E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Immune Thrombocytopenia |
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E.1.1.1 | Medical condition in easily understood language |
Primary Immune Thrombocytopenia |
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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 |
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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 |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
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 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. |
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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 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 history of severe and/or serious hypersensitivity reaction to IMP during the first treatment cycle of the open-label treatment period |
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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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Various time points throughout the study
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E.5.2 | 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,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 open-label treatment period |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various time points throughout the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
open label treatment after main study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |