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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 10 December 2019
Main ID:  EUCTR2016-003038-26-DE
Date of registration: 08/12/2016
Prospective Registration: Yes
Primary sponsor: Argenx BVBA
Public title: A Study of the safety and effectiveness of ARGX-113 in Patients with Primary Immune Thrombocytopenia
Scientific title: 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
Date of first enrolment: 27/04/2017
Target sample size: 36
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003038-26
Study type:  Interventional clinical trial of medicinal product
Study design: 
Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: no
Cross over: no
Other: yes
Other trial design description: open label treatment after main study
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
Number of treatment arms in the trial: 3
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Austria Belgium Czech Republic France Germany Hungary Poland Spain
Ukraine United Kingdom
Contacts
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7, Building C B-9052 Zwijnaarde Belgium
Telephone: +3293103400
Email: regulatory@argenx.com
Affiliation:  Argenx BVBA
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7, Building C B-9052 Zwijnaarde Belgium
Telephone: +3293103400
Email: regulatory@argenx.com
Affiliation:  Argenx BVBA
Key inclusion & exclusion criteria
Inclusion criteria:
Main study
1. Ability to understand the requirements of the study, and comply
withthe 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

Exclusion criteria:
1. Use of anticoagulants, or any drug with antiplatelet effect (e.g., acetylsalicylic acid [aspirin] or other salicylate containing medications, cyclooxygenase inhibitors, adenosine diphosphate (ADP) receptor inhibitors, phosphodiesterase inhibitors, glycoprotein IIB/IIIA inhibitors, adenosine reuptake inhibitors, thromboxane inhibitors, antimalarials, and prostacyclins) 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.
4. Use of recombinant thrombopoietin at any time.
5. Use of rituximab within 6 months prior to Screening. Use of any anti-CD20 other than rituximab at any time is not permitted.
6. Use of corticosteroids which has not been stable for at least 4 weeks prior to Screening.
7. Use of immunosuppressants is not permitted within 4 weeks prior to Screening, with the exception of the following oral immunosuppressants: azathioprine [up to 2.5 mg/kg/day], danazol [up to 15 mg/kg/day], mycophenolate mofetil [up to 3 g/day], mycophenolate sodium [up to 2160 mg/day]) 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 given as below:
a. Aspartate aminotransferase (AST) or ALT > 3 × upper limit of normal (ULN).
b. Total serum bilirubin of > 1.5 x ULN (except for Grade 1 hyperbilirubinemia as defined by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], due solely to a documented medical diagnosis of Gilbert’s syndrome).
c. Serum creatinine of > 1.5 mg/dL or creatinine clearance < 50 mL/min (using Chronic Kidney Disease Epidemiology - Creatinine formula).
d. Hemoglobin = 9 g/dL.
e. Thyroid stimulating hormone or thyroglobulin outside of the central laboratory normal range.
f. International normalized ratio (INR) > 1.5 or activated partial thromboplastin time > 1.5 × ULN.
g. Total immunoglobulin G (IgG) level < 6 g/L.
h. Presence of > 1+ proteinuria
Note: A patient with isolated laboratory values that meet the thresholds listed above may be considered eligible. The agreed upon medical rationale, discussed between the investigator and sponsor, must be documented in the patient's chart prior to patient enrolment in the study
11. History of myeloproliferative or lymphoproliferative disorders at any time; or have a history of malignancy at any time unless deemed cured by adequate treatment with no evidence of recurrence for = 5 years prior to Screening. Patients with completely excised nonmelanoma skin cancers or cervical carcinoma in situ would be permitted at any time.
12. History of cerebrovascular accident or myocardial infarction within the last 12 months, before Screening, or current severe/unstable angina, ar


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Primary Immune Thrombocytopenia
MedDRA version: 20.1 Level: LLT Classification code 10074678 Term: Primary immune thrombocytopenic purpura System Organ Class: 100000004851
Therapeutic area: Body processes [G] - Immune system processes [G12]
Intervention(s)

Product Name: ARGX-113
Product Code: ARGX-113
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: N/A
CAS Number: 1821402-21-4
Current Sponsor code: ARGX-113
Other descriptive name: ARGX-113
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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

Primary end point(s): -Incidence and severity of 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.

Secondary Objective: 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 ARGX-113 (short term and long term) on:
??- platelet counts;
? - use of rescue treatment;
? - bleeding events.
- 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.To assess the PK of ARGX-113.
To assess the PD effects of ARGX-113.
To evaluate the immunogenicity of ARGX-113.
Timepoint(s) of evaluation of this end point: Various time points throughout the study
Secondary Outcome(s)

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,?z), 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
Timepoint(s) of evaluation of this end point: Various time points throughout the study
Secondary ID(s)
2016-003038-26-GB
ARGX-113-1603
Source(s) of Monetary Support
Argenx BVBA
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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