Clinical Trials Register

Summary
EudraCT Number:	2013-003096-35
Sponsor's Protocol Code Number:	WF10-C-2013/R-2-02
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-10-16
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

Germany - BfArM

A.2

EudraCT number

2013-003096-35

A.3

Full title of the trial

A multi-centre, randomised, placebo-controlled, double-blind, parallel-group study on the efficacy and safety of WF10 and its main constituents in patients with refractory allergic rhinitis

A.3.1

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

Investigation of the effects of novel medication and its constituents in patients with allergic rhinitis that is not responsive to conventional medication

A.4.1

Sponsor's protocol code number

WF10-C-2013/R-2-02

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	Nuvo Research GmbH
B.1.3.4	Country	Germany
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	NUVO Research GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ACPS - Network GmbH
B.5.2	Functional name of contact point	Trial coordinator
B.5.3	Address:
B.5.3.1	Street Address	11 Philippsring
B.5.3.2	Town/ city	Mainz-Kastel
B.5.3.3	Post code	55252
B.5.3.4	Country	Germany
B.5.4	Telephone number	00496134180467
B.5.5	Fax number	00496134180468
B.5.6	E-mail	c.demey@acps-network.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.3.1	Product name	WF10
D.3.4	Pharmaceutical form	Concentrate for 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	OXO-K993
D.3.9.1	CAS number	92047-76-2
D.3.9.3	Other descriptive name	TCDO
D.3.10	Strength
D.3.10.1	Concentration unit	mmol/l millimole(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	693
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.IMP: 2
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	NRI-1025
D.3.2	Product code	NRI-1025-01
D.3.4	Pharmaceutical form	Concentrate for 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	Sodium chlorite (WF10-analogue without chlorate and sulphate)
D.3.9.2	Current sponsor code	NRI-1025
D.3.9.3	Other descriptive name	Formulation code NRI-1025-01
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.425
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.IMP: 3
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	NRI-1026
D.3.2	Product code	NRI-1026-01
D.3.4	Pharmaceutical form	Concentrate for 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	Sodium chlorate (WF10-analogue without chlorite and sulphate)
D.3.9.2	Current sponsor code	NRI-1026
D.3.9.3	Other descriptive name	Formulation code NRI-1026-01
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.15
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	Concentrate for 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

refractory allergic rhinitis

E.1.1.1

Medical condition in easily understood language

allergic rhinitis not responsive to conventional medication

E.1.1.2

Therapeutic area

Diseases [C] - Ear, nose and throat diseases [C09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10001723
E.1.2	Term	Allergic rhinitis
E.1.2	System Organ Class	100000004855

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 describe and compare the efficacy, safety and tolerability of treatment with WF10 and its main constituents NRI-1025 ("chlorite") and NRI-1026 ("chlorate") relative to saline in patients with refractory allergic rhinitis.

E.2.2

Secondary objectives of the trial

To compare the efficacy, safety and tolerability of treatment with NRI-1025 and/or NRI-1026 with that of WF10.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects meeting all of the following conditions will be eligible for enrollment:
IN.1) Male and female outpatients (in female patients, see also item FEM.1-3 below)
IN.2) 18-70 years of age
IN.3) Body weight 45 – 110 kg (included)
IN.4) History of refractory rhinitis defined as persistence or recurrence of symptomatic episodes in spite of conventional treatment over the last one year before the screening (SCR) visit
IN.5) Positive allergen skin test to the relevant allergen(s) within the last two years before SCR
IN.6) Total nasal symptom score TNSS (see Section 6.1.1) ≥ 6 (/12) (at the baseline visit [BL])
IN.7) ± controlled bronchial asthma provided it is stable and is not treated with more than low-to-medium dose inhaled corticosteroids
IN.8) Ability to read and understand German well enough to answer the scoring questions (TNSS, TOSS) and the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) without translation or explanation
IN.9) Willing and able to provide informed consent

