Clinical Trials Register

Summary
EudraCT Number:	2022-003004-33
Sponsor's Protocol Code Number:	AR-DEX-22-01
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2023-02-01
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2022-003004-33

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, parallel group study to assess the efficacy, safety, and tolerability of dexpramipexole administered orally for 52 weeks in participants with severe eosinophilic asthma

A.3.1

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

Assess the efficacy, safety, & tolerability of oral dexpramipexole in severe eosinophilic asthma

A.3.2

Name or abbreviated title of the trial where available

EXHALE-2

A.4.1

Sponsor's protocol code number

AR-DEX-22-01

A.5.4

Other Identifiers

Name:

IND

Number:

122746

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/09/2022

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Areteia Therapeutics, 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	Areteia Therapeutics, 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	Areteia Therapeutics, Inc.
B.5.2	Functional name of contact point	Andrew Friedman
B.5.3	Address:
B.5.3.1	Street Address	101 Glen Lennox Drive Suite 300
B.5.3.2	Town/ city	Chapel Hill
B.5.3.3	Post code	NC 27517
B.5.3.4	Country	United States
B.5.4	Telephone number	+16099550467
B.5.6	E-mail	andrew.friedman@populationhp.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	Dexpramipexole 75mg
D.3.2	Product code	KNS-760704
D.3.4	Pharmaceutical form	Film-coated tablet
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	Dexpramipexole
D.3.9.1	CAS number	908244-04-2
D.3.9.2	Current sponsor code	KNS-760704
D.3.9.3	Other descriptive name	Dexpramipexole dihydrochloride monohydrate
D.3.9.4	EV Substance Code	SUB188285
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
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	Dexpramipexole 150mg
D.3.2	Product code	KNS-760704
D.3.4	Pharmaceutical form	Film-coated tablet
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	Dexpramipexole
D.3.9.1	CAS number	908244-04-2
D.3.9.2	Current sponsor code	KNS-760704
D.3.9.3	Other descriptive name	Dexpramipexole dihydrochloride monohydrate
D.3.9.4	EV Substance Code	SUB188285
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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	Film-coated tablet
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

Severe Eosinophilic Asthma

E.1.1.1

Medical condition in easily understood language

Severe Asthma

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10068462
E.1.2	Term	Eosinophilic asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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 demonstrate the efficacy of dexpramipexole in reducing severe asthma exacerbations.

E.2.2

Secondary objectives of the trial

• To demonstrate the efficacy of dexpramipexole on pulmonary function.
• To demonstrate the efficacy of dexpramipexole on asthma control and quality of life
• To evaluate the effect of dexpramipexole on blood eosinophils.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Signed informed consent form and assent form, as appropriate.
2.Male or female ≥12 years of age at Screening Visit 1.
a. Participants in Poland must be ≥18 years of age at Screening Visit 1.
3. Documented physician diagnosis of asthma for ≥12 months prior to
Screening Visit 1.
4.Treatment of asthma, participants must satisfy all the below (items a
to c):
a.Participants who have received asthma controller medication with
medium or high dose inhaled corticosteroids on a regular basis for at least 12 months
prior to Screening Visit 1.
b.Documented treatment with a stable dose
for at least 3 months prior to Screening Visit 1.
c.Use of one of more additional daily maintenance asthma controller.
5.Pre-BD FEV1 ≥40% and <80% (<90% for participants 12 to 17 years of
age) of predicted at Screening Visit 2.
6.Variable airflow obstruction documented.
7.ACQ-6 ≥1.5 at Screening Visit 2.
8.Documented history of at least two asthma exacerbations requiring
treatment with systemic corticosteroids within the past 12-month period prior to Screening Visit 1.
9.Negative urine pregnancy test for women of childbearing potential
(WOCBP; after menarche) at the Screening Visit 2 and Baseline Visit.
10.WOCBP must use birth control from Screening Visit 1 through the End of Study Visit.

