Clinical Trials Register

Summary
EudraCT Number:	2015-000574-35
Sponsor's Protocol Code Number:	VIS410-201
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-03-25
Trial 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

Belgium - FPS Health-DGM

A.2

EudraCT number

2015-000574-35

A.3

Full title of the trial

A Phase 2a Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Antiviral Activity of a Single Intravenous Dose of VIS410 in Healthy Subjects after a Viral Inoculation with Influenza A (H1N1).

A.3.1

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

A.4.1

Sponsor's protocol code number

VIS410-201

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	Visterra, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Visterra, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Visterra, Inc.
B.5.2	Functional name of contact point	-
B.5.3	Address:
B.5.3.1	Street Address	One Kendall Square, Suite B3301, Building 300
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	MA 02139
B.5.3.4	Country	United States
B.5.4	Telephone number	+1617498-1070 337
B.5.6	E-mail	chay@visterrainc.com

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.3.2	Product code	VIS410
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.1	CAS number	-
D.3.9.2	Current sponsor code	VIS410
D.3.9.3	Other descriptive name	-
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	25
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)	No
D.3.11.7	Plasma derived medicinal product	No
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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal antibody

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	Solution for 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

Influenza A (H1N1) infection

E.1.1.1

Medical condition in easily understood language

Flu

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10063211
E.1.2	Term	Influenza A virus IgG
E.1.2	System Organ Class	100000004848

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 objectives are to assess the safety profile of VIS410 (Part 1, 2 and 3) and the effect of VIS410 on the area under the curve of viral shedding over time (viral AUC) in healthy subjects after viral inoculation with influenza A (H1N1) (Part 1 only).

E.2.2

Secondary objectives of the trial

Secondary objectives are to:
- Assess the effects of VIS410 on viral shedding.
- Assess the pharmacokinetics of VIS410 in serum.
- Assess the immunogenicity of VIS410.
- Assess the effect of VIS410 on clinical symptoms.
- Assess antibody to challenge strain.
- Assess the effect of different pretreatments on the safety and tolerability of VIS410 in healthy subjects after viral inoculation with influenza A (H1N1).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent prior to any procedures and be available for all study visits.
2. Male or female subjects of age 18-45 years, inclusive, at the time of informed consent.
3. Women should fulfill one of the following criteria:
a. Post-menopausal; either amenorrhea ≥ 12 months or follicle stimulating hormone > 40 mIU/mL.
b. Surgically sterile; bilateral oophorectomy, hysterectomy, or tubal ligation.
c. Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from screening until the end of the study. The following is considered adequate contraception: combination of an established form of hormonal contraception or an intrauterine device with a physical barrier method (condom, diaphragm or cervical/vault cap). The combination of 2 barrier methods, periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not considered acceptable methods of contraception. The use of contraception does not apply if the male partner has been vasectomized at least 6 months prior to dosing.
d. Must be sexually inactive by abstinence which is consistent with the preferred and usual lifestyle of the subject.
4. Women of childbearing potential must have a negative pregnancy test at screening (serum) and on Day -2 (urine).
5. Non-vasectomized (or vasectomized less than 6 months prior to dosing) male subjects who have a female partner of childbearing potential must use an effective birth control method (see Inclusion Criterion 3) when having heterosexual intercourse, for the entire duration of the study.
6. Healthy, as determined by a satisfactory medical assessment with no clinically significant or relevant abnormalities in medical history, physical examination, vital signs, ECG, lab evaluations at screening, as assessed by the investigator.
7. Able to understand and comply with planned study procedures and restrictions.
8. Seronegative for the challenge virus (HAI ≤ 10) not more than 4 weeks before dosing.
9. Non- smoker and non-habitual smoker (habitual smokers are persons who smoke more than 4 cigarettes or other tobacco products on a weekly basis) and agree to not use tobacco products during confinement.
Note: In case of an out-of-range clinical laboratory test, vital sign, or ECG value that will determine a subject’s eligibility, or in case of a positive drug screen, a retest can be done. Results of this retest must be available prior to viral inoculation (Day 1) and if abnormal, must be nonclinically significant for a subject to be enrolled in the study.

