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

Sponsor

Crucell Holland BV (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01992276

Collaborator

Division of Microbiology and Infectious Diseases (DMID) (Other), National Institutes of Health (NIH) (NIH)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: CR8020 Biological: CR6261 Biological: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2013

Anticipated Primary Completion Date :

Oct 1, 2014

Anticipated Study Completion Date :

Feb 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Rate of decline in quantitative viral load [Baseline to Day 8]

Secondary Outcome Measures

Clinical improvement [Baseline to Day 15]
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
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]
Rate of decline in quantitative viral load [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 [Baseline to Day 116]
Survival times measured from randomization to time of death

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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/

Contacts and Locations

Locations

	City	State	Country
1	Fresno	California	United States
2	Stanford	California	United States
3	Washington	District of Columbia	United States
4	Tampa	Florida	United States
5	Chicago	Illinois	United States
6	Maywood	Illinois	United States
7	Baltimore	Maryland	United States
8	Detroit	Michigan	United States
9	Royal Oak	Michigan	United States
10	Troy	Michigan	United States
11	Minneapolis	Minnesota	United States
12	Saint Louis	Missouri	United States
13	Hackensack	New Jersey	United States
14	Somers Point	New Jersey	United States
15	New York	New York	United States
16	Rochester	New York	United States
17	Winston-Salem	North Carolina	United States
18	Dayton	Ohio	United States
19	Wilkes Barre	Pennsylvania	United States
20	Nashville	Tennessee	United States
21	Houston	Texas	United States
22	Adelaide		Australia
23	Melbourne		Australia
24	Parkville - Vic		Australia
25	Westmead		Australia
26	Brussel		Belgium
27	Edegem		Belgium
28	Gent		Belgium
29	Leuven		Belgium
30	Belo Horizonte		Brazil
31	Campinas		Brazil
32	Curitiba		Brazil
33	Passo Fundo		Brazil
34	Porto Alegre		Brazil
35	Ribeirão Preto		Brazil
36	Sao Jose Do Rio Preto		Brazil
37	Sao Paulo		Brazil
38	São Paulo		Brazil
39	Sofia		Bulgaria
40	Toronto	Ontario	Canada
41	Toronto N/A		Canada
42	Toronto		Canada
43	Clermont-Ferrand		France
44	Limoges		France
45	Lyon		France
46	Paris		France
47	Rennes		France
48	St Priest-En-Jarez		France
49	Donaustauf		Germany
50	Jena		Germany
51	Leipzig		Germany
52	Potsdam		Germany
53	Amsterdam		Netherlands
54	Apeldoorn		Netherlands
55	Leiden		Netherlands
56	Utrecht		Netherlands
57	Benoni		South Africa
58	Durban		South Africa
59	Pretoria Gauteng		South Africa
60	Alicante		Spain
61	Barcelona		Spain
62	Córdoba		Spain
63	Elche		Spain
64	Madrid		Spain
65	San Sebastian		Spain
66	Santander N/A		Spain
67	Tarragona		Spain
68	Malmö		Sweden
69	Stockholm		Sweden
70	Uppsala		Sweden