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

• Sponsor: argenx (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04687072
• Collaborator: (none)
• Enrollment: 219
• Locations: 186
• Arms: 2
• Anticipated Duration (Months): 33.6
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Thrombocytopenia	Biological: Efgartigimod PH20 SC; Other: Placebo PH20 SC	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 11, 2020
• Anticipated Primary Completion Date: Oct 1, 2023
• Anticipated Study Completion Date: Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Efgartigimod PH20 SC Patients receiving efgartigimod PH20 SC treatment	Biological: Efgartigimod PH20 SC; Subcutaneous injection with efgartigimod PH20 SC; Other Names: ARGX-113 PH20 SC
Placebo Comparator: Placebo PH20 SC Patients receiving placebo PH20 SC treatment	Other: Placebo PH20 SC; Subcutaneous injection with placebo PH20 SC

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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]

2. 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)]

3. 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)]

4. 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]

5. 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]

6. 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]

7. Mean change from baseline in platelet count at each visit in the overall population [Up to 35 weeks]

8. 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]

9. 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]

10. 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]

11. Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population [Up to 35 weeks]

12. Severity of the World Health Organization (WHO)-classified bleeding events in the overall population [Up to 35 weeks]

13. Incidence and severity of AEs, AEs of special interest (AESIs), and SAEs in the overall population [Up to 35 weeks]

14. Vital sign measurement: blood pressure in the overall population [Up to 35 weeks]

15. ECG: PR, QT and QRS interval in the overall population [Up to 35 weeks]

16. Laboratory assessments: blood and urine analysis in the overall population [Up to 35 weeks]

17. Rate of receipt of rescue therapy (rescue per patient per month) in the overall population [Up to 35 weeks]

18. 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)]

19. 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]

20. 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]

21. Change from baseline in PRO QoL (Short Form-36 [SF-36]) at planned visits in the overall population [Up to 24 weeks]

22. Incidence of antibodies to efgartigimod and/or rHuPH20 in the overall population [Up to 35 weeks]

23. Prevalence of antibodies to efgartigimod and/or rHuPH20 in the overall population [Up to 35 weeks]

24. Titers of antibodies to efgartigimod and/or rHuPH20 in the overall population [Up to 35 weeks]

25. 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]

26. Serum efgartigimod concentration observed predose (Ctrough) in the overall population [Up to 35 weeks]

27. Pharmacodynamics markers: total IgG and antiplatelet antibody levels in the overall population [Up to 35 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• Male or female, aged ≥18 years at the time the informed consent form (ICF) is signed. Exceptions are made for The Republic of South Korea and Taiwan where, according to local regulatory requirements, legal age is reached at 19 years and 20 years, respectively.

