Clinical Trials Register

Summary
EudraCT Number:	2013-004036-30
Sponsor's Protocol Code Number:	ALS-8176-502
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-10-23
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

UK - MHRA

A.2

EudraCT number

2013-004036-30

A.3

Full title of the trial

A Randomised, Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of Multiple Doses of Orally Administered ALS-008176 Against Respiratory Syncytial Virus Infection in the Virus Challenge Model

A.3.1

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

A study to compare ALS-008176 with a placebo to evaluate the safety, what the body does to the drug and how the drug effects the action of respiratory syncytial viral infection in healthy volunteers. The study uses multiple doses which are given orally.

A.3.2

Name or abbreviated title of the trial where available

Phase 2a, double blind, placebo-controlled, viral challenge study

A.4.1

Sponsor's protocol code number

ALS-8176-502

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	Alios BioPharma
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	Alios Biopharma
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	Alios BioPharma
B.5.2	Functional name of contact point	John Fry
B.5.3	Address:
B.5.3.1	Street Address	260 East Grand Avenue, 2nd Floor
B.5.3.2	Town/ city	San Francisco
B.5.3.3	Post code	CA 94080
B.5.3.4	Country	United States
B.5.4	Telephone number	+16506355543
B.5.5	Fax number	+16508720584
B.5.6	E-mail	clinicaldevelopment@aliosbiopharma.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	ALS-008176
D.3.4	Pharmaceutical form	Powder for oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	N/A
D.3.9.2	Current sponsor code	ALS-008176
D.3.9.3	Other descriptive name	C12041850-E
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	N/A
D.3.9.2	Current sponsor code	ALS-008176
D.3.9.3	Other descriptive name	C12041850-E
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	N/A
D.3.9.2	Current sponsor code	ALS-008176
D.3.9.3	Other descriptive name	C12041850-E
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
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	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	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	Oral solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Respiratory Syncytial Virus (RSV) infection

E.1.1.1

Medical condition in easily understood language

Respiratory Virus

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	16.1
E.1.2	Level	HLT
E.1.2	Classification code	10038717
E.1.2	Term	Respiratory syncytial viral infections
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the antiviral effect of oral ALS-008176 compared to placebo after inoculation with RSV-A Memphis 37b virus.

E.2.2

Secondary objectives of the trial

To evaluate ALS-008176 compared to placebo in healthy volunteers inoculated with RSV in terms of:
•Safety and tolerability
•PK profile of ALS-008176 and its metabolites (e.g., ALS-008112, and ALS-008144)
•Relationship between the PK and PD of ALS-008176 (and its metabolites)
•Effect of on clinical symptoms of RSV infection
•Development of viral resistance to ALS-008176

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 18 to 45 years, inclusive.

2. In good health with no history of major medical conditions from the medical history, physical examination, and routine laboratory tests as determined by the Investigator.

3. A total body weight ≥50 kg and a BMI of >18. If the BMI is above 30 the subject may be included if the waist measurement is less than 102 cm (male), or less than 88 cm (female).

4. Sexual history:
•True abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception].
Or
•The following criteria are applicable to partners in a relationship where the partners are of the opposite sex (i.e. the criteria do not apply to those in a same sex relationship):
(a)Male subjects must use highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at entry to quarantine, and continuing until 90 days after dosing with IMP.
(b)In addition, male subjects must not donate sperm following discharge from quarantine until 90 days after dosing with IMP.
(c)Female subjects must:
- be post-menopausal females- defined as a history of amenorrhea for at least two years
- or have documented status as surgically sterile or post hysterectomy,
or,
- if of childbearing potential, must have a negative blood pregnancy test at screening and must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at entry to quarantine and continuing until 90 days after dosing with IMP.
Acceptable forms of effective contraception include:
- Established (i.e. a minimum of 2 weeks prior to admission) use of oral, injected or implanted hormonal methods of contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).

