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

• Register: EUCTR
• Last refreshed on: 27 July 2020
• Main ID: EUCTR2016-003038-26-GB
• Date of registration: 16/11/2016
• 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, followed by an Open-Label Treatment Period - ARGX-113-1603_Argenx BVBA
• Date of first enrolment: 08/02/2017
• 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: 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
• Affiliation: Argenx BVBA

• Name: Regulatory
• Affiliation: Argenx BVBA

Key inclusion & exclusion criteria

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 follow-up 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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

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
4. Use of recombinant thrombopoietin
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 histor

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Immune system processes [G12]

Primary Immune Thrombocytopenia
MedDRA version: 20.1 Level: LLT Classification code 10074678 Term: Primary immune thrombocytopenic purpura System Organ Class: 100000004851

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 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 × 10E9/L and/or at least doubling of the Baseline platelet count and absence of bleeding.
- To evaluate the clinical effect of 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.

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

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 × 10E9/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:
o Complete response (CR): Platelet count = 100×10E9/L, confirmed on at least 2 separate consecutive occasions = 7 days apart, and the absence of bleeding;
o Response (R): Platelet count = 30 and < 100×10E9/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 × 10E9/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 open-label treatment period

Timepoint(s) of evaluation of this end point: Various time points throughout the study

Secondary ID(s)

ARGX-113-1603

Source(s) of Monetary Support

Argenx BVBA

Ethics review

Status: Approved
Approval date: 08/02/2017
Contact:

Results

• Results available: Yes
• Date Posted: 03/05/2020
• Date Completed: 09/04/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-003038-26/results