E.4

Principal exclusion criteria

1.A participant who experiences a severe asthma exacerbation
at any time from 4 weeks prior to the Screening Visit 1 up
to and including the Baseline Visit.
2.Current diagnosis of diseases which may confound interpretation of
this study's findings such as allergic bronchopulmonary aspergillosis,
eosinophilic granulomatosis with polyangiitis, eosinophilic
gastrointestinal diseases, hypereosinophilic syndrome, chronic
obstructive pulmonary disease, idiopathic pulmonary fibrosis.
3.Respiratory infection: Upper or lower respiratory tract, sinus, or middle
ear infection within the 4 weeks before Screening Visit 1.
4.For participants aged 12 to 17 years old, AEC of <0.15x10ˆ9/L at
Screening Visit 1. Not applicable in Poland where all participants are at least 18
years of age.
5.Treatment with a biologic investigational drug in the last 5 months prior
to Screening Visit 1. Treatment with non-biologic investigational drugs in the previous 30
days or five-half-lives prior to Screening Visit 1, whichever is longer. Treatment with GSK3511294
(long-acting anti-IL-5) in the past 12 months.
6.Treatment with any of the following monoclonal antibody therapies
within 120 days prior to Baseline Visit: benralizumab, dupilumab,
mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
7.Treatment with pramipexole (Mirapex®) within 30 days of Baseline Visit.
8.Treatment with selected drugs known to have a substantial risk of
neutropenia in the past 30 days prior to Screening Visit 1.
9.Bronchial thermoplasty procedure in the past 12 months prior to Screening
Visit 1 or planned during the coming year.
10.Weight <40 kg at Screening Visit 2.
11.Current smoking within 12 months prior to Screening Visit 1 or a smoking history of >10
pack-years.
12.Known or suspected alcohol or drug abuse
13.Uncontrolled severe hypertension prior to he Baseline
Visi despite anti-hypertensive therapy.
14.History of malignancy that required surgery (excluding local and
wide-local excision), radiation therapy and/or systemic therapy during
the 5 years prior to the Baseline Visit.
15.History of human immunodeficiency virus (HIV) infection or chronic
infection with hepatitis B or C.
16.A helminth parasitic infection diagnosed within 24 weeks prior to Screening Visit 1
that has not been treated with or has failed to respond to standard of care (SoC) therapy.
17.Medical or other condition likely to interfere with participant's ability
to undergo study procedures, adhere to visit schedule, or comply with
study requirements.
18.Known or suspected noncompliance with medication.
19.Unwillingness or inability to follow the procedures outlined in the
protocol.
20.Absolute neutrophil count <2.000x10ˆ9/L at Screening Visit 1 or Screening
Visit 2.
21.Renal dysfunction.
22.Active liver disease.
23.History of New York Heart Association class IV heart failure or last
known left ventricular ejection fraction <25%.
24.History of major adverse cardiovascular event (MACE) within 3
months prior to the Baseline Visit.
25.History of cardiac arrhythmia within 3 months prior to the Baseline Visit that is
not controlled by medication or via ablation.
26.History of long QT syndrome.
27.Corrected QT interval by Fridericia (QTcF) interval >450 ms for males
and >470 ms for females at Screening Visit 2 or QTcF ≥480 ms for participants
with bundle branch block.
28.Clinically important abnormalities in resting ECG that may interfere
with the interpretation of QTcF interval.
29.Pregnant women or women breastfeeding.
30.Males who are unwilling to use an acceptable method of birth control
during the entire study period (ie, condom with spermicide).

E.5 End points

E.5.1

Primary end point(s)

•Annualized rate of severe asthma exacerbations (AAER) over 52 weeks.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52

E.5.2

Secondary end point(s)

•Pre-BD FEV1, absolute change from baseline, averaged across visits at Weeks 36, 44, and 52.
•Asthma Control Questionnaire-6 (ACQ-6), change from baseline, averaged across visits at Weeks 36, 44, and 52.
•Standardized version of the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) change from baseline to Week 52.

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to the clinical study Protocol

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)

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

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

Argentina

Colombia

North Macedonia

Brazil

Georgia

Korea, Republic of

Mexico

Serbia

United Kingdom

United States

Bulgaria

Poland

Romania

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.8.9.1

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

1115

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

210

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

270

F.4.2.2

In the whole clinical trial

1395

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)

After the study completion subjects will continue the treatment of care as per decision of their doctor

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

2023-07-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-01-18

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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