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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Immune Thrombocytopenia
• Intervention / Treatment: Biological: efgartigimod; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria
    • Investigator Site 0430004
  • Vienna, Austria
    • Investigator Site 0430002
  • Vienna, Austria
    • Investigator Site 0430003
• Belgium
  • Brasschaat, Belgium
    • Investigator Site 0320012
  • Brugge, Belgium
    • Investigator Site 0320011
  • Leuven, Belgium
    • Investigator Site 0320015
  • Turnhout, Belgium
    • Investigator Site 0320014
  • Verviers, Belgium
    • Investigator Site 0320020
  • Yvoir, Belgium
    • Investigator site 0320002
• Bulgaria
  • Pleven, Bulgaria
    • Investigator Site 3590001
  • Sofia, Bulgaria
    • Investigator Site 3590002
• Czechia
  • Brno, Czechia
    • Investigator Site 4200001
  • Olomouc, Czechia
    • Investigator Site 4200008
  • Ostrava, Czechia
    • Investigator Site 4200006
  • Praha, Czechia
    • Investigator Site 4200007
• France
  • Clermont-Ferrand, France
    • Investigator Site 0330019
  • Créteil, France
    • Investigator Site 0330009
  • Le Mans, France
    • Investigator Site 0330015
  • Montpellier, France
    • Investigator Site 0330018
  • Pessac, France
    • Investigator Site 0330008
  • Périgueux, France
    • Investigator Site 0330016
  • Rouen, France
    • Investigator Site 0330017
• Georgia
  • Tbilisi, Georgia
    • Investigator Site 9950006
  • Tbilisi, Georgia
    • Investigator Site 9950007
  • Tbilisi, Georgia
    • Investigator Site 9950008
  • Tbilisi, Georgia
    • Investigator Site 9950009
  • Tbilisi, Georgia
    • Investigator Site 9950011
  • Tbilisi, Georgia
    • Investigator Site 9950012
• Germany
  • Düsseldorf, Germany
    • Investigator Site 0490010
  • Essen, Germany
    • Investigator Site 0490008
  • Gießen, Germany
    • Investigator Site 0490012
• Hungary
  • Budapest, Hungary
    • Investigator Site 0360004
  • Debrecen, Hungary
    • Investigator Site 0360006
  • Győr, Hungary
    • Investigator Site 0360015
  • Nyiregyhaza, Hungary
    • Investigator site 0360010
  • Szombathely, Hungary
    • Investigator Site 0360014
• Italy
  • Campobasso, Italy
    • Investigator Site 0390012
  • Milan, Italy
    • Investigator Site 0390014
  • Monza, Italy
    • Investigator Site 0390020
  • Novara, Italy
    • Investigator Site 0390015
  • Ravenna, Italy
    • Investigator Site 0390010
  • Reggio Calabria, Italy
    • Investigator Site 0390011
  • Reggio Emilia, Italy
    • Investigator Site 0390018
  • Rimini, Italy
    • Investigator Site 0390019
  • Roma, Italy
    • Investigator Site 0390021
  • Siena, Italy
    • Investigator Site 0390009
  • Torino, Italy
    • Investigator Site 0390017
  • Trieste, Italy
    • Investigator Site 0390016
• Japan
  • Bunkyō-Ku, Japan
    • Investigator Site 0810024
  • Hirakata, Japan
    • Investigator Site 0810015
  • Hiroshima, Japan
    • Investigator Site 0810010
  • Iruma, Japan
    • Investigator site 0810017
  • Isehara, Japan
    • Investigator site 0810011
  • Kashiwa, Japan
    • Investigator Site 0810022
  • Maebashi, Japan
    • Investigator site 0810018
  • Minato-Ku, Japan
    • Investigator site 0810020
  • Niigata, Japan
    • Investigator Site 0810021
  • Sapporo, Japan
    • Investigator site 0810014
  • Shibukawa, Japan
    • Investigator site 0810016
  • Shimotsuke, Japan
    • Investigator Site 0810023
  • Shinjuku-Ku, Japan
    • Investigator Site 0810025
• Netherlands
  • Den Haag, Netherlands
    • Investigator site 0310006
  • Rotterdam, Netherlands
    • Investigator Site 0310005
  • Rotterdam, Netherlands
    • Investigator Site 0310007
• Poland
  • Białystok, Poland
    • Investigator Site 0480030
  • Brzozów, Poland
    • Investigator Site 0480015
  • Bydgoszcz, Poland
    • Investigator Site 0480010
  • Chorzów, Poland
    • Investigator Site 0480013
  • Gdańsk, Poland
    • Investigator Site 0480012
  • Katowice, Poland
