A Study to Assess the Efficacy and Safety of Efgartigimod... | NCT04188379

NCT04188379

ID	Type	Description	Link
2019-002100-41	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
efgartigimod	Experimental	Patient receiving efgartigimod	Biological: efgartigimod
Placebo	Placebo Comparator	Patients receiving placebo	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
efgartigimod	Biological	Intravenous infusion of efgartigimod	efgartigimod

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Chronic 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 Week 19 and 24 of the Trial.	Percentage of participants with chronic ITP with a sustained platelet count response was defined as achieving platelet counts of at least 50 × 10^9/L for at least 4 of the 6 visits between Week 19 and 24 of the study.	From Week 19 up to Week 24

Secondary Outcomes

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 ≥50×10^9/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.	From Week 1 up to Week 24

Eligibility Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Investigator Site 0010038		Tucson	Arizona	85711	United States
Investigator Site 0010045

PubMed Identifier	Type	Citation	Retractions
37778358	Derived	Broome CM, McDonald V, Miyakawa Y, Carpenedo M, Kuter DJ, Al-Samkari H, Bussel JB, Godar M, Ayguasanosa J, De Beuf K, Rodeghiero F, Michel M, Newland A; ADVANCE Investigator Study Group. Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Nov 4;402(10413):1648-1659. doi: 10.1016/S0140-6736(23)01460-5. Epub 2023 Sep 28.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Efgartigimod	Participants receiving efgartigimod efgartigimod: The participants entered a 24-week treatment period and were randomized to receive efgartigimod 10mg/kg IV , weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, subjects were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 15, 2021	Feb 2, 2025

Arm/Group Information

ID	Title	Description
BG000	Efgartigimod	Participants receiving efgartigimod efgartigimod: The participants entered a 24-week treatment period and were randomised to receive efgartigimod 10mg/kg intravenous (IV). The investigational medicinal product (IMP) infusion (efgartigimod) was administered weekly from visits 1 to 4, either weekly or every other week (q2w) from visits 5 to 16, and fixed on the dosing schedule of visit 16 (or the last visit at which IMP was administered) from visits 17 to 24 (ie, either weekly or q2w).
BG001	Placebo	Participants receiving placebo Placebo: The participants entered a 24-week treatment period and were randomized to receive placebo intravenous (IV). The placebo infusion was administered weekly from visits 1 to 4, either weekly or q2w from visits 5 to 16, and fixed on the dosing schedule of visit 16 (or the last visit at which placebo was administered) from visits 17 to 24 (ie, either weekly or q2w).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00046.9± 16.55 BG00151.7± 17.93 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00047 BG00124 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG0004 BG0011 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Chronic 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 Week 19 and 24 of the Trial.

Percentage of participants with chronic ITP with a sustained platelet count response was defined as achieving platelet counts of at least 50 × 10^9/L for at least 4 of the 6 visits between Week 19 and 24 of the study.

Full Analysis Set-Chronic population: all randomized participants with chronic ITP.

Posted

Number

Percentage of participants

From Week 19 up to Week 24

ID	Title	Description
OG000	Efgartigimod	Participants receiving efgartigimod Efgartigimod: The participants entered a 24-week treatment period and were randomized to receive efgartigimod 10mg/kg IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, subjects were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w).
OG001	Placebo	Participants receiving placebo Placebo: The participants entered a 24-week treatment period and were randomized to receive placebo IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w).

Units	Counts
Participants	OG00078 OG00140

Title

Denominators

Categories

Title	Measurements
	OG00021.8 OG0015.0

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		0.0316		Odds Ratio (OR)	4.884			2-Sided	95	1.007	43.591					Superiority

Secondary

Extent of Disease Control Defined as the Number of Cumulative Weeks Over the Planned 24-week Treatment Period With Platelet Counts of ≥50×10^9/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.

Full Analysis Set-Chronic population: all randomized participants with chronic ITP.

Posted

Median

Inter-Quartile Range

Weeks

From Week 1 up to Week 24

ID	Title	Description
OG000	Efgartigimod	Participants receiving efgartigimod Efgartigimod: The participants entered a 24-week treatment period and were randomized to receive efgartigimod 10mg/kg IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w).
OG001	Placebo	Participants receiving placebo Placebo: The participants entered a 24-week treatment period and were randomized to receive placebo IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w)

Secondary

Percentage of Participants With a Sustained Platelet Count Response for at Least 4 of the 6 Visits Between Week 19 and 24 of the Study

Percentage of participants 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.

Full Analysis Set: all randomized participants.

Posted

Number

Percentage of participants

From Week 19 up to Week 24

ID	Title	Description
OG000	Efgartigimod	Participants receiving efgartigimod Efgartigimod: The participants entered a 24-week treatment period and were randomized to receive efgartigimod 10mg/kg IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w).
OG001	Placebo	Participants receiving placebo Placebo: The participants entered a 24-week treatment period and were randomized to receive placebo IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w).