In order to be eligible, female patients also need to comply with all of the following criteria:
FEM.1) Non-pregnant
FEM.2) Non-lactating
FEM.3) Non-childbearing potential, while
o Surgically sterile
o OR post-menopausal for at least 6 months prior to the screening (SCR) visit
o OR having a negative pregnancy test at SCR and using a method of contraception with a low failure rate (PEARL Index) (i.e. less than 1% per year) when used consistently and correctly (including oral contraceptives, hormone implant, intrauterine device, male sexual partner(s) surgically sterile, abstinence)

E.4

Principal exclusion criteria

Subjects meeting any of the following criteria will be excluded from enrollment:

EX.2) Previous participation in the trial
EX.3) Participant in any other trial during the last 30 days
EX.4) Previous treatment with WF10 within the last two years
EX.5) Non-allergic rhinitis, rhinitis medicamentosa, idiopathic rhinitis or sinusitis; nasal surgery within the last 6 months before SCR; presence of a severely deviated septum, septal perforation, structural nasal defect or large nasal polyps causing obstruction
EX.6) Uncontrolled bronchial asthma
EX.7) Any co-morbidity (or sign thereof) which might put the patient at undue risk or might confound the evaluation of the trial criteria (as based on the Investigator's evaluation of the screening data incl. ECG) in particular, but not limited to: relevant haematological, cardiovascular, hepatic, renal, neurological or psychiatric disease
EX.8) Clinical laboratory tests outside of the normal range to an extent that is to be considered clinically relevant including, but not limited to: liver enzymes > 3 times the upper limit of the normal range; haemoglobin lower than 110% of the lower limit of the gender specific normal laboratory range
EX.9) Glucose-6-phosphate dehydrogenase (G6PD) deficiency ≤ class III i.e. ≤ 60% activity
EX.10) Sickle-cell anaemia
EX.11) Present or recent treatment with prohibited medication (see Section 5.9)
EX.12) Patients with a completed series of anti-allergy immunotherapy concluded within the past year or who are still receiving such therapy
EX.13) Patients with unsuitable veins
EX.14) Planned travel outside the study region during the first month of the trial
EX.15) Patients unwilling or unable to keep the diary (as evaluated at BL)
EX.16) Patients with a baseline use (between SCR- and BL-visit) of rescue medication that is to be considered exaggerated and/or that reflects inadequate handling of the rescue medication (as evaluated at BL)

E.5 End points

E.5.1

Primary end point(s)

Total nasal symptom score (TNSS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Third week after the start of a five-day treatment cycle of daily infusions of the IMP

E.5.2

Secondary end point(s)

Efficacy:
- Total ocular symptom score (TOSS)
- Composite TNOSS (= TNSS + TOSS)
- Single symptoms of TNSS and TOSS
- Use of rescue medication (desloratidine 5 mg tablets as provided)
- MiniRQLQ
- Patients' overall evaluation of efficacy
- Investigators' overall evaluation of efficacy

Safety and tolerability:
- wellbeing and adverse events
- physical examination (and on-study changes thereof)
- clinical laboratory safety tests (haematology, clinical chemistry, urinalysis)
- vital function
- 12-lead ECG
- Spirometry
- Patients' overall evaluation of tolerability
- Investigators' overall evaluation of tolerability

Optional criteria (at selected sites only):
- At selected sites: whole-body-plethysmography
- At selected sites: exhaled NO (eNO)

E.5.2.1

Timepoint(s) of evaluation of this end point

Safety and tolerability to be evaluated on the infusion days and three, six, nine, twelve, and sixteen weeks after the start of the five-day medication cycle.
Secondary efficacy criteria to be evaluated three, six, nine, twelve, and sixteen weeks after the start of the five-day medication cycle.

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

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

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Proof-of-concept study with composite solution relative to constituents administered separately

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

proof-of-concept

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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

EOS = visit W16 (week 16). If unresolved safety findings at W16, FU is needed until they have satisfactorily subsided or have stabilised to a sufficient extent (no further marked improvement to be expected) - < 1 month for AE, < 3 months for SAE.
Voluntary, unblinded, non-interventional, observational follow-up is organised at 6, 12, 18 and 24 months after the first day of infusion for those participants who are willing, able, and consenting to attend such non-technical visit (interview only)

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:

140

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

184

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)

normal treatment of persistent allergic rhinitis

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

2013-12-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-01-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-02-15

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