5. An informed consent document signed and dated by the subject and the Investigator.

6. Sero-suitable for the challenge virus

E.4

Principal exclusion criteria

1. Screening/Day -2 or Day -1 laboratory result outside the reference range .
•Hemoglobin and reticulocyte counts ≥ the lower limit of normal for healthy subjects.
•a creatinine clearance < 50 mL/min
•a Screening ALT or AST > 1.5 X ULN
2. Use/anticipated use during the study of concomitant medications, including vitamins or herbal and dietary supplements within the specified windows:
- Herbal supplements within 7 days before the first study drug dose
- Chronically used medications, vitamins or dietary supplements, including any medication known to be an inducer or inhibitor of CYP450 enzymes, within 21 days before the first dose.
- Over the counter medications (with the exception of infrequent use of NSAIDs (e.g., ibuprofen) or paracetamol) within 7 days before the first study drug dose (≤3 g paracetamol or ibuprofen will be allowed prior to first study drug dose)
3. Subjects who are breastfeeding or who have been pregnant within 12 months prior to the study or who have a positive pregnancy test at any point during screening or prior to inoculation/dosing.
4. Any history or evidence of any clinically significant cardiovascular, dermatological, gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychiatric, renal, and/or other major disease.
a) Eczema/atopic dermatitis except subjects with clinically mild symptoms may be included
b) Psoriasis
c) Mild or moderate depressive episode(s) which occurred two or more years ago, with good evidence of preceding stressors and which resolved within approximately three months, may be included
•Any concurrent serious illness that may interfere with a subject completing the study.
5. Abnormal pulmonary function
6. History or evidence of autoimmune disease or known immunodeficiency of any cause – with the exception of eczema/atopic dermatitis
7. history of asthma, COPD, pulmonary hypertension, reactive airway disease, or chronic lung condition
8. History of childhood asthma before the age of 12 years is acceptable provided the subject is asymptomatic without treatment. Subjects with a single episode of wheezing after age 12 years can be included provided the episode is more than four years ago and did not require a hospital admission and/or oral steroids.
9. Positive human immunodeficiency virus, active hepatitis A, B, or C test.
10. Any significant abnormality altering the anatomy of the nose or nasopharynx.
11. Any clinically significant history of epistaxis
12. Any nasal or sinus surgery within six months of inoculation.
13. Recurrent history of fainting.
14. Twelve lead ECG recording with clinically relevant signs of pathology and conduction disturbances.
15. Confirmed positive test for drugs of abuse to be clinically significant.
16. Venous access deemed inadequate for the demands of the study.
17. Any known allergies to the excipients in the challenge virus inoculum.
18. Health care workers who work in units with severely immuno-compromised patients
19. Presence of household member or close contact who:
•has known immunodeficiency
•is receiving immunosuppressant medication
•is undergoing or soon to undergo cancer chemotherapy
•has been diagnosed with emphysema, COPD, or other severe lung disease
•has received a bone marrow or solid organ transplant
•resides in a nursing home.
20. •Evidence of vaccinations within the four weeks prior to inoculation/dosing.
•Intention to receive any vaccination(s) before the Day 28 Follow Up Visit
21. Those employed or immediate relatives of those employed at RVL or the Sponsor.
22. Receipt of blood or blood products, or loss of ≥ 450 mL of blood during the three months prior to inoculation.
23. Use within seven days prior to inoculation/dosing of any other medication or product for symptoms of hay fever, rhinitis, nasal congestion or respiratory tract infections including the use of nasal steroids
24. •Receipt of any investigational drug within three months prior to inoculation/ first dosing
•Receipt of more than three investigational drugs within the previous 12 months.
•Prior inoculation with the same strain of respiratory virus.
•Prior inoculation with a respiratory virus within one year prior to the day of inoculation/first dosing
•Prior participation in another Human Viral Challenge Study in the preceding 12 months.
25. •Receipt of systemic glucocorticoids or systemic antiviral drugs within six months prior to inoculation/dosing
•Receipt of any systemic chemotherapy agent, immunoglobulins or any other cytotoxic or immunosuppressive drugs at any time.
26. •Presence of significant respiratory symptoms existing on the day of inoculation or dosing
•History suggestive of respiratory infection within 14 days prior to admission to the unit.
27. Subjects who have a significant history of any tobacco use at any time
28. Any other finding that deems the subject unsuitable for the study.

E.5 End points

E.5.1

Primary end point(s)

Reduction in AUC0-t of RSV-A Memphis 37b viral load as determined by quantitative PCR assay of nasopharyngeal wash.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 2-12 and follow up visit 1 & 2

E.5.2

Secondary end point(s)

1. Safety data including, but not limited to, tabulation of adverse events (AEs), physical examinations, spirometry, vital signs, 12-lead ECGs and clinical laboratory results (including chemistry, haematology, and urine).
2. PK parameters of ALS-008176, ALS-008112 and ALS-008144 (and other metabolites as applicable) in plasma following repeat dose administration: Cmax, Cmin, Tmax, t1/2, CL/F and Vdss/F (excluding metabolites), AUC0-12h, AUC12-24h AUC0-24h, and AUC0-last
3. Reduction in total weight of mucus produced post viral inoculation, through last administration of IMP.
4. Relationship between various PK parameters (e.g., Cmax, Cmin, and AUC) and antiviral endpoints (e.g., viral load AUC, duration of shedding, symptom scores).
5. Change in total RSV-A symptoms after challenge until treatment cessation (using a composite of 10 self-reported symptoms on the symptom diary card).
6. Sequence analysis of the RSV polymerase region (amino acids 550-1100) of the RSV L protein.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Days 1-12 & follow up visit 1 & 2
2. Day 12
3. Days 1-12
4. PK parameters Day 12 & antiviral endpoints Day 2-12 & follow up visit 1 & 2
5. Day 1-12 & follow up visit 1
6. pre-dose, all 5 dosing days and thereafter until virus is no longer detectable

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Antiviral Activity
Tolerability

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 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.1.1.1

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)

Only healthy volunteers are being used for this study. There is no ongoing care post follow up.

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

2013-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-06-25

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