Influenza MedDRA version: 14.1 Level: PT Classification code 10022000 Term: Influenza System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Crucell Holland B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Subject must be a male or a female 18 years of age or older 2)Subject requires hospitalization. 3)Each subject or his or her legally acceptable representative must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. Consent may be given for an unconscious/incapacitated subject by a legally acceptable representative, according to local regulatory and ethical practice using a subject information sheet and informed consent form approved by the responsible Ethics Committee. When a subject is no longer unconscious/incapacitated, informed consent or assent (if consent not feasible) will be obtained from the subject at that time. 4)Subject must have a diagnosis of influenza A by rapid immunoassay, PCR or other approved test capable of typing influenza A and B (subtyping by PCR if available is preferable) 5) A woman must be either: •Not be of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 12 months); permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy •Of childbearing potential and agrees to practice two forms of highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g. established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject) for the duration of the study Note: If the childbearing potential changes after start of the study (e.g. woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must agree to begin two highly effective methods of birth control, as described above for the duration of the study. This screening assessment will not apply to unconscious/incapacitated subjects. 6)A woman of childbearing potential must have a negative serum (Beta human chorionic gonadotropin [Beta-hCG]) at screening. 7)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 e.g. either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. This screening assessment will not apply to unconscious/incapacitated subjects. 8)Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol. This screening assessment will not apply to unconscious/incapacitated subjects. When a subject is no longer unconscious/incapacitated, this criterion will be assessed at that time. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 178 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 118
Exclusion criteria
Exclusion criteria: 1)Subject is a female who is pregnant or breastfeeding. 2)Subject undergoing peritoneal dialysis, hemodialysis or hemofiltration. 3)Subject has presence of any pre-existing illness that, in the opinion of the investigator, would place the subject at an unreasonably increased risk through participation in this study. 4)Subject has prior treatment with an experimental mAb; or receipt of IgG within 3 months or on chronic mAb treatment prior to enrollment. 5)Subject has known or suspected hypersensitivity to any of the CR8020 or CR6261 excipients (sucrose, L-histidine L-histidine monohydrochloride, polysorbate 20). 6)Subject 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the rate of decline in quantitative viral load measured from nasopharyngeal (NP) swabs via quantitative RT-PCR (qRT-PCR) in subjects receiving the antibody matching their infection as compared to subjects receiving control treatment, within the subgroup of subjects infected with the influenza A subtype for which the mAb is active: •The efficacy of CR8020 will be evaluated within the subgroup of subjects infected with H3N2, where the active treatment group (receiving CR8020) will be compared to the control group (receiving inactive treatment, i.e. CR6261, or placebo). •The efficacy of CR6261 will be evaluated within the subgroup of subjects infected with H1N1, where the active treatment group (receiving CR6261) will be compared to the control group (receiving inactive treatment, i.e. CR8020, or placebo). ;Secondary Objective: •Clinical improvement as measured by the Influenza Intensity and Impact Questionnaire (Flu-iiQTM) .•Clinical course in ICU patients as measured by Sequential Organ Failure Assessment Score (SOFA), Lung Injury Score (LIS), and Oxygenation Index (OI) as compared to baseline •The rate of decline measured up to Day 8 by NP swabs in subjects not intubated at baseline and by ET aspirates in subjects intubated at baseline via qRT-PCR post-treatment. •Rate of decline in quantitative viral load post-treatment as measured by viral culture •Area under the curve (AUC) of viral load as measured by qRT-PCR •Length of overall hospital stay, defined as the number of days from randomization to discharge from hospital •Mortality (proportion of subjects who died) •Pharmacokinetics (PK) •Immunogenicity: anti-drug antibodies (ADAs) to CR8020 and CR6261 •Safety and tolerability;Primary end point(s): The rate of decline in viral load measured from NP swabs via qRT-PCR post-treatment estimated through a linear mixed model;Timepoint(s) of evaluation of this end point: up to Day 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1)Clinical improvement as evaluated by the slope of decline for each of the domains of the PRO questionnaire (Flu-iiQTM) separately. 2)Clinical course in ICU patients as measured by Sequential Organ Failure Assessment Score (SOFA), Lung Injury Score (LIS), and Oxygenation Index (OI) as compared to baseline. 3)The rate of decline measured by NP swabs in subjects not intubated at baseline and by ET aspirates in subjects intubated at baseline via qRT-PCR post-treatment. 4)Rate of decline in quantitative viral load post-treatment as measured by viral culture. 5)AUC for viral loads determined by qRT-PCR will be compared. 6)The length of overall hospital stay 7)Mortality rates will be compared between treatment and control groups.;Timepoint(s) of evaluation of this end point: 1)Randomization to Day 15 2)From screening to date of discharge or Day 15 3)Up to day 8 4)Up to Day 8 5)Up to Day 8 6) Date of randomization to date of discharge 7) From randomization to time of death | — |
Countries
Australia, Belgium, Brazil, Canada, France, South Africa, Spain, Sweden, United States
Contacts
Public ContactProgram Director
Crucell Vaccine Institute
Outcome results
None listed