Clinical Trials Register

Summary
EudraCT Number:	2014-004271-22
Sponsor's Protocol Code Number:	INSIGHTPROTOCOL006
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-10-06
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Greece - EOF

A.2

EudraCT number

2014-004271-22

A.3

Full title of the trial

Anti-Influenza Hyperimmune Intravenous Immunoglobulin Clinical Outcome Study (INSIGHT 006: FLU-IVIG)

Μελέτη Κλινικών Εκβάσεων Χορήγησης Αντιικής Υπεράνοσης Ενδοφλέβιας Αιμοσφαιρίνης

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Anti-Influenza Hyperimmune Intravenous Immunoglobulin Clinical Outcome Study

Μελέτη Κλινικών Εκβάσεων Χορήγησης Αντιικής Υπεράνοσης Ενδοφλέβιας Αιμοσφαιρίνης

A.3.2

Name or abbreviated title of the trial where available

(INSIGHT 006: FLU-IVIG)

A.4.1

Sponsor's protocol code number

INSIGHTPROTOCOL006

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02287467

A.5.4

Other Identifiers

Name:

ClinicalTrials.gov Identifier

Number:

NCT02287467

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Regents of the University of Minnesota
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical Research Coucil Clinical Trials Unit at University College London
B.5.2	Functional name of contact point	Chief Investigator- Sarah Pett
B.5.3	Address:
B.5.3.1	Street Address	125 Kingsway
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC2B 6NH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02076704618
B.5.5	Fax number	02076704817
B.5.6	E-mail	s.pett@ucl.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Anti-Influenza Immune Globulin Intravenous Injection (Anti-Influenza IVIG)
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Anti-Influenza Intravenous Immunoglobulin
D.3.9.2	Current sponsor code	Lot # 11300369
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Anti-Influenza Intravenous Immunoglobulin
D.3.9.2	Current sponsor code	Lot #11400643
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	mg/l milligram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	Yes
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Infleunza

E.1.1.1

Medical condition in easily understood language

Flu

E.1.1.2

Therapeutic area

Health Care [N] - Environment and Public Health [N06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10022000
E.1.2	Term	Influenza
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to compare the clinical status of patients in the IVIG and placebo groups at 7 days of follow-up using an ordinal outcome with 6 clinical states.
Specifically, patients will be categorized into one of the following 6 mutually exclusive categories on Day 7:
1) death;
2) in the intensive care unit (ICU);
3) non-ICU hospitalization, requiring supplemental oxygen;
4) non-ICU hospitalization, not requiring supplemental oxygen;
5) not hospitalized, but unable to resume normal activities; or
6) not hospitalized with resumption of normal activities.

The rationale behind this approach is to estimate in a clinically meaningful way whether the study drug has had a favourable clinical impact on the patient.

E.2.2

Secondary objectives of the trial

a. To compare participants in the IVIG and placebo groups for the following secondary outcomes:
• Change from baseline to Day 3 in NEW* score assessment
• The ordinal primary outcome assessed at Days 1-7, 14 and 28
• Number of days hospitalized
• Composite of mortality or hospitalization at Days 7, 14 and 28
• Requirement for invasive mechanical ventilation or admission to the ICU (among those not enrolled from the ICU)
• Mortality
• Complications of influenza such as bronchitis and pneumonia
• Percent of patients shedding virus at Day 3

*The NEW score is a simple severity of illness scoring system that the Royal College of Physicians, UK has developed and validated. It scores physiological parameters that would be routinely collected in hospitalised patients including pulse, respiratory rate, oxygen saturation, blood pressure, pulse and level of consciousness (i.e. alert vs. not).

b. To compare the IVIG and placebo groups for haemagglutination inhibition titre (influenza

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

INSIGHT PROTOCOL No. 004: Genomics: Version 2.0, 27 August 2013
Only patients enrolled in an INSIGHT study such as FLU-IVIG can enrol in this genomics sub study. The purpose of this genomics sub study is to obtain a single whole blood sample from which DNA will be extracted. This human DNA will be used to study various immune response genes and other genetic variants that may be associated with a worse outcome from influenza or its complications.

E.3

Principal inclusion criteria

1. Signed informed consent
2. Age ≥ 18 years of age
3. Locally determined positive influenza test (by PCR or other nucleic acid test, or by rapid Ag) from a specimen obtained within 2 days prior to randomization
4. Onset of illness no more than 7 days before randomization, defined as when the patient first experienced at least one respiratory symptom or fever
5. Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician.
6. For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least 1 form of hormonal or barrier contraception through Day 28 of the study
7. Willingness to have blood and respiratory samples obtained and stored
8. NEW score ≥ 2 at screening

E.4

Principal exclusion criteria

1. Women who are pregnant or breast-feeding
2. Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin
3. Prior treatment with any investigational drug therapy within 30 days prior to screening
4. History of allergic reaction to blood or plasma products (as judged by the site investigator)
5. Known IgA deficiency
6. A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis
(e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy)
7. Presence of any pre-existing illness that, in the opinion of the site investigator, would place the individual at an unreasonably increased risk through participation in this study
8. Patients who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol
9. Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the patient (e.g., decompensated congestive heart failure)
10. Receiving extracorporeal membrane oxygenation (ECMO)
11. Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is an ordinal outcome at Day 7 that has 6 mutually exclusive categories:
1. death;
2. in the intensive care unit (ICU);
3. non-ICU hospitalization, requiring supplemental oxygen;
4. non-ICU hospitalization, not requiring supplemental oxygen;
5. not hospitalized, but unable to resume normal activities; or
6. not hospitalized with full resumption of normal activities.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 0, 1, 2 (phone or face-to-face), 3, 7, 14, 28

E.5.2

Secondary end point(s)

Other endpoints include:
• Change from baseline to Day 3 in NEW score
• The ordinal primary outcome assessed at Days 1-7, 14 and 28
• Number of days hospitalized
• Composite of mortality or hospitalization at Days 7, 14 and 28
• Among those not enrolled in the ICU, requirement for invasive mechanical ventilation or admission to the ICU
• Percent of patients shedding virus at Day 3
• HAI antibody level changes through Day 7
• Grade 3 and 4 adverse events
• Serious adverse events
• Percent of patients developing bronchitis, pneumonia or other complications through Day 28
• Mortality

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 0, 1, 2 (phone or face-to-face), 3, 7, 14, 28

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.6.13.1

Other scope of the trial description

Clinical outcome

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Germany

Greece

Spain

Sweden

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1