D69 NULL NULL
Conditions
Interventions
The total maximum trial duration per participant is up to 35 weeks:
- Up to 2 weeks of screening
- 24 weeks treatment period
- End-of-treatment visit: 1 week after visit 24
- 8 weeks of follow-up
Afte
Sponsors
Argenx BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 <30×109/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 <30×109/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. Women of childbearing potential: • As defined in Woman of Childbearing Potential, women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before trial medication can be administered • Must be on a stable regimen for at least 1 month of a highly effective or acceptable method of contraception (see Female Contraception) during the trial and for 90 days after the last administration of 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 (see Male Contraception) from signing the ICF through the last administration of the IMP. Male participants are also not allowed to donate sperm during this time.
Exclusion criteria
Exclusion criteria: 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 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 12 months prior to randomization 13. History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia 14. 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 15. 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 (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/mm3 16. Known hypersensitivity reaction to efgartigimod, rHuPH20, or 1 of its excipients 17. Previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP 18. Pregnant or lactating females and those who intend to become pregnant during the trial or within 90 days after last dose of the IMP 19. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening 20. Any other known autoimmune disease that, in the opinion of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint will be analyzed using a Cochran-Mantel-Haenszel statistic test stratified for the stratification factors history of splenectomy (yes versus no), receiving concurrent ITP therapies at baseline (yes versus no), and for baseline platelet count level category (<15×109/L versus =15×109/L) (explanatory note: 9). The treatment effect will be presented as the odds ratio together with its 95% confidence interval (CI) and 2-sided p-value. In addition, an adjusted difference of the proportions with its 95% CI will be provided. NAME OF THE RESULT: Primary endpoint: adult patients with chronic ITP, having an average platelet count of <30×109/L (explanatory note: exponent 9), and, at the start of the trial, either receiving concurrent ITP treatment(s) and having received at least 1 prior therapy for ITP in the past, or not receiving treatment for ITP but having received at least 2 prior treatments for ITP. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: sustained platelet count response defined as achieving platelet counts of =50×109/L (explanatory note: 9) for at least 4 of the 6 visits between week 19 and week 24 of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| The mean changes from baseline in platelet count levels at planned time points and the mean changes from baseline in PRO/QoL at planned time points will be analyzed by means of mixed models for repeated measurements. The model will include fixed effect terms for randomized treatment, baseline platelet level or baseline PRO/QoL, history of splenectomy (yes vs no), and receiving concurrent ITP therapies at baseline (yes vs no). Within-patient correlation will be modeled by assuming an unstructured covariance matrix for the error terms. Least square (LS) means for placebo PH20 SC and efgartigimod PH20 SC will be provided, along with the difference in LS means, 95% two-sided CI, and two-sided p-value. Time to response (defined as the time to achieve 2 consecutive platelet counts of =50×109/L) (note: exponent 9) will be analyzed via Cox proportional hazards regression with fixed effect terms for randomized treatment and baseline platelet level. The model will be stratified by history of splenectomy (yes vs no) and receiving concurrent ITP therapies at baseline (yes vs no), at randomization. The hazard ratio for efgartigimod PH20 SC vs placebo PH20 SC will be provided, along with the associated 95% two-sided CI and two-sided p-value. The data will also be displayed using Kaplan-Meier curves and the median time to response will be displayed by randomized treatment arm. NAME OF THE RESULT: Other secondary endpoints analyses not subject to Alpha Control: The secondary endpoints on overall platelet count response will be analyzed in the same manner as the primary endpoint. The secondary endpoint on extent of disease control will be analyzed in the same manner as the corresponding key secondary endpoint. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The number of cumulative weeks over the planned 24-week treatment peri | — |
Countries
Argentina, Australia, Belize, Bulgaria, Canada, Chile, Colombia, Croatia, Denmark, Ecuador, France, Georgia, Germany, Greece, Ireland, Israel, Italy, Japan, Jordan, Korea South, Latvia, Mexico, New Zealand, Norway, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, South Africa, Spain, Taiwan, Tunisia, Turkey, United Kindgdom, United States
Contacts
Public ContactMARIA CRISTINA EYZAGUIRRE
ICON CLINICAL RESEARCH PERU S.A.
Outcome results
None listed