A Study to Evaluate the Efficacy and Safety of Efgartigimod PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia

Primary Immune Thrombocytopenia Clinical Trial

— ADVANCE SC  

Official title:

A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and the Safety of Efgartigimod (ARGX-113) PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04687072
• Other study ID #: ARGX-113-2004
• Status: Completed
• Phase: Phase 3
• Start date: December 11, 2020
• Est. completion date: October 9, 2023

Study information

• Verified date: November 2023
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group trial to evaluate the efficacy, safety, and effect on QoL/PRO of efgartigimod PH20 SC treatment in adult patients with primary ITP.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 207
• Est. completion date: October 9, 2023
• Est. primary completion date: October 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Ability to understand the requirements of the trial and provide written informed consent, willing and able to comply with the trial protocol procedures

• Is at least the local age of consent for clinical studies when signing the ICF.

• 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

• Diagnosis supported by a response to a prior ITP therapy (other than TPO-RAs), in the opinion of the investigator

• Mean platelet count of <30×10E9/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.

• A documented history of a platelet count of <30×10E9/L before screening

• 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.

-Agree to use contraceptive measures consistent with local regulations and the protocol

Exclusion criteria:

• 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

• Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) within 4 weeks prior to randomization

• Use of any transfusions within 4 weeks prior to randomization

• Use of Ig (IV, SC, or intramuscular route) or plasmapheresis (PLEX) within 4 weeks prior to randomization

• Use of romiplostim within 4 weeks prior to randomization

• Undergone splenectomy less than 4 weeks prior to randomization

• Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP

• 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)

• 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: Adequately treated basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast or Incidental histological finding of prostate cancer (TNM stage T1a or T1b)

• 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 (eg, myocardial infarction, stroke, deep venous thrombosis, or pulmonary embolism) within 5 years prior to randomization

• History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia

• Evidence of an active clinically significant bleeding of an organ or internal mucosal bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic procedure based on the investigator's judgment (eg, intracranial hemorrhage, pulmonary hemorrhage, bleeding with ongoing need for packed red blood cell transfusion)

• Estimated high risk of a clinically significant bleeding of an organ or internal mucosal bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic procedure according to the investigator's judgment

• 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

• Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless associated with a negative HBV DNA test, Hepatitis C virus (HCV) based on HCV-antibody assay (unless associated with a negative HCV RNA test), 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

• Known hypersensitivity reaction to efgartigimod, rHuPH20, or 1 of its excipients

• Previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP

• Pregnant or lactating or intends to become pregnant during the trial

• Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening

• Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of ITP or put the participant at undue risk

• Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than ITP (eg, cardiovascular, pulmonary, hematologic, gastrointestinal, endocrine, hepatic, renal, neurological, malignancy, infectious diseases, uncontrolled diabetes) despite appropriate treatments which could put the participant at undue risk

• Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse

• Received a live/live-attenuated vaccine less than 4 weeks before screening. The receipt of any inactivated, sub-unit, polysaccharide, or conjugate vaccine at any time before screening is not considered an exclusion criterion

Related Conditions & MeSH terms

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

Intervention

Biological:
• Efgartigimod PH20 SC
Subcutaneous injection with efgartigimod PH20 SC