• 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 12 months 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site 0010116	Springdale	Arkansas	United States	72758
2	Investigator Site 0010045	Washington	District of Columbia	United States	20007
3	Investigator Site 0010104	Weston	Florida	United States	33331
4	Investigator Site 0010079	Lisle	Illinois	United States	60187
5	Investigator Site 0010062	Fort Wayne	Indiana	United States	46804
6	Investigator Site 0010083	Detroit	Michigan	United States	48202
7	Investigator Site 0010102	Minneapolis	Minnesota	United States	55455
8	Investigator Site 0010095	Oklahoma City	Oklahoma	United States	73142
9	Investigator Site 0010115	Pittsburgh	Pennsylvania	United States	15222
10	Investigator Site 0540001	Buenos Aires		Argentina
11	Investigator Site 0540004	Buenos Aires		Argentina
12	Investigator Site 0540003	Córdoba		Argentina
13	Investigator Site 0610009	Adelaide		Australia
14	Investigator Site 0610004	Bedford Park		Australia
15	Investigator Site 0610002	Box Hill		Australia
16	Investigator Site 0610010	Clayton		Australia
17	Investigator Site 0610012	Garran		Australia
18	Investigator Site 0610001	Hobart		Australia
19	Investigator Site 0610011	Perth		Australia
20	Investigator Site 0610003	West Perth		Australia
21	Investigator Site 0610005	Westmead		Australia
22	Investigator Site 3590017	Plovdiv		Bulgaria
23	Investigator Site 3590015	Sofia		Bulgaria
24	Investigator Site 0560002	Santiago		Chile
25	Investigator Site 0560004	Temuco		Chile
26	Investigator Site 0560003	Viña Del Mar		Chile
27	Investigator Site 0860003	Beijing		China
28	Investigator Site 0860013	Beijing		China
29	Investigator Site 0860008	Bengbu		China
30	Investigator Site 0860055	Huizhou		China
31	Investigator Site 0860009	Kunming		China
32	Investigator Site 0860012	Nanchang		China
33	Investigator Site 0860014	Shanxi		China
34	Investigator Site 0860015	Shenzhen		China
35	Investigator Site 0860001	Tianjin		China
36	Investigator Site 0860006	Wenzhou		China
37	Investigator Site 0860010	Wuhan		China
38	Investigator Site 0860002	Wuxi		China
39	Investigator Site 0860005	Zhejiang		China
40	Investigator Site 0860011	Zhengzhou		China
41	Investigator Site 0860058	Zhenjiang		China
42	Investigator Site 0450005	Roskilde		Denmark
43	Investigator Site 0330009	Créteil		France
44	Investigator Site 0330018	Montpellier		France
45	Investigator Site 9950006	Tbilisi		Georgia
46	Investigator Site 9950007	Tbilisi		Georgia
47	Investigator Site 9950008	Tbilisi		Georgia
48	Investigator Site 9950009	Tbilisi		Georgia
49	Investigator Site 9950011	Tbilisi		Georgia
50	Investigator Site 9950019	Tbilisi		Georgia
51	Investigator Site 0490012	Gießen		Germany
52	Investigator Site 0300008	Athens		Greece
53	Investigator Site 0300010	Athens		Greece
54	Investigator Site 0300007	Patra		Greece
55	Investigator Site 0300009	Thessaloníki		Greece
56	Investigator Site 3530002	Dublin		Ireland
57	Investigator Site 3530003	Dublin		Ireland
58	Investigator Site 3530001	Galway		Ireland
59	Investigator Site 9720013	Ashkelon		Israel
60	Investigator Site 9720010	Haifa		Israel
61	Investigator Site 9720012	Haifa		Israel
62	Investigator Site 9720008	Jerusalem		Israel
63	Investigator Site 9720011	Jerusalem		Israel
64	Investigator Site 9720007	Petach Tikva		Israel
65	Investigator Site 9720009	Tel Aviv		Israel
66	Investigator Site 0390037	Alessandria		Italy
67	Investigator Site 0390043	Ferrara		Italy
68	Investigator Site 0390045	Meldola		Italy
69	Investigator Site 0390032	Milan		Italy
70	Investigator Site 0390041	Napoli		Italy
71	Investigator Site 0390044	Napoli		Italy
72	Investigator Site 0390015	Novara		Italy
73	Investigator Site 0390035	Potenza		Italy
74	Investigator Site 0390011	Reggio Calabria		Italy
75	Investigator Site 0390046	Rome		Italy
76	Investigator Site 0390033	Terni		Italy
77	Investigator Site 0390036	Varese		Italy
78	Investigator Site 0810056	Chiba		Japan