E.4

Principal exclusion criteria

1. Known or suspected intolerance or hypersensitivity to the investigational study drug or virus, or closely related compounds (e.g., other monoclonal antibodies) or any of the stated ingredients, including egg allergies or any moderate to severe allergic disorder, or any suspected intolerance or hypersensitivity to the possible pretreatment drugs (diphenhydramine, ranitidine, montelukast, or paracetamol for Part 1 only; diphenhydramine, ranitidine, montelukast, or ibuprofen for Part 2 only; pretreatments of Part 3 are selected based on Part 2).
2. Has an acute or chronic medical condition that, in the opinion of the investigator, would render the investigational study drug unsafe or would interfere with the evaluation of the responses, including but not limited to, cardiovascular, respiratory, autoimmune, or immune suppression conditions.
3. Subjects receiving medications that affect the immune system including systemic steroids and subjects on chronic medications where the dose has not been stable for at least 3 months. The use any of concomitant therapies is prohibited during the study, except for contraception and paracetamol (as per license).
4. Significant adulthood history of seasonal hay fever or a seasonal allergic rhinitis or perennial allergic rhinitis or chronic or nasal or sinus condition such as chronic sinusitis.
5. Diastolic blood pressure (DBP) < 50 or > 90 mmHg, a systolic BP (SBP) < 100 or > 150 mmHg, a pulse < 40 or > 100 bpm after resting in supine position for 5 minutes.
6. Subjects who have received any vaccination within the last 3 months or influenza vaccine within the last 6 months or who anticipate receiving this during the study.
7. Subjects with a confirmed diagnosis of influenza A within the last 6 months prior to screening.
8. Has a history of receiving monoclonal antibody, immunoglobulin or other blood products within 3 months prior to enrolment in this study or planned administration during the study period.
9. Donation (500 mL) of blood or blood products (e.g. plasma, platelets) within 3 months prior to or intention to donate blood during the study.
10. Subjects with abnormal nasal structure (including septal deviation and nasal polyps), chronic sinusitis, or reason (i.e., intolerance) that in the opinion of the investigator complicates nasopharyngeal swabbing.
11. Presence of lung disease, asthma, or chronic obstructive pulmonary disease.
12. Has a history of alcohol or drug abuse in the last year or has a positive screen for drugs of abuse (amphetamines, benzodiazepines, cocaine, methadone, or opiates) or alcohol at screening or Day -2.
13. A positive human immunodeficiency virus (HIV) antibody screen, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody screen.
14. Cancer or treatment for cancer, within 3 years, excluding basal cell carcinoma of the skin, which is allowed.
15. Presence of immunosuppression or any medical condition that may be associated with impaired immune responsiveness, including but not limited to, diabetes mellitus and inflammatory bowel disease.
16. Anticipated presence of a household contact with potential immunosuppression (in the opinion of the investigator), either as a result of disease and/or therapy.
17. History of Guillain-Barré syndrome.
18. Current professional activity as a healthcare worker who will return to work within 2 weeks following challenge.
19. Anticipated presence of a pregnant household contact, within 2 weeks following challenge.
20. Women who are pregnant or breast-feeding, or consider becoming pregnant.
21. Acute disease within 2 weeks prior to challenge, defined as the presence of a moderate or severe illness with or without fever (as determined by the investigator through medical history and physical examination), or presence of a fever ≥ 38ºC oral.
22. Elevated white blood cell count above 10.90 x 109/L or an absolute neutrophil count above 7.5 x 109/L.
23. Current enrollment in any other investigational drug study or disease study or participation in an investigational drug study within 90 days prior to Day 1 or within 5 half-lives of the investigational compound, whichever is longer.
24. Any other reasons for which the investigator considers the subject unfit for the study, including anorexia, obesity, or significant uncontrolled medical, neurological or psychiatric illness (acute or chronic) as assessed by the investigator.

E.5 End points

E.5.1

Primary end point(s)

- The proportion of subjects with post-infusion AEs including hypersensitivity reaction, anaphylactic reaction and other AEs occurring within 1 h of the completion of dosing;
- The proportion of subjects with AEs and SAEs;
- The difference between VIS410 and placebo treatment groups in viral AUC by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from nasopharyngeal swabs (Part 1 only).

E.5.1.1

Timepoint(s) of evaluation of this end point

- Within 1 h of the completion of the dosing
- Throughout duration of trial
- At the end of the trial

E.5.2

Secondary end point(s)

- The difference between VIS410 and placebo treatment groups in viral AUC (tissue culture infective dose that induces a pathological change in 50% of cell culture isolates [TCID50]) from nasopharyngeal swabs (Part 1 only);
- Peak viral load and time to cessation of viral shedding (qRT-PCR and TCID50) (Part 1 alone and pooled data [Part 1 + Part 2]);
- VIS410 PK parameters (Cmax, tmax, AUC extrapolated to infinity [AUC0-∞], AUC calculated between time of administration and time t [AUC0-t], t1/2, volume of distribution (Vd), clearance [CL]) in serum;
- Titer of serum antibody to challenge strain;
- Titer of anti-VIS410 antibody positive samples;
- The incidence, severity and duration of signs and symptoms of influenza-like illness as reported by the subjects and assessed by the investigator after virus challenge followed by a single IV dose of VIS410.
- The incidence, severity and duration of gastrointestinal signs and symptoms as reported by the subjects and assessed by the investigator after virus challenge followed by administration of different pre-treatments prior to a single IV dose of VIS410.

E.5.2.1

Timepoint(s) of evaluation of this end point

- At the end of the trial
- At the end of the trial
- At the end of the trial
- At the end of the trial
- At the end of the trial
- At the end of the trial

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

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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)

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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 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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-04-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-04-08

P. End of Trial
P.	End of Trial Status	Completed

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