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

JRCT ID: jRCT2071210025

Registered date:24/05/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Primary Immune Thrombocytopenia
• Date of first enrollment: 20/08/2021
• Target sample size: 9
• Countries of recruitment: Argentina,Japan,Australia,Japan,Bulgaria,Japan,Chile,Japan,China,Japan,Colombia,Japan,Denmark,Japan,France,Japan,Georgia,Japan,Germany,Japan,Greece,Japan,Ireland,Japan,Israel,Japan,Italy,Japan,Jordan,Japan,Korea,Japan,Republic of Latvia,Japan,Mexico,Japan,New Zealand,Japan,Norway,Japan,Peru,Japan,Poland,Japan,Portugal,Japan,Romania,Japan,Russian Federation,Japan,Serbia,Japan,South Africa,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan
• Study type: Interventional
• Intervention(s): Patients will receive ARGX-113 PH20 SC (1000 mg of Efgartigimod Alfa) or placebo PH20 SC, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or biweekly, adjusted according to their platelet count. From visits 17 to 24, patients will be fixed on the dosing schedule they were receiving at visit 16 or the last visit at which IMP was administered (i.e. either weekly or biweekly).

Outcome(s)

• Primary Outcome: Proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet counts of >=50*10^9/L for at least 4 of the 6 visits between week 19 and week 24 of the trial.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Participants are eligible to be included in the trial only if all of the following criteria apply:
1. Ability to understand the requirements of the trial and provide written informed consent (including consent for the use and disclosure of research-related health information), willing and able to comply with the trial protocol procedures (including attending the required trial visits)
2. Male or female, aged >=18 years at the time the informed consent form (ICF) is signed
3. 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
4. Diagnosis supported by a response to a prior ITP therapy (other than TPO-RAs), in the opinion of the investigator
5. Mean platelet count of <30*10^9/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.
6. A documented history of a platelet count of <30*10^9/L before screening
7. 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.
Note: Participants not receiving concurrent ITP therapy are also eligible for the trial if they have not received prior ITP therapy for at least 4 weeks before baseline, and 6 months in case of prior ITP therapy with an anti-CD20 therapy (eg, rituximab).
8. Agree to use contraceptive measures consistent with local regulations and the following:
Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving IMP.
9. Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use an acceptable method of contraception, ie, a condom from signing the ICF through the last administration of the IMP. Male participants are also not allowed to donate sperm during this time.
10. For Japanese participants enrolled in sites in Japan only: A Japanese participant is defined as a participant whose parents and 4 grandparents are Japanese, who has the Japanese nationality, was born in Japan, has not lived outside of Japan for a total of >10 years, and currently lives in Japan.

Exclude criteria

Participants are excluded from the trial if any of the following criteria apply:
1. 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
2. Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) within 4 weeks prior to randomization
3. Use of any transfusions within 4 weeks prior to randomization
4. Use of Ig (IV, SC, or intramuscular route) or plasmapheresis (PLEX) within 4 weeks prior to randomization
5. Use of romiplostim within 4 weeks prior to randomization
6. Undergone splenectomy less than 4 weeks prior to randomization
7. Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP
8. 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)
9. 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
10. 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:
a. Adequately treated basal cell or squamous cell skin cancer
b. Carcinoma in situ of the cervix
c. Carcinoma in situ of the breast or
d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
11. Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments
12. History of any major thrombotic or embolic event (eg, myocardial infarction, stroke, deep venous thrombosis, or pulmonary embolism) within 5 years prior to randomization
13. History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia
14. 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 judgment of Investigator (eg, intracranial hemorrhage, pulmonary hemorrhage, bleeding with ongoing need for packed red blood cell transfusion)
15. 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 judgment of Investigator
16. 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
17. Positive serum test at screening for an active viral infection with any of the following conditions:
a. 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)
b. Hepatitis C virus (HCV) based on HCV-antibody assay (unless associated with a negative HCV RNA test)
c. 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/mm^3
18. Known hypersensitivity reaction to efgartigimod, rHuPH20, or 1 of its excipients
19. Previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP
20. Pregnant or lactating or intends to become pregnant during the trial
21. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening
22. 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
23. 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
24. Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse
25. 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.
26. For participants enrolled in sites in Japan only: positive Helicobacter pylori test at the screening visit.

Related Information

• Primary Sponsor: Gandini Domenica
• Secondary ID(s): 2020-004032-21,NCT04687072