A Study to Evaluate the Efficacy and Safety of Efgartigimod PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia

Study Overview
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Brief Summary
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This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group trial to evaluate the efficacy, safety, and effect on QoL/PRO of efgartigimod PH20 SC treatment in adult 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 the Safety of Efgartigimod (ARGX-113) PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia

Conditions
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Primary Immune Thrombocytopenia

Intervention / Treatment
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* Biological: Efgartigimod PH20 SC
* Other: Placebo PH20 SC


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Ability to understand the requirements of the trial and provide written informed consent, willing and able to comply with the trial protocol procedures Is at least the local age of consent for clinical studies when signing the ICF. Confirmed diagnosis of primary ITP made at least 3 months before randomization and based on the American Society of Hematology Criteria, and no known etiology for thrombocytopenia Diagnosis supported by a response to a prior ITP therapy (other than TPO-RAs), in the opinion of the investigator Mean platelet count of <30×10E9/L from at least 3 documented, qualifying counts within the 3 preceding months where at least 2 of the qualifying counts must be taken during the screening period: 1 platelet count collected during the screening period and the predose platelet count on the day of randomization (visit 1). If the third count is not available from the 3 preceding months, this third platelet count can be obtained during the screening period. A documented history of a platelet count of <30×10E9/L before screening At the start of the trial, the participant either takes concurrent ITP treatment(s) and has received at least 1 prior therapy for ITP in the past, or the participant does not take treatment for ITP (see note) but has received at least 2 prior treatments for ITP. Participants receiving permitted concurrent ITP treatment(s) at baseline must have been stable in dose and frequency for at least 4 weeks before randomization. Permitted concurrent ITP medications include corticosteroids, danazol, vinca alkaloids, oral immunosuppressants, dapsone, fostamatinib, and/or oral TPO-RAs. -Agree to use contraceptive measures consistent with local regulations and the protocol Exclusion criteria: Secondary ITP/thrombocytopenia associated with another condition, eg, lymphoma, chronic lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune thrombocytopenia, thrombocytopenia associated with myeloid dysplasia, or hematopoietic stem cell transplant 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, SC, or intramuscular route) or plasmapheresis (PLEX) within 4 weeks prior to randomization Use of romiplostim within 4 weeks prior to randomization Undergone splenectomy less than 4 weeks prior to randomization Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP Use of any monoclonal antibody or Fc fusion proteins, other than those previously indicated, within 6 months before the first dose of the IMP (eg, anti-CD20) At the screening visit, clinically significant laboratory abnormalities as follows: Hemoglobin ≤9 g/dL - OR - International normalized ratio >1.5 or activated partial thromboplastin time >1.5×upper limit of normal - OR - total IgG level <6 g/L History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of IMP. Participants with the following cancer can be included at any time: Adequately treated basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast or Incidental histological finding of prostate cancer (TNM stage T1a or T1b) 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, deep venous thrombosis, or pulmonary embolism) within 5 years prior to randomization History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia Evidence of an active clinically significant bleeding of an organ or internal mucosal bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic procedure based on the investigator's judgment (eg, intracranial hemorrhage, pulmonary hemorrhage, bleeding with ongoing need for packed red blood cell transfusion) Estimated high risk of a clinically significant bleeding of an organ or internal mucosal bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic procedure according to the investigator's judgment Clinical evidence of other significant serious diseases, have had a recent major surgery, or who have any other condition in the opinion of the investigator, that could confound the results of the trial or put the participant at undue risk 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, 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 Known hypersensitivity reaction to efgartigimod, rHuPH20, or 1 of its excipients Previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP Pregnant or lactating or intends to become pregnant during the trial Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of ITP or put the participant at undue risk 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 participant at undue risk Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse Received a live/live-attenuated vaccine less than 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 PH20 SC<br>Patients receiving efgartigimod PH20 SC treatment | Biological: Efgartigimod PH20 SC<br>* Subcutaneous injection with efgartigimod PH20 SC<br>* Other names: ARGX-113 PH20 SC;|
