Clinical Trials Register

Summary
EudraCT Number:	2014-004341-27
Sponsor's Protocol Code Number:	MK-3641-008
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-02-08
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2014-004341-27

A.3

Full title of the trial

A Phase III, Randomized, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of MK-3641, a Ragweed (Ambrosia artemisiifolia) Sublingual Immunotherapy Tablet, in Children With a History of Ragweed-Induced Rhinoconjunctivitis With or Without Asthma

A.3.1

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

Ragweed Efficacy and Safety Pediatric Trial

A.3.2

Name or abbreviated title of the trial where available

Ragweed Efficacy and Safety Pediatric Trial

A.4.1

Sponsor's protocol code number

MK-3641-008

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/266/2016

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., 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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., 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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2	Functional name of contact point	Susan Lu
B.5.3	Address:
B.5.3.1	Street Address	One Merck Drive, P.O. Box 100
B.5.3.2	Town/ city	Whitehouse Station, NJ
B.5.3.3	Post code	08889-0100
B.5.3.4	Country	United States
B.5.4	Telephone number	+1732 594-5766
B.5.6	E-mail	susan_lu@merck.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	Yes
D.2.1.1.1	Trade name	RAGWIZAX
D.2.1.1.2	Name of the Marketing Authorisation holder	ALK-Abelló A/S
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	Sublingual tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Sublingual use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ambrosia artemisiifolia
D.3.9.2	Current sponsor code	MK-3641
D.3.9.3	Other descriptive name	Short Ragweed Pollen Allergenic Extract
D.3.9.4	EV Substance Code	SUB127622
D.3.10	Strength
D.3.10.1	Concentration unit	AgU antigen unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	12
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	No
D.3.11.8	Extractive medicinal product	Yes
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	Yes
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	Sublingual tablet
D.8.4	Route of administration of the placebo	Sublingual use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Rhinoconjunctivitis due to ragweed allergy

E.1.1.1

Medical condition in easily understood language

Ragweed allergic rhinitis

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10001726
E.1.2	Term	Allergic rhinitis due to pollen
E.1.2	System Organ Class	100000004870

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 efficacy of MK-3641 sublingual immunotherapy tablet (12 Amb a 1-U) versus placebo in the treatment of children 5 to 17 years of age with ragweed-induced rhinoconjunctivitis, with or without asthma, based on the Total Combined Score (TCS) [sum of rhinoconjunctivitis daily symptom score (DSS) and rhinoconjunctivitis daily medication score (DMS)] averaged over the peak ragweed season (RS)

E.2.2

Secondary objectives of the trial

To compare the following between the MK-3641 (12 Amb a 1 U) and placebo groups:
1.Average TCS during the entire RS ;
2.Average rhinoconjunctivitis DSS during the peak RS;
3.Average rhinoconjunctivitis DMS during the peak RS.

To assess the overall safety of MK-3641 (12 Amb a 1 U) in children 5 to 17 years of age with ragweed-induced rhinoconjunctivitis, with or without asthma.

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

Merck will conduct Future Biomedical Research on DNA (blood and/or saliva) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.

E.3

Principal inclusion criteria

In order to be eligible for participation in this trial, the subject must:
1.Have a legal representative who provides written informed consent for the trial on the subject’s behalf. The legal representative may also provide consent for Future Biomedical Research on the subject’s behalf. The subject, depending on their age and ability to understand the nature and intent of the study, must also assent to participate in the study main trial and to Future Biomedical Research.
2.Be ≥4 to ≤17 years of age on the day informed consent is obtained, however, the subject must be ≥5 years old at the Randomization Visit. The subject may be of either gender and any race/ethnicity.
3.Have a clinical history of significant ragweed pollen-induced allergic rhinitis/rhinoconjunctivitis of ≥1 year (at least 1 season for ages 4 to 6 years) or ≥2 years (at least 2 seasons for ages 7 to 17 years) duration diagnosed by a physician (with or without asthma) and have received treatment for the condition during the
previous ragweed season.
4.Have a positive skin prick test response to Ambrosia artemisiifolia at the Screening Visit.
5.Have a specific IgE against Ambrosia artemisiifolia ≥ IgE Class 2 (0.7 kU/L) at the Screening Visit.
6.Have a forced expiratory volume in 1 second (FEV1) ≥80% of predicted value at the Screening and Randomization Visits.
Note: A subject who is ≤7 years old and cannot perform reproducible FEV1 maneuvers, despite coaching, does not need to meet this criterion.
7.Be able to read, understand, and complete the questionnaires and diaries (or can have help from the parent/guardian).
8.If female, agree to remain abstinent or use (or have their partner use) an acceptable method of birth control.

Refer to protocol for complete list of inclusion criteria.

E.4

Principal exclusion criteria

The subject must be excluded from participating in the trial if the subject:
1.Has a clinical history of symptomatic seasonal allergic rhinitis (and/or asthma) due to another allergen, which has required regular medication during, or potentially overlapping, the ragweed season.
2.Has a clinical history of significant symptomatic perennial allergic rhinitis and/or asthma due to an allergen to which the subject is regularly exposed during the ragweed season which would interfere with assessment of the treatment effect.
3.Has any nasal condition that could confound the efficacy or safety assessments (e.g., nasal polyposis).
4.Has asthma requiring high daily doses of inhaled corticosteroids within the 6 months prior to the Screening Visit.
5.Is one of the following:
• >7 years old and cannot perform reproducible FEV1 maneuvers despite coaching;
• ≤7 years old who cannot perform reproducible FEV1 maneuvers despite coaching and has current symptoms of asthma characterized by recurrent episodes of wheezing, or episodes of cough, wheeze, difficulty in breathing, or chest tightness.
6.Has severe, unstable, or uncontrolled asthma, as judged by the clinical investigator, or has experienced a life-threatening asthma attack or an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalization due to asthma, or treatment with systemic corticosteroids (but allowing short-acting beta-agonists) at any time within the last 3 months prior to the Screening or Randomization Visits.
7.Has a history of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy, unknown cause, or inhalant allergen.
8.Has a diagnosis of eosinophilic esophagitis.
9.Has a history of chronic urticaria and/or chronic angioedema.
10.Has a clinical history of chronic sinusitis during the 2 years prior to the Screening or Randomization Visits.
11.Has current severe atopic dermatitis.
12.Has a history of allergy, hypersensitivity, or intolerance to the ingredients of the investigational medicinal products (except for Ambrosia artemisiifolia), rescue medications, or self-injectable epinephrine.
13.Has previously received MK-3641.
14.Is unable to meet medication washout requirements.

Refer to protocol for complete list of exclusion criteria.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study, the Total Combined Score (TCS), is a combination of (sum of) the rhinoconjunctivitis daily symptom score (DSS) and the rhinoconjunctivitis daily medication score (DMS) averaged over the peak ragweed season.

E.5.1.1

Timepoint(s) of evaluation of this end point

peak ragweed season

E.5.2

Secondary end point(s)

•Average Total Combined Score (TCS) during the Entire Ragweed Season (RS)
•Average rhinoconjunctivitis Daily Symptom Score (DSS) during the Peak Ragweed Season
•Average rhinoconjunctivitis Daily Medication Score (DMS) during the Peak Ragweed Season

E.5.2.1

Timepoint(s) of evaluation of this end point

•Entire Ragweed Season
•Peak Ragweed Season

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

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

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)

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

Yes

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Canada

Russian Federation

Serbia

Ukraine

United States

E.8.7

Trial has a data monitoring committee

Yes

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.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

1000

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

350

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

650

F.1.2

Adults (18-64 years)

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2019-02-08.

Yes

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.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

1000

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)

Once a subject has ended participation in the study, he/she will revert to usual care according to his/her own personal physician.

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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