    • Investigator Site 0480008
  • Lodz, Poland
    • Investigator Site 0480011
  • Lublin, Poland
    • Investigator Site 0480014
  • Nowy Sącz, Poland
    • Investigator site 0480026
  • Wrocław, Poland
    • Investigator Site 0480016
• Russian Federation
  • Kaluga, Russian Federation
    • Investigator site 0070006
  • Petrozavodsk, Russian Federation
    • Investigator Site 0070007
  • Rostov-on-Don, Russian Federation
    • Investigator Site 0070013
  • Syktyvkar, Russian Federation
    • Investigator Site 0070015
  • Tula, Russian Federation
    • Investigator Site 0070012
  • Ufa, Russian Federation
    • Investigator site 0070010
• Spain
  • Barcelona, Spain
    • Investigator Site 0340006
  • Barcelona, Spain
    • Investigator Site 0340007
  • Burgos, Spain
    • Investigator Site 0340030
  • Madrid, Spain
    • Investigator Site 0340009
  • Madrid, Spain
    • Investigator Site 0340014
  • Madrid, Spain
    • Investigator Site 0340015
  • Palma De Mallorca, Spain
    • Investigator site 0340012
  • Sevilla, Spain
    • Investigator Site 0340013
  • Valencia, Spain
    • Investigator Site 0340004
  • Valencia, Spain
    • Investigator Site 0340011
• Turkey
  • Adana, Turkey
    • Investigator Site 0900002
  • Adapazarı, Turkey
    • Investigator Site 0900007
  • Ankara, Turkey
    • Investigator Site 0900003
  • Ankara, Turkey
    • Investigator Site 0900006
  • Ankara, Turkey
    • Investigator Site 0900008
  • Ankara, Turkey
    • Investigator Site 0900015
  • Edirne, Turkey
    • Investigator Site 0900016
  • Istanbul, Turkey
    • Investigator Site 0900013
  • Izmir, Turkey
    • Investigator Site 0900004
  • Kocaeli, Turkey
    • Investigator Site 0900014
  • Malatya, Turkey
    • Investigator Site 0900018
  • Manisa, Turkey
    • Investigator Site 0900005
  • Mersin, Turkey
    • Investigator Site 0900010
  • Samsun, Turkey
    • Investigator Site 0900009
  • Tekirdağ, Turkey
    • Investigator Site 0900017
  • Trabzon, Turkey
    • Investigator Site 0900019
• Ukraine
  • Kharkiv, Ukraine
    • Investigator Site 3800022
  • Mykolayiv, Ukraine
    • Investigator site 3800006
• United Kingdom
  • London, United Kingdom
    • Investigator Site 0440008
  • Rhyl, United Kingdom
    • Investigator Site 0440010
  • Southampton, United Kingdom
    • Investigator Site 0440012
  • Truro, United Kingdom
    • Investigator Site 0440014
• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Investigator Site 0010038
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Investigator Site 0010045
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Investigator Site 0010034
    • Ocala, Florida, United States, 34474
      • Investigator site 0010037
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Investigator Site 0010042
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Investigator Site 0010046
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Investigator Site 0010049
    • Columbus, Ohio, United States, 44106
      • Investigator Site 0010040
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Investigator Site 0010041

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: efgartigimod; Patient receiving efgartigimod	Biological: efgartigimod; Intravenous infusion of efgartigimod; Other Names: ARGX-113
Placebo Comparator: Placebo; Patients receiving placebo	Other: Placebo; Intravenous infusion of placebo

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: argenx

Publications and helpful links

Helpful Links

• Website for patients

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2019
• Primary Completion (Actual): February 3, 2022
• Study Completion (Actual): February 3, 2022

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: immune thrombocytopenia; bleeding events; sustained platelet count response
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Cytopenia; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: ARGX-113-1801; 2019-002100-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No