Clinical Trials Register

Summary
EudraCT Number:	2016-003038-26
Sponsor's Protocol Code Number:	ARGX-113-1603
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-12-14
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

Austria - BASG

A.2

EudraCT number

2016-003038-26

A.3

Full title of the trial

A Randomized, Double-blind, Placebo-controlled, Phase II Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of ARGX-113 in Patients with Primary Immune Thrombocytopenia

A.3.1

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

A Study of the safety and effectiveness of ARGX-113 in Patients with Primary Immune Thrombocytopenia

A.4.1

Sponsor's protocol code number

ARGX-113-1603

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	Argenx BVBA
B.1.3.4	Country	Belgium
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	Argenx BVBA
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Argenx BVBA
B.5.2	Functional name of contact point	Regulatory
B.5.3	Address:
B.5.3.1	Street Address	Industriepark Zwijnaarde 7, Building C
B.5.3.2	Town/ city	Zwijnaarde
B.5.3.3	Post code	B-9052
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+3293103400
B.5.5	Fax number	+3293103499
B.5.6	E-mail	regulatory@argenx.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	ARGX-113
D.3.2	Product code	ARGX-113
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	N/A
D.3.9.1	CAS number	1821402-21-4
D.3.9.2	Current sponsor code	ARGX-113
D.3.9.3	Other descriptive name	ARGX-113
D.3.9.4	EV Substance Code	SUB180001
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	20
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	Yes
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

Primary Immune Thrombocytopenia

E.1.1.1

Medical condition in easily understood language

Primary Immune Thrombocytopenia

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10074678
E.1.2	Term	Primary immune thrombocytopenic purpura
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of ARGX-113(short and long
term)
To evaluate the safety of repeated use of ARGX-113

E.2.2

Secondary objectives of the trial

To evaluate the patients with initial response i.e., platelet count ≥ 30 × 109/L and/or at least doubling of the Baseline count and absence of bleeding.
- To evaluate the clinical effect of ARGX-113 (short term and long term)
- platelet counts;
 - use of rescue treatment;
- bleeding events.
To assess the effect of ARGX-113 on quality of life.
To assess the PK of ARGX-113.
To assess the PD effects of ARGX-113.
To evaluate the immunogenicity of ARGX-113.
- To evaluate the efficacy of repeated use of ARGX-113.
- To assess the effect of ARGX-113 on quality of life.
- To assess the PK of ARGX-113.
- To assess the PD effects of ARGX-113.
- To evaluate the immunogenicity of ARGX-113.

