of care. Up to 262 participants will be randomized to receive 30 mg/kg of CR8020, 30 mg/kg of CR6261, or placebo. The study duration will be approximately 117 days for each participant. Prior to enrollment, participants will be screened to assess their eligibility. Eligible participants will be randomized to CR8020, CR6261, or placebo and study drug will be administered on Day 1. Participants will be followed up for 115 days in 9 visits on Days 2 to 8, Day 29, and Day 116 (end of study). After hospital discharge, the remaining follow-up visits will be performed as outpatient visits.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
  • Melbourne, Australia
  • Parkville - Vic, Australia
  • Westmead, Australia
• Belgium
  • Brussel, Belgium
  • Edegem, Belgium
  • Gent, Belgium
  • Leuven, Belgium
• Brazil
  • Belo Horizonte, Brazil
  • Campinas, Brazil
  • Curitiba, Brazil
  • Passo Fundo, Brazil
  • Porto Alegre, Brazil
  • Ribeirão Preto, Brazil
  • Sao Jose Do Rio Preto, Brazil
  • Sao Paulo, Brazil
  • São Paulo, Brazil
• Bulgaria
  • Sofia, Bulgaria
• Canada
  • Toronto, Canada
  • Toronto N/A, Canada
  • Ontario
    • Toronto, Ontario, Canada
• France
  • Clermont-Ferrand, France
  • Limoges, France
  • Lyon, France
  • Paris, France
  • Rennes, France
  • St Priest-En-Jarez, France
• Germany
  • Donaustauf, Germany
  • Jena, Germany
  • Leipzig, Germany
  • Potsdam, Germany
• Netherlands
  • Amsterdam, Netherlands
  • Apeldoorn, Netherlands
  • Leiden, Netherlands
  • Utrecht, Netherlands
• South Africa
  • Benoni, South Africa
  • Durban, South Africa
  • Pretoria Gauteng, South Africa
• Spain
  • Alicante, Spain
  • Barcelona, Spain
  • Córdoba, Spain
  • Elche, Spain
  • Madrid, Spain
  • San Sebastian, Spain
  • Santander N/A, Spain
  • Tarragona, Spain
• Sweden
  • Malmö, Sweden
  • Stockholm, Sweden
  • Uppsala, Sweden
• United States
  • California
    • Fresno, California, United States
    • Stanford, California, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Tampa, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
    • Maywood, Illinois, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Michigan
    • Detroit, Michigan, United States
    • Royal Oak, Michigan, United States
    • Troy, Michigan, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New Jersey
    • Hackensack, New Jersey, United States
    • Somers Point, New Jersey, United States
  • New York
    • New York, New York, United States
    • Rochester, New York, United States
  • North Carolina
    • Winston-Salem, North Carolina, United States
  • Ohio
    • Dayton, Ohio, United States
  • Pennsylvania
    • Wilkes Barre, Pennsylvania, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Participant requires hospitalization/ Each participant or his or her legally acceptable representative must sign an informed consent form/ Participant must be able to start the infusion within 36 hours from the time the screening specimen was collected/ A woman must either be not of childbearing potential or of childbearing potential and agrees to practice two forms of highly effective method of birth control/ A woman of childbearing potential must have a negative serum (beta human chorionic gonadotropin [beta hCG]) at screening/ A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control/

Exclusion Criteria:

Participant is a female who is pregnant or breastfeeding/ Participant undergoing peritoneal dialysis, hemodialysis or hemofiltration/ Participant has presence of any pre-existing illness that, in the opinion of the investigator, would place the participant at an unreasonably increased risk through participation in this study/ Participant has prior treatment with an experimental mAb; or receipt of IgG within 3 months or on chronic mAb treatment prior to enrollment/ Participant has known or suspected hypersensitivity to any of the CR8020 or CR6261 excipients (sucrose, L-histidine L-histidine monohydrochloride, polysorbate 20)/ Participant received an investigational product (including investigational vaccines) or used an investigational medical device within 60 days before the planned start of treatment, is currently enrolled in an interventional investigational study, or is an employee of the investigational site/

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: CR8020; Investigational monoclonal antibody against influenza A viruses	Biological: CR8020; 30 mg/kg administered as a single 2-hour intravenous infusion on Day 1; Other Names: CR8020 30 mg/kg by iv infusion
Experimental: CR6261; Investigational monoclonal antibody against influenza A viruses	Biological: CR6261; 30 mg/kg administered as a single 2-hour intravenous infusion on Day 1; Other Names: CR6261 30 mg/kg by iv infusion
Placebo Comparator: Placebo; Dextrose: 5% in water	Biological: Placebo; Administered as a single 2-hour intravenous infusion on Day 1; Other Names: Placebo by iv infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of decline in quantitative viral load	Baseline to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of decline in quantitative viral load		Baseline to Day 8
Clinical improvement	Daily influenza symptoms and signs: Four domains from the Influenza Intensity and Impact Questionnaire will be evaluated (scored 0-3: none, mild, moderate, severe): -Influenza symptoms (respiratory and systemic domains Impact on daily activities Impact on emotions Impact on others	Baseline to Day 15
Rate of decline in quantitative viral load (subjects not intubated at baseline)		Baseline to Day 8
Rate of decline in quantitative viral load (subjects intubated at baseline)		Baseline to Day 8
Incidence of adverse events		Baseline to Day 116
Incidence of serious adverse events		Baseline to Day 116
Area under the curve of viral load		Baseline to Day 8
Clinical course for ICU patients		Baseline to Day 8
Length of hospital stay		The duration of hospital stay, an expected average of 7 days
Survival times	Survival times measured from randomization to time of death	Baseline to Day 116

Collaborators and Investigators

• Sponsor: Crucell Holland BV
• Collaborators: National Institutes of Health (NIH); Division of Microbiology and Infectious Diseases (DMID)

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): October 1, 2014
• Study Completion (Anticipated): February 1, 2015

Study Registration Dates

• First Submitted: November 11, 2013
• First Submitted That Met QC Criteria: November 18, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Estimate): March 4, 2014
• Last Update Submitted That Met QC Criteria: March 3, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Treatment; Influenza; Monoclonal Antibody; Virus; Immunization
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: CR102576; 2013-003341-41 (EudraCT Number); CR6261CR8020FLZ2001 (Other Identifier: Crucell Holland BV)