| Placebo Comparator: Placebo PH20 SC<br>Patients receiving placebo PH20 SC treatment | Other: Placebo PH20 SC<br>* Subcutaneous injection with placebo PH20 SC<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 ≥50×10E9/L for at least 4 of the 6 visits between week 19 and week 24 of the trial |  | Up to 5 weeks (between week 19 -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 |  | Up to 24 weeks | 
| Proportion of patients in the overall population (chronic and persistent ITP) with a sustained platelet count response defined as achieving platelet counts of ≥50×10E9/L for at least 4 of the 6 visits between week 19 and week 24 |  | Up to 5 weeks (between week 19-24) | 
| Proportion of patients in the overall population achieving platelet counts of ≥50×10E9/L for at least 6 of the 8 visits between week 17 and 24 of the trial |  | Up to 7 weeks (between week 17-24) | 
| Proportion of patients in the overall population with overall platelet response defined as achieving a platelet count of ≥50×10E9/L on at least 4 occasions at any time during the 24-week treatment period |  | Up to 24 weeks | 
| Extent of disease control defined as the number of cumulative weeks until week 12 with platelet counts of ≥50×10E9/L in the overall population |  | Up to 12 weeks | 
| Proportion of patients in the overall population with overall platelet response defined as achieving a platelet count of ≥50×10E9/L on at least 4 occasions at any time until week 12 |  | Up to 12 weeks | 
| Mean change from baseline in platelet count at each visit in the overall population |  | Up to 35 weeks | 
| Time to response defined as the time to achieve 2 consecutive platelet counts of ≥50×10E9/L in the overall population |  | Up to 35 weeks | 
| The number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×10E9/L and ≥20×10E9/L above baseline in the overall population |  | Up to 24 weeks | 
| In patients with baseline platelet count of <15×10E9/L, the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×10E9/L and ≥20×10E9/L above baseline in the overall population |  | Up to 24 weeks | 
| Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population |  | Up to 35 weeks | 
| Severity of the World Health Organization (WHO)-classified bleeding events in the overall population |  | Up to 35 weeks | 
| Proportion of patients with an International Working Group (IWG) response |  | Up to 35 weeks | 
| Proportion of patients with an International Working Group (IWG) complete response |  | Up to 35 weeks | 
| Proportion of patients with an International Working Group (IWG) initial response |  | Up to 35 weeks | 
| Incidence and severity of AEs, AEs of special interest (AESIs), and SAEs in the overall population |  | Up to 35 weeks | 
| Vital sign measurement: blood pressure in the overall population |  | Up to 35 weeks | 
| ECG: PR, QT and QRS interval in the overall population |  | Up to 35 weeks | 
| Laboratory assessments: blood and urine analysis in the overall population |  | Up to 35 weeks | 
| Rate of receipt of rescue therapy (rescue per patient per month) in the overall population |  | Up to 35 weeks | 
| Proportion of patients for whom dose and/or frequency of concurrent ITP therapies have increased at week 12 or later in the overall population |  | Up to 23 weeks (between week 12-35) | 
| Change from baseline in PRO (Functional Assessment of Chronic Illness Therapy Fatigue Scale [FACIT-Fatigue] at planned visits in the overall population |  | Up to 24 weeks | 
| Change from baseline in PRO Functional Assessment of Cancer Therapy questionnaire-Th6 [Fact-Th6]) at planned visits in the overall population |  | Up to 24 weeks | 
| Change from baseline in PRO QoL (Short Form-36 [SF-36]) at planned visits in the overall population |  | Up to 24 weeks | 
| Incidence of antibodies to efgartigimod and/or rHuPH20 in the overall population |  | Up to 35 weeks | 
| Prevalence of antibodies to efgartigimod and/or rHuPH20 in the overall population |  | Up to 35 weeks | 
| Titers of antibodies to efgartigimod and/or rHuPH20 in the overall population |  | Up to 35 weeks | 
| Presence of neutralizing antibodies (NAb) against efgartigimod and/or rHuPH20, and titers of NAb against efgartigimod and/or rHuPH20 in the overall population |  | Up to 35 weeks | 
| Serum efgartigimod concentration observed predose (Ctrough) in the overall population |  | Up to 35 weeks | 
| Pharmacodynamics markers: total IgG and antiplatelet antibody levels in the overall population |  | Up to 35 weeks |