Other:
• Placebo PH20 SC
Subcutaneous injection with placebo PH20 SC

Locations

Country	Name	City	State
Argentina	Investigator Site 0540001	Buenos Aires
Argentina	Investigator Site 0540004	Buenos Aires
Argentina	Investigator Site 0540003	Córdoba
Australia	Investigator Site 0610009	Adelaide
Australia	Investigator Site 0610004	Bedford Park
Australia	Investigator Site 0610002	Box Hill
Australia	Investigator Site 0610010	Clayton
Australia	Investigator Site 0610012	Garran
Australia	Investigator Site 0610001	Hobart
Australia	Investigator Site 0610011	Perth
Australia	Investigator Site 0610003	West Perth
Australia	Investigator Site 0610005	Westmead
Bulgaria	Investigator Site 3590017	Plovdiv
Bulgaria	Investigator Site 3590015	Sofia
Chile	Investigator Site 0560002	Santiago
Chile	Investigator Site 0560004	Temuco
Chile	Investigator Site 0560003	Viña Del Mar
China	Investigator Site 0860003	Beijing
China	Investigator Site 0860013	Beijing
China	Investigator Site 0860008	Bengbu
China	Investigator Site 0860055	Huizhou
China	Investigator Site 0860009	Kunming
China	Investigator Site 0860012	Nanchang
China	Investigator Site 0860014	Shanxi
China	Investigator Site 0860015	Shenzhen
China	Investigator Site 0860001	Tianjin
China	Investigator Site 0860006	Wenzhou
China	Investigator Site 0860010	Wuhan
China	Investigator Site 0860002	Wuxi
China	Investigator Site 0860005	Zhejiang
China	Investigator Site 0860011	Zhengzhou
China	Investigator Site 0860058	Zhenjiang
China	Investigator site 0860062	Zhenjiang
Denmark	Investigator Site 0450005	Roskilde
France	Investigator Site 0330009	Créteil
France	Investigator Site 0330018	Montpellier
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 9950019	Tbilisi
Germany	Investigator site 0490008	Essen
Germany	Investigator Site 0490012	Gießen
Greece	Investigator Site 0300008	Athens
Greece	Investigator Site 0300010	Athens
Greece	Investigator Site 0300007	Patra
Greece	Investigator Site 0300009	Thessaloníki
Ireland	Investigator Site 3530002	Dublin
Ireland	Investigator Site 3530003	Dublin
Ireland	Investigator Site 3530001	Galway
Israel	Investigator Site 9720013	Ashkelon
Israel	Investigator Site 9720010	Haifa
Israel	Investigator Site 9720012	Haifa
Israel	Investigator Site 9720008	Jerusalem
Israel	Investigator Site 9720011	Jerusalem
Israel	Investigator Site 9720007	Petach Tikva
Israel	Investigator Site 9720009	Tel Aviv
Italy	Investigator Site 0390037	Alessandria
Italy	Investigator Site 0390043	Ferrara
Italy	Investigator Site 0390045	Meldola
Italy	Investigator site 0390014	Milan
Italy	Investigator Site 0390032	Milan
Italy	Investigator Site 0390041	Napoli
Italy	Investigator Site 0390044	Napoli
Italy	Investigator Site 0390015	Novara
Italy	Investigator Site 0390035	Potenza
Italy	Investigator Site 0390011	Reggio Calabria
Italy	Investigator site 0390018	Reggio Emilia
Italy	Investigator Site 0390046	Rome
Italy	Investigator Site 0390033	Terni
Italy	Investigator Site 0390036	Varese
Japan	Investigator Site 0810056	Chiba
Japan	Investigator Site 0810015	Hirakata
Japan	Investigator Site 0810010	Hiroshima
Japan	Investigator Site 0810053	Kanagawa
Japan	Investigator Site 0810051	Kitakyushu
Japan	Investigator Site 0810054	Kumamoto
Japan	Investigator Site 0810018	Maebashi
Japan	Investigator Site 0810057	Morioka
Japan	Investigator Site 0810012	Ogaki
Japan	Investigator Site 0810017	Saitama
Japan	Investigator Site 0810016	Shibukawa
Japan	Investigator Site 0810023	Shimotsuke
Japan	Investigator Site 0810039	Shinagawa-Ku
Japan	Investigator Site 0810038	Tama
Japan	Investigator Site 0810052	Tokyo
Japan	Investigator Site 0810048	Tsukuba
Japan	Investigator Site 0810044	Yamanashi
Jordan	Investigator Site 9620002	Amman
Jordan	Investigator Site 9620001	Irbid
Korea, Republic of	Investigator Site 0820005	Seongnam
Korea, Republic of	Investigator Site 0820003	Seoul
Korea, Republic of	Investigator Site 0820004	Seoul
Korea, Republic of	Investigator Site 0820006	Seoul
Korea, Republic of	Investigator Site 0820007	Seoul
Korea, Republic of	Investigator Site 0820008	Seoul
Mexico	Investigator Site 0520002	Aguascalientes
Mexico	Investigator Site 0520004	Chihuahua
Mexico	Investigator Site 0520007	Mexico
Mexico	Investigator Site 0520003	Monterrey
Mexico	Investigator Site 0520001	Oaxaca
New Zealand	Investigator Site 0640001	Auckland
New Zealand	Investigator Site 0640005	Christchurch
New Zealand	Investigator Site 0640002	Palmerston North