Secondary

Incidence and Severity of the WHO-classified Bleeding Events

Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population.

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 participant population.

Full Analysis Set: all randomized participants.

Posted

Median

Inter-Quartile Range

bleeding events

From Week 1 to Week 24

ID	Title	Description
OG000	Efgartigimod	Participants receiving efgartigimod Efgartigimod: The participants entered a 24-week treatment period and were randomized to receive efgartigimod 10mg/kg IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w)
OG001	Placebo	Participants receiving placebo Placebo: The participants entered a 24-week treatment period and were randomized to receive placebo IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w)

Secondary

Percentage of Participants in the Overall Population Achieving Platelet Counts of at Least 50×10^9/L for at Least 6 of the 8 Visits Between Week 17 and Week 24

Percentage of participants in the overall population achieving platelet counts of at least 50 × 10^9/L for at least 6 of the 8 visits between Week 17 and 24 of the study.

Full Analysis Set: all randomized participants.

Posted

Number

Percentage of participants

From Week 17 up to Week 24

ID	Title	Description
OG000	Efgartigimod	Participants receiving efgartigimod Efgartigimod: The participants entered a 24-week treatment period and were randomized to receive efgartigimod 10mg/kg IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w).
OG001	Placebo	Participants receiving placebo Placebo: The participants entered a 24-week treatment period and were randomized to receive placebo IV, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. From visits 17 to 24, participants were fixed on the dosing schedule at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w)

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chronic myelomonocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0010 events0 affected45 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected86 at risk EG0011 events1 affected45 at risk
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0010 events0 affected45 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected86 at risk EG0011 events1 affected45 at risk
Immune thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected86 at risk EG0011 events1 affected45 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0010 events0 affected45 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected86 at risk EG0010 events0 affected45 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0010 events0 affected45 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected86 at risk EG0011 events1 affected45 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0010 events0 affected45 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected86 at risk EG0011 events1 affected45 at risk
Haematuria	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected86 at risk EG0011 events1 affected45 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0010 events0 affected45 at risk
Appendicitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected86 at risk EG0011 events1 affected45 at risk
COVID-19	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected86 at risk EG0011 events1 affected45 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0010 events0 affected45 at risk
Erysipelas	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0010 events0 affected45 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Haematoma	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG00017 events8 affected86 at risk EG00134 events11 affected45 at risk
Hypertension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0006 events5 affected86 at risk EG0010 events0 affected45 at risk
Asthenia	General disorders	MedDRA 24.1	Systematic Assessment	EG0008 events6 affected86 at risk EG0010 events0 affected45 at risk
Heavy menstrual bleeding	Reproductive system and breast disorders	MedDRA 24.1	Systematic Assessment	EG0009 events5 affected86 at risk EG0014 events3 affected45 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG00024 events8 affected86 at risk EG00112 events8 affected45 at risk
Blood urine present	Investigations	MedDRA 24.1	Systematic Assessment	EG00066 events31 affected86 at risk EG00132 events17 affected45 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG00052 events17 affected86 at risk EG00142 events6 affected45 at risk
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG00020 events14 affected86 at risk EG00122 events6 affected45 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0008 events6 affected86 at risk EG0014 events3 affected45 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0007 events2 affected86 at risk EG0014 events3 affected45 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0004 events3 affected86 at risk EG0016 events4 affected45 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0006 events4 affected86 at risk EG00112 events6 affected45 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00013 events7 affected86 at risk EG00110 events7 affected45 at risk
Oral blood blister	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 events2 affected86 at risk EG0017 events3 affected45 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0009 events5 affected86 at risk EG0012 events2 affected45 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG00010 events5 affected86 at risk EG00113 events6 affected45 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG00021 events13 affected86 at risk EG00120 events12 affected45 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG00012 events7 affected86 at risk EG00112 events4 affected45 at risk
Haematuria	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG00030 events14 affected86 at risk EG00111 events6 affected45 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected86 at risk EG0015 events5 affected45 at risk
COVID-19	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0007 events7 affected86 at risk EG0012 events2 affected45 at risk

ID	Term
D011696	Purpura, Thrombocytopenic
D011693	Purpura
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D057049	Thrombotic Microangiopathies
D013921	Thrombocytopenia
D001791	Blood Platelet Disorders
D000095542	Cytopenia
D006474	Hemorrhagic Disorders
D001327	Autoimmune Diseases
D007154	Immune System Diseases
D006470	Hemorrhage
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D012877	Skin Manifestations
D012816	Signs and Symptoms

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Efgartigimod	Patient receiving efgartigimod efgartigimod: Intravenous infusion of efgartigimod	0	86	7	86	80	86
EG001	Placebo	Patients receiving placebo Placebo: Intravenous infusion of placebo	0	45	7	45	43	45