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

• ClinicalTrials.gov Identifier: NCT04188379
• Recruitment Status: Completed
• First Posted: December 5, 2019
• Last Update Posted: March 7, 2024
• Sponsor: argenx
• Information provided by (Responsible Party): argenx

Tracking Information

• First Submitted Date: December 4, 2019
• First Posted Date: December 5, 2019
• Last Update Posted Date: March 7, 2024
• Actual Study Start Date: December 16, 2019
• Actual Primary Completion Date: February 3, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 2, 2023)

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. [ Time Frame: Up to five weeks (between visits 19 and 24) ]

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.

• Original Primary Outcome Measures (submitted: December 4, 2019): Proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet counts of at least 50 x 10^9/L for at least 4 of the 6 visits between visits 19 and 24 of the trial. [ Time Frame: Up to five weeks (between visits 19 and 24) ]

Current Secondary Outcome Measures (submitted: February 2, 2023)

• 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 [ Time Frame: Up to 24 weeks (treatment period) ]
  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.
• 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 [ Time Frame: Up to five weeks (between visits 19 and 24) ]
  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.
• Incidence and severity of the WHO-classified bleeding events [ Time Frame: Up to 24 weeks (From Week 1 to Week 24) ]
  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.
• 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. [ Time Frame: Up to 7 weeks (between visits 17 and 24) ]
  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.

Original Secondary Outcome Measures (submitted: December 4, 2019)

• Number of cumulative weeks over the planned 24-week treatment period with platelet counts of at least 50x10^9/L in the chronic ITP population [ Time Frame: 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 x 10^9/L for at least 4 of the 6 visits between visit 19 and 24 of the trial. [ Time Frame: Up to five weeks (between visits 19 and 24) ]
• Incidence and severity of the WHO-classified bleeding events [ Time Frame: Up to 31 weeks, at each visit ]
• 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 visits 17 and 24 of the trial. [ Time Frame: Up to 7 weeks (between visits 17 and 24) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Efficacy and Safety of Efgartigimod in Adult Patients With Primary Immune Thrombocytopenia (ITP).
• Official Title: 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
• Brief Summary: This is a randomized, double-blind placebo-controlled multicenter phase 3 trial to evaluate the efficacy and safety of ARGX-113 in participants with primary ITP.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Primary Immune Thrombocytopenia

Intervention

• Biological: efgartigimod
  Intravenous infusion of efgartigimod
  Other Name: ARGX-113
• Other: Placebo
  Intravenous infusion of placebo

Study Arms

• Experimental: efgartigimod
  Patient receiving efgartigimod
  Intervention: Biological: efgartigimod
• Placebo Comparator: Placebo
  Patients receiving placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 10, 2021): 131
• Original Estimated Enrollment (submitted: December 4, 2019): 156
• Actual Study Completion Date: February 3, 2022
• Actual Primary Completion Date: February 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.
• 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.
• 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 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.

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 certain medications before the start of the studies (more details in the protocol)
• 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 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), Hepatitis C virus (HCV), Human immunodeficiency virus (HIV)
• Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than ITPdespite 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. More details in the protocol

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Bulgaria, Czechia, France, Georgia, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04188379
• Other Study ID Numbers: ARGX-113-1801; 2019-002100-41 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: argenx
• Original Responsible Party: Same as current
• Current Study Sponsor: argenx
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: argenx
• Verification Date: March 2024