Norway	Investigator Site 0470002	Bergen
Norway	Investigator Site 0470003	Oslo
Poland	Investigator Site 0480013	Katowice
Poland	Investigator Site 0480014	Lublin
Poland	Investigator Site 0480026	Nowy Sacz
Poland	Investigator Site 0480037	Skorzewo
Poland	Investigator Site 0480039	Torun
Poland	Investigator Site 0480033	Warszawa
Portugal	Investigator Site 3510006	Braga
Portugal	Investigator Site 3510003	Coimbra
Portugal	Investigator Site 3510002	Lisboa
Portugal	Investigator Site 3510005	Lisboa
Portugal	Investigator Site 3510007	Lisboa
Portugal	Investigator Site 3510001	Porto
Portugal	Investigator Site 3510004	Porto
Romania	Investigator Site 0400005	Bucharest
Romania	Investigator Site 0400006	Bucuresti
Romania	Investigator Site 0400009	Bucuresti
Romania	Investigator Site 0400012	Bucuresti
Romania	Investigator Site 0400016	Cluj-Napoca
Romania	Investigator Site 0400007	Craiova
Romania	Investigator Site 0400011	Sibiu
Romania	Investigator Site 0400008	Târgu-Mures
Russian Federation	Investigator Site 0070006	Kaluga
Russian Federation	Investigator Site 0070040	Kirov
Russian Federation	Investigator Site 0070026	Moscow
Russian Federation	Investigator Site 0070038	Nizhny Novgorod
Russian Federation	Investigator Site 0070037	Novosibirsk
Russian Federation	Investigator Site 0070024	Pyatigorsk
Russian Federation	Investigator Site 0070025	Saint Petersburg
Russian Federation	Investigator Site 0070039	Smolensk
Russian Federation	Investigator Site 0070015	Syktyvkar
Russian Federation	Investigator Site 0070012	Tula
Serbia	Investigator Site 3810006	Belgrade
Serbia	Investigator Site 3810008	Kragujevac
South Africa	Investigator Site 0270005	George
South Africa	Investigator Site 0270003	Johannesburg
South Africa	Investigator Site 0270004	Observatory
South Africa	Investigator Site 0270001	Pretoria
South Africa	Investigator Site 0270002	Randburg
Spain	Investigator Site 0340024	Alava
Spain	Investigator Site 0340006	Barcelona
Spain	Investigator Site 0340007	Barcelona
Spain	Investigator Site 0340023	Barcelona
Spain	Investigator Site 0340037	Madrid
Spain	Investigator Site 0340022	Murcia
Spain	Investigator Site 0340036	Sabadell
Spain	Investigator site 0340013	Sevilla
Spain	Investigator Site 0340004	Valencia
Taiwan	Investigator Site 8860001	New Taipei City
Taiwan	Investigator Site 8860003	Taoyuan
Thailand	Investigator Site 0660002	Bangkok
Thailand	Investigator Site 0660003	Bangkok
Thailand	Investigator Site 0660005	Bangkok
Thailand	Investigator Site 0660008	Bangkok
Thailand	Investigator Site 0660001	Bangkok Noi
Thailand	Investigator Site 0660004	Chiang Mai
Thailand	Investigator Site 0660009	Khon Kaen
Thailand	Investigator Site 0660006	Pathum Thani
Tunisia	Investigator Site 2160006	Sfax
Tunisia	Investigator Site 2160001	Sousse
Tunisia	Investigator Site 2160002	Tunis
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 0900010	Mersin
Turkey	Investigator Site 0900009	Samsun
Turkey	Investigator Site 0900017	Tekirdag
Turkey	Investigator Site 0900019	Trabzon
United Kingdom	Investigator site 0440011	Bradford
United Kingdom	Investigator Site 0440005	Coventry
United Kingdom	Investigator Site 0440008	London
United Kingdom	Investigator Site 0440041	London
United Kingdom	Investigator Site 0440014	Truro
United States	Investigator site 0010112	Chicago	Illinois
United States	Investigator site 0010193	Chicago	Illinois
United States	Investigator site 0010040	Columbus	Ohio
United States	Investigator Site 0010083	Detroit	Michigan
United States	Investigator Site 0010062	Fort Wayne	Indiana
United States	Investigator site 0010042	Iowa City	Iowa
United States	Investigator Site 0010079	Lisle	Illinois
United States	Investigator site 0010036	Los Angeles	California
United States	Investigator Site 0010102	Minneapolis	Minnesota
United States	Investigator Site 0010095	Oklahoma City	Oklahoma
United States	Investigator Site 0010115	Pittsburgh	Pennsylvania
United States	Investigator Site 0010116	Springdale	Arkansas
United States	Investigator Site 0010045	Washington	District of Columbia
United States	Investigator Site 0010104	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Chile,  China,  Denmark,  France,  Georgia,  Germany,  Greece,  Ireland,  Israel,  Italy,  Japan,  Jordan,  Korea, Republic of,  Mexico,  New Zealand,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Taiwan,  Thailand,  Tunisia,  Turkey,  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 =50×10E9/L for at least 4 of the 6 visits between week 19 and week 24 of the trial		Up to 5 weeks (between week 19 -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		Up to 24 weeks
