A Study to Assess the Efficacy and Safety of Efgartigimod in Adult Patients With Primary Immune Thrombocytopenia (ITP).

Study Overview
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Brief Summary
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This is a randomized, double-blind placebo-controlled multicenter phase 3 trial to evaluate the efficacy and safety of ARGX-113 in patients with primary ITP.

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Efgartigimod (ARGX 113) 10 mg/kg Intravenous in Adult Patients With Primary Immune Thrombocytopenia (ITP)

Conditions
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Primary Immune Thrombocytopenia

Intervention / Treatment
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* Biological: efgartigimod
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Ability to understand the requirements of the trial, to provide written informed consent (including consent for the use and disclosure of research-related health information), and to comply with the trial protocol procedures (including required trial visits). Male or female patient aged ≥18 years. Confirmed ITP diagnosis, at least 3 months before randomization and according to the American Society of Hematology Criteria, and no known other etiology for thrombocytopenia. Diagnosis supported by a response to a prior ITP therapy (other than thrombopoietin receptor agonists [TPO-RAs]), in the opinion of the investigator. Mean platelet count of <30×10E9/L from 2 counts: 1 platelet count collected during the screening period and the predose platelet count on the day of randomization (visit 1). At the start of the trial, the patient is either on concurrent ITP treatment(s) and has received at least 1 prior therapy for ITP in the past, or the patient is not on treatment for ITP but has received at least 2 prior treatments for ITP. Patients receiving permitted concurrent ITP treatment(s) at baseline, must have been stable in dose and frequency for at least 4 weeks prior to randomization. Permitted concurrent ITP medications include oral corticosteroids, oral immunosuppressants, dapsone/danazol, fostamatinib, and/or oral TPO-RAs. Patients not receiving concurrent ITP therapy are also eligible for the trial if they have not received prior ITP therapy for at least 4 weeks prior to baseline, and 6 months in case of prior ITP therapy with an anti-CD20 therapy (eg, rituximab). Women of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline before trial medication (infusion) can be administered. Women are considered of childbearing potential unless they are postmenopausal (defined by continuous amenorrhea) for at least 1 year with a folliclestimulating hormone (FSH) of >40 IU/L or are surgically sterilized (ie, women who had a hysterectomy, a bilateral salpingectomy, both ovaries surgically removed, or have a documented permanent female sterilization procedure including tubal ligation). Folliclestimulating hormone can be used to confirm postmenopausal status in amenorrheic patients not on hormonal replacement therapy. Women of childbearing potential should use a highly effective or acceptable method of contraception during the trial and for 90 days after the last administration of the IMP. They must be on a stable regimen, for at least 1 month: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation oral intravaginal transdermal progestogen-only hormonal contraception associated with inhibition of ovulation: oral injectable implantable intrauterine device (IUD) intrauterine hormone-releasing system bilateral tubal occlusion vasectomized partner (provided that the partner is the sole sexual partner of the trial participant and documented aspermia post procedure) continuous abstinence from heterosexual sexual contact. Sexual abstinence is only allowable if it is the preferred and usual lifestyle of the patient. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not acceptable male or female condom with or without spermicide cap, diaphragm, or sponge with spermicide -Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use an acceptable method of contraception, ie, a condom. Male patients practicing true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) can be included. Sterilized male patients who have had a vasectomy with documented aspermia post procedure can be included. In addition, male patients are not allowed to donate sperm during this period from signing of ICF, throughout the duration of the trial, and for 90 days after the last administration of IMP. Exclusion criteria: ITP/thrombocytopenia associated with another condition, eg, lymphoma, chronic lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune thrombocytopenia, or thrombocytopenia associated with myeloid dysplasia. Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) within 4 weeks prior to randomization. Use of any transfusions within 4 weeks prior to randomization. Use of Ig (IV, subcutaneous, or intramuscular route) or plasmapheresis (PLEX), 4 weeks prior to randomization. Use of anti-CD20 therapy (eg, rituximab) within 6 months prior to randomization. Use of romiplostim within 4 weeks prior to randomization. Undergone splenectomy less than 4 weeks prior to randomization. Use of any other investigational drug within 3 months or 5 half lives of the drug (whichever is longer) prior to randomization. Use of monoclonal antibodies or crystallized fragment (Fc) fusion proteins, other than those previously indicated, within 3 months prior to randomization. At the screening visit, clinically significant laboratory abnormalities as below: o Hemoglobin ≤9 g/dL. OR - o International normalized ratio >1.5 or activated partial thromboplastin time >1.5×ULN. OR - o Total IgG level <6 g/L. Patients who have a history of malignancy, including malignant thymoma, or myeloproliferative or lymphoproliferative disorders, unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before screening. Patients with completely excised non-melanoma skin cancer (such as basal cell carcinoma or squamous cell carcinoma) or cervical carcinoma in situ would be permitted at any time. Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments. History of any major thrombotic or embolic event (eg, myocardial infarction, stroke, pulmonary embolism, deep venous thrombosis) within 12 months prior to randomization. History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia. History of a recent or planned major surgery (that involves major organs eg, brain, heart, lung, liver, bladder, or gastrointestinal tract) within 4 weeks of randomization. Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless associated with a negative HBV DNA test (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf) Hepatitis C virus (HCV) based on HCV-antibody assay (unless associated with a negative HCV RNA test) Human immunodeficiency virus (HIV) based on test results that are associated with an acquired immunodeficiency syndrome (AIDS)-defining condition or a CD4 count ≤200 cells/mm3 Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than ITP (eg, cardiovascular, pulmonary, hematologic, gastrointestinal, endocrine, hepatic, renal, neurological, malignancy, infectious diseases, uncontrolled diabetes) despite appropriate treatments which could put the patient at undue risk. Patients with known medical history of hypersensitivity to any of the ingredients of the IMP. Patients who previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP. Pregnant or lactating females. Employees of the investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial center, as well as family of the employees or the investigator. Patients who received a live/live-attenuated vaccine within 4 weeks before screening. The receipt of any inactivated, sub-unit, polysaccharide, or conjugate vaccine at any time before screening is not considered an exclusion criterion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: efgartigimod<br>Patient receiving efgartigimod | Biological: efgartigimod<br>* Intravenous infusion of efgartigimod<br>* Other names: ARGX-113;|
| Placebo Comparator: Placebo<br>Patients receiving placebo | Other: Placebo<br>* Intravenous infusion of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet counts of at least 50×10E9/L for at least 4 of the 6 visits between week 19 and 24 of the trial. | Proportion of subjects with chronic ITP with a sustained platelet count response was defined as achieving platelet counts of at least 50 × 10^9 per litre for at least 4 of the 6 visits between weeks 19 and 24 of the study. | Up to five weeks (between visits 19 and 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of disease control defined as the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥50×10E9/L in the chronic ITP population | Extent of disease control, defined as the cumulative number of weeks over the planned 24-week treatment period with platelet counts of ≥50 × 10^9/L in the chronic ITP population. | Up to 24 weeks (treatment period) | 
| Proportion of patients in the overall population (chronic and persistent ITP) with a sustained platelet count response defined as achieving platelet counts of at least 50×10E9/L for at least 4 of the 6 visits between week 19 and 24 of the trial | Proportion of subjects in the overall population achieving platelet counts of at least 50 × 10^9/L for at least 6 of the 8 visits between weeks 17 and 24 of the study. | Up to five weeks (between visits 19 and 24) | 
| Incidence and severity of the WHO-classified bleeding events | Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population. Analysis was performed on Full Analysis Set population that included all randomized subjects. This secondary endpoint used the WHO-classified bleeding scale. Bleeding was the predominant clinical manifestation of ITP and was typically related to platelet count. Accordingly, measuring bleeding was important for monitoring this subject population. The WHO bleeding scale was neither specific to nor validated for ITP, but had been implemented in ITP clinical studies; no specific and validated tools for assessing bleeding in ITP were available. | Up to 24 weeks (From Week 1 to Week 24) | 
| Proportion of patients in the overall population achieving platelet counts of at least 50 x 10^9/L for at least 6 of the 8 visits between week 17 and 24 of the trial. | Proportion of subjects in the overall population (chronic and persistent ITP) with a sustained platelet count response, defined as achieving platelet counts of at least 50 × 10^9/L for at least 4 of the 6 visits between weeks 19 and 24 of the study. The analysis was performed on Full Analysis set population that included all randomized subjects in the study. | Up to 7 weeks (between visits 17 and 24) |