Specifically for the extended FU period:
To assess the duration of the treatment effect for all patients who did
not relapse during the treatment period. This will be based on:
- local platelet counts;
- use of rescue treatment;
- bleeding events.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Main study
1. Ability to understand the requirements of the study, and comply with the study protocol procedures (including required study visits).
2. Male or female patients aged ≥ 18 to ≤ 85 years.
3. Eligible patients must receive standard-of-care treatment for ITP
following the ASH guidelines and International Working Group (IWG)
stable in dose and frequency for at least 4 weeks prior to Screening.
4. Confirmed diagnosis of ITP according to the American Society of
Hematology Criteria 2011 with (average) blood platelet counts < 30 ×
10E9/L and who have not experienced major bleeding in the last 4
weeks prior to Screening.
5. Women of childbearing potential must have a negative serum
pregnancy test at Screening and a negative urine pregnancy test at
Baseline prior to administration of IMP.
6. Female participants of childbearing potential must agree to use a
highly effective method of birth control (i.e., pregnancy rate of less than
1% per year) during the study and for 90 days after the discontinuation
of IMP.
7. Non-sterilized male patients who are sexually active with a female
partner of childbearing potential must use effective double contraception
Additional Inclusion Criteria for the Extended Follow-up Period
- Sign the amended ICF of the main study including its extended
followup
period
- Completed Visit 16 of the FU period of the protocol with a platelet
count ≥ 30 × 10E9/L and/or at least doubling of the Baseline platelet
count and absence of bleeding and remained on the same SoC
Eligibility criteria for the open-label treatment period (first treatment
cycle)
1. Please refer to inclusion criteria 5, 6 and 7 from the main study.
2. Provide written informed consent
3. Received at least 3 doses of the IMP and had at least 2 weeks of
follow-up in the main study.
4. Patient is at the same SoC as in the main study. Dose and/or
frequency increase is allowed, changing or stopping the SoC is not
allowed.
5. During up to 21 weeks of FU, the patient is relapsing i.e. platelet count
decreases to below 30 x 10E9/L or the patient's platelets never went up
to 30 x 10E9/L and are still below 30 x 10E9/L, and absence of bleeding.
Eligibility criteria for subsequent open-label retreatment cycles
The patient has the right to receive more than 1 retreatment cycle if:
1. Patient reached a platelet count of at least twice the platelet count
measured on the day of the first IMP administration during the previous
(re)treatment cycle, confirmed on at least 2 separate consecutive
occasions (at least 1 day apart but with maximum 7 days in between the
2 measurements), and measured during the treatment period up to
minimum 4 weeks of follow-up.
2. Patient received at least 3 doses of the IMP and had at least 4 weeks
follow-up in the previous treatment cycle.
3. Patient is at the same SoC as in the previous treatment cycle. Dose
and/or frequency increase is allowed, changing or stopping the SoC is
not allowed.
4. Patient is relapsing i.e. platelet count decreases to below 30 x 10E9/L
or the patient's platelets never went up to 30 x 10E9/L and are still
below 30 x 10E9/L, and absence of bleeding.

E.4

Principal exclusion criteria

1. Use of anticoagulants, or any drug with antiplatelet effect during the
study and within 3 weeks prior to Screening
2. Patients who have received any blood support or transfusion within 4
weeks prior to Screening
3. Use of IVIg or anti-D immunoglobulin treatment within 4 weeks prior
to Screening.
5. Use of rituximab within 6 months prior to Screening. other anti-CD20s
not permitted
6. Use of corticosteroids not been stable for at least 4 weeks prior to
Screening
7. Use of immunosuppressants not permitted within 4 weeks prior to
Screening except azathioprine, danazol, mycophenolate mofetil,
mycophenolate sodium which must have been stable for at least 4 weeks
prior to Screening
8. Use of any other biological therapy or investigational drug than those
previously indicated within 3 months or 5 half-lives of the drug
(whichever is longer) prior to Screening
9. Received vaccinations within 4 weeks prior to Screening or planned
during the study
10. At Screening, have clinically significant laboratory abnormalities
11. History of myeloproliferative or lymphoproliferative disorders at any
time; or history of malignancy at any time unless deemed cured
12. History of cerebrovascular accident or myocardial infarction within
the last 12 months, before Screening, or current severe/unstable angina,
arrhythmia, or at risk of ventricular arrhythmia, symptomatic congestive
heart failure
13. History of any thrombotic or embolic event within 12 months prior to
Screening
14. History of coagulopathy or hereditary thrombocytopenia or a family
history of thrombocytopenia
15. Known history or symptoms of systemic lupus erythematosus,
antiphospholipid antibody syndrome or any other clinically documented
auto-immune disease other than ITP
16. Prior history or symptoms suggestive of untreated Helicobacter
pylori infection
17. History of a recent major surgery
18. Active infection; a recent serious infection within the 8 weeks prior
to Screening.
19. Clinical evidence of significant unstable or uncontrolled acute or
chronic diseases other than ITP, uncontrolled diabetes
20. History of alcoholism or drug/chemical/substance abuse within the
past 2 years prior to Screening per investigator's opinion
21. Body Mass Index (BMI) at Screening ≥ 35 kg/m2
22. Female patient who is pregnant or lactating or have been lactating
within 3 months of Screening
Additional Exclusion Criterion for the Extended Follow-up Period
23. At the moment of start of extended FU period, being enrolled in a
clinical study with another investigational drug or device
Exclusion criteria for the open-label treatment period (first treatment
cycle)
1. At the moment of start of the open-label treatment period, being
enrolled in a clinical study with another investigational drug or device
2. Please refer to the following exclusion criteria from the main study: 1,
4, 19, 21, and 22
3. Use of IVIg or anti-D immunoglobulin treatment as rescue therapy at
any time during the main study or extended FU period
4. Received vaccinations within 4 weeks prior to any (re)treatment cycle
5. At Treatment Evaluation Visit, have clinically significant laboratory
abnormalities
6. Patient has a history of severe and/or serious hypersensitivity
reaction to IMP in ARGX- 113-1603 main study
Exclusion criteria for subsequent open-label retreatment cycles
1. Please refer to the exclusion criteria for the first treatment cycle of
the open-label treatment period
2. Patient has a history of severe and/or serious hypersensitivityreaction to IMP during the first treatment cycle of the open-label
treatment period

E.5 End points

E.5.1

Primary end point(s)

-Incidence and severity of treatment-emergent AEs (TEAEs) and serious AEs (SAEs).
- Changes from Baseline (mean, median, minimum and maximum values, shifts) in vital signs, electrocardiogram parameters (ECGs), physical examination abnormalities, and clinical laboratory assessments.

E.5.1.1

Timepoint(s) of evaluation of this end point

Various time points throughout the study

E.5.2

Secondary end point(s)

-Frequency and proportion of patients with initial response i.e., platelet count ≥ 30 × 109/L and/or at least doubling of the Baseline count and absence of bleeding at any time during the study.
- Mean change in platelet counts compared to Baseline.
-Frequency and proportion of patients with following response at any time during the study 5,1:
o Complete response (CR): Platelet count ≥ 100×109/L, confirmed on at least 2 separate consecutive occasions ≥ 7 days apart, and the absence of bleeding;
o Response (R): Platelet count ≥ 30 and < 100×109/L, and a greater than 2-fold increase in platelet count from Baseline, confirmed on at least 2 separate consecutive occasions ≥ 7 days apart, and the absence of bleeding;
o No response (NR): Platelet count < 30 × 109/L or less than doubling of the Baseline count or bleeding;
-Time to initial response: time from starting treatment to time to reach CR or R;
-Duration of response: time from the achievement of CR or R to loss of CR or R;
-Frequency and proportion of patients with response to ≥ 50×10E9/L: Platelet count increase to at least ≥ 50×10E9/L at any time during the study.
- Frequency and proportion of patients requiring rescue therapy.
-General bleeding assessment by the World Health Organization (WHO) bleeding scale and SMOG index of the ITP specific bleeding assessment tool (ITP-BAT)*.
- Change from Baseline in the Short Form-36 item Health Status Questionnaire (SF-36) and the Functional Assessment of Cancer Therapy (FACT-Th6)*.
- PK parameters of ARGX-113 including maximum observed concentration (Cmax), time of maximum concentration (tmax), plasma concentration prior to dosing (Ctrough), apparent terminal half-life (t1/2,λz), and accumulation ratio (Rac)*.
- Evaluation of pharmacodynamic markers: Total IgG, IgG isotypes** IgG1, IgG2, IgG3, IgG4; and antiplatelet antibody levels. In addition, IgA, IgD, IgE, and IgM will also be assessed**.
- Evaluate the incidence of antidrug antibodies (ADA) to ARGX-113*.

*not for the extended FU period (except WHO bleeding scale)
**IgG isotypes and IgA, IgA, IgE, IgM will not be assessed in the
openlabel
treatment period

E.5.2.1

Timepoint(s) of evaluation of this end point

Various time points throughout the study

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

long term efficacy.

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

Yes

E.8.1.7.1

Other trial design description

Open Label Behandlung nach der Hauptstudie

open label treatment after main study

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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)

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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. Subject will continue with routine care.

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

2017-02-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-04-09

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