Secondary	Proportion of patients in the overall population (chronic and persistent ITP) with a sustained platelet count response defined as achieving platelet counts of =50×10E9/L for at least 4 of the 6 visits between week 19 and week 24		Up to 5 weeks (between week 19-24)
Secondary	Proportion of patients in the overall population achieving platelet counts of =50×10E9/L for at least 6 of the 8 visits between week 17 and 24 of the trial		Up to 7 weeks (between week 17-24)
Secondary	Proportion of patients in the overall population with overall platelet response defined as achieving a platelet count of =50×10E9/L on at least 4 occasions at any time during the 24-week treatment period		Up to 24 weeks
Secondary	Extent of disease control defined as the number of cumulative weeks until week 12 with platelet counts of =50×10E9/L in the overall population		Up to 12 weeks
Secondary	Proportion of patients in the overall population with overall platelet response defined as achieving a platelet count of =50×10E9/L on at least 4 occasions at any time until week 12		Up to 12 weeks
Secondary	Mean change from baseline in platelet count at each visit in the overall population		Up to 35 weeks
Secondary	Time to response defined as the time to achieve 2 consecutive platelet counts of =50×10E9/L in the overall population		Up to 35 weeks
Secondary	The number of cumulative weeks over the planned 24-week treatment period with platelet counts of =30×10E9/L and =20×10E9/L above baseline in the overall population		Up to 24 weeks
Secondary	In patients with baseline platelet count of <15×10E9/L, the number of cumulative weeks over the planned 24-week treatment period with platelet counts of =30×10E9/L and =20×10E9/L above baseline in the overall population		Up to 24 weeks
Secondary	Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population		Up to 35 weeks
Secondary	Severity of the World Health Organization (WHO)-classified bleeding events in the overall population		Up to 35 weeks
Secondary	Proportion of patients with an International Working Group (IWG) response		Up to 35 weeks
Secondary	Proportion of patients with an International Working Group (IWG) complete response		Up to 35 weeks
Secondary	Proportion of patients with an International Working Group (IWG) initial response		Up to 35 weeks
Secondary	Incidence and severity of AEs, AEs of special interest (AESIs), and SAEs in the overall population		Up to 35 weeks
Secondary	Vital sign measurement: blood pressure in the overall population		Up to 35 weeks
Secondary	ECG: PR, QT and QRS interval in the overall population		Up to 35 weeks
Secondary	Laboratory assessments: blood and urine analysis in the overall population		Up to 35 weeks
Secondary	Rate of receipt of rescue therapy (rescue per patient per month) in the overall population		Up to 35 weeks
Secondary	Proportion of patients for whom dose and/or frequency of concurrent ITP therapies have increased at week 12 or later in the overall population		Up to 23 weeks (between week 12-35)
Secondary	Change from baseline in PRO (Functional Assessment of Chronic Illness Therapy Fatigue Scale [FACIT-Fatigue] at planned visits in the overall population		Up to 24 weeks
Secondary	Change from baseline in PRO Functional Assessment of Cancer Therapy questionnaire-Th6 [Fact-Th6]) at planned visits in the overall population		Up to 24 weeks
Secondary	Change from baseline in PRO QoL (Short Form-36 [SF-36]) at planned visits in the overall population		Up to 24 weeks
Secondary	Incidence of antibodies to efgartigimod and/or rHuPH20 in the overall population		Up to 35 weeks
Secondary	Prevalence of antibodies to efgartigimod and/or rHuPH20 in the overall population		Up to 35 weeks
Secondary	Titers of antibodies to efgartigimod and/or rHuPH20 in the overall population		Up to 35 weeks
Secondary	Presence of neutralizing antibodies (NAb) against efgartigimod and/or rHuPH20, and titers of NAb against efgartigimod and/or rHuPH20 in the overall population		Up to 35 weeks
Secondary	Serum efgartigimod concentration observed predose (Ctrough) in the overall population		Up to 35 weeks
Secondary	Pharmacodynamics markers: total IgG and antiplatelet antibody levels in the overall population		Up to 35 weeks