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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: 25 November 2019
Main ID:  EUCTR2016-003038-26-ES
Date of registration: 27/12/2016
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: 07/02/2017
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: no
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: +34961245875
Email: regulatory@argenx.com
Affiliation:  Argenx BVBA
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7, Building C B-9052 Zwijnaarde Belgium
Telephone: +34961245875
Email: regulatory@argenx.com
Affiliation:  Argenx BVBA
Key inclusion & exclusion criteria
Inclusion criteria:
1. Ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), 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) that has been stable in dose and frequency for at least 4 weeks prior to Screening. Standard-of-care may include oral corticosteroids and/or permitted oral immunosuppressants and/or TPO-R agonist (see Section 7.9.2).
4. Confirmed diagnosis of ITP according to the American Society of Hematology Criteria 2010 with blood platelet counts < 30 × 109/L and who have not experienced major bleeding in the last 4 weeks prior to Screening.1 Note: The average platelet counts must be < 30 × 109/L with no single reading > 35 × 109/L as measured on 2 separate occasions at least 1 day apart during the 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.
Women of childbearing potential are defined as all female patients unless they are post-menopausal (defined by continuous amenorrhea) for at least 1 year with follicle-stimulating hormone (FSH) > 40 IU/L or are surgically sterile (i.e., women who had a hysterectomy, both ovaries surgically removed, or have current documented tubal ligation or any other permanent female sterilization procedure). Follicle-stimulating hormone can be used to confirm post-menopausal status in amenorrheic patients not on hormonal replacement therapy if the value is within the post-menopausal range per the central laboratory.
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.
Contraceptive methods that result in a low failure rate when used consistently and correctly include methods such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, and transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, and implantable), intrauterine devices (IUDs), intrauterine hormone-releasing system, true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant-periodic abstinence [e.g., calendar, ovulation] and withdrawal methods are not acceptable methods of contraception), bilateral tubal occlusion, or a male partner who has had a vasectomy with documented aspermia post procedure. All female participants using hormonal contraceptive, especially those using mycophenolate, must also use a barrier method (i.e., condom or occlusive cap [diaphragm or cervical/vault caps]) and should have been stable on their hormonal contraceptive treatment for at least 4 weeks prior to Screening.
7. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use effective double contraception, of which 1 method must be a barrier method and the other another barrier method or highly effective form of cont

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/L.
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
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, arrhythmia, or at risk of ventricular arrhythmia, symptomatic congestive heart failure (New York Heart Association Class III or IV), or uncontrolled hypertension (Grade 3 to 4 CTCAE). Uncontrolled hypertension is defined as a repeated elevation in the blood pressure exceeding 140 mmHg and over 90 mmHg despite appropr


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Primary Immune Thrombocytopenia
MedDRA version: 19.0 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)

Primary end point(s): -Incidence and severity of 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 on:
?- 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.
Main Objective: To evaluate the safety and tolerability 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 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 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;
-Response to = 50×109/L: Platelet count increase to at least = 50×109/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), 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.
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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