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

Primary Immune Thrombocytopenia Clinical Trial

— ADVANCE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04188379
• Other study ID #: ARGX-113-1801
• Secondary ID: 2019-002100-41
• Status: Completed
• Phase: Phase 3
• Start date: December 16, 2019
• Est. completion date: February 3, 2022

Study information

• Verified date: March 2024
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: February 3, 2022
• Est. primary completion date: February 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Primary Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Biological:
• efgartigimod
Intravenous infusion of efgartigimod

Other:
• Placebo
Intravenous infusion of placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Czechia,  France,  Georgia,  Germany,  Hungary,  Italy,  Japan,  Netherlands,  Poland,  Russian Federation,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)