79	Investigator Site 0810015	Hirakata		Japan
80	Investigator Site 0810010	Hiroshima		Japan
81	Investigator Site 0810053	Kanagawa		Japan
82	Investigator Site 0810051	Kitakyushu		Japan
83	Investigator Site 0810054	Kumamoto		Japan
84	Investigator Site 0810018	Maebashi		Japan
85	Investigator Site 0810057	Morioka		Japan
86	Investigator Site 0810017	Saitama		Japan
87	Investigator Site 0810016	Shibukawa		Japan
88	Investigator Site 0810023	Shimotsuke		Japan
89	Investigator Site 0810039	Shinagawa-Ku		Japan
90	Investigator Site 0810038	Tama		Japan
91	Investigator Site 0810052	Tokyo		Japan
92	Investigator Site 0810048	Tsukuba		Japan
93	Investigator Site 0810044	Yamanashi		Japan
94	Investigator Site 0810012	Ōgaki		Japan
95	Investigator Site 9620002	Amman		Jordan
96	Investigator Site 9620001	Irbid		Jordan
97	Investigator Site 0820005	Seongnam		Korea, Republic of
98	Investigator Site 0820003	Seoul		Korea, Republic of
99	Investigator Site 0820004	Seoul		Korea, Republic of
100	Investigator Site 0820006	Seoul		Korea, Republic of
101	Investigator Site 0820007	Seoul		Korea, Republic of
102	Investigator Site 0820008	Seoul		Korea, Republic of
103	Investigator Site 0520002	Aguascalientes		Mexico
104	Investigator Site 0520004	Chihuahua		Mexico
105	Investigator Site 0520007	Mexico		Mexico
106	Investigator Site 0520003	Monterrey		Mexico
107	Investigator Site 0520001	Oaxaca		Mexico
108	Investigator Site 0640001	Auckland		New Zealand
109	Investigator Site 0640005	Christchurch		New Zealand
110	Investigator Site 0640002	Palmerston North		New Zealand
111	Investigator Site 0470002	Bergen		Norway
112	Investigator Site 0470003	Oslo		Norway
113	Investigator Site 0480014	Lublin		Poland
114	Investigator Site 0480026	Nowy Sącz		Poland
115	Investigator Site 0480037	Skorzewo		Poland
116	Investigator Site 0480039	Toruń		Poland
117	Investigator Site 0480033	Warszawa		Poland
118	Investigator Site 3510006	Braga		Portugal
119	Investigator Site 3510003	Coimbra		Portugal
120	Investigator Site 3510002	Lisboa		Portugal
121	Investigator Site 3510005	Lisboa		Portugal
122	Investigator Site 3510007	Lisboa		Portugal
123	Investigator Site 3510001	Porto		Portugal
124	Investigator Site 3510004	Porto		Portugal
125	Investigator Site 0400005	Bucharest		Romania
126	Investigator Site 0400006	Bucuresti		Romania
127	Investigator Site 0400009	Bucuresti		Romania
128	Investigator Site 0400012	Bucuresti		Romania
129	Investigator Site 0400016	Cluj-Napoca		Romania
130	Investigator Site 0400007	Craiova		Romania
131	Investigator Site 0400011	Sibiu		Romania
132	Investigator Site 0400008	Târgu-Mureş		Romania
133	Investigator Site 0070006	Kaluga		Russian Federation
134	Investigator Site 0070040	Kirov		Russian Federation
135	Investigator Site 0070026	Moscow		Russian Federation
136	Investigator Site 0070038	Nizhny Novgorod		Russian Federation
137	Investigator Site 0070037	Novosibirsk		Russian Federation
138	Investigator Site 0070024	Pyatigorsk		Russian Federation
139	Investigator Site 0070025	Saint Petersburg		Russian Federation
140	Investigator Site 0070039	Smolensk		Russian Federation
141	Investigator Site 0070015	Syktyvkar		Russian Federation
142	Investigator Site 0070012	Tula		Russian Federation
143	Investigator Site 3810006	Belgrade		Serbia
144	Investigator Site 3810008	Kragujevac		Serbia
145	Investigator Site 0270005	George		South Africa
146	Investigator Site 0270003	Johannesburg		South Africa
147	Investigator Site 0270004	Observatory		South Africa
148	Investigator Site 0270001	Pretoria		South Africa
149	Investigator Site 0270002	Randburg		South Africa
150	Investigator Site 0340024	Alava		Spain
151	Investigator Site 0340006	Barcelona		Spain
152	Investigator Site 0340023	Barcelona		Spain
153	Investigator Site 0340037	Madrid		Spain
154	Investigator Site 0340022	Murcia		Spain
155	Investigator Site 0340036	Sabadell		Spain
156	Investigator Site 0340004	Valencia		Spain
157	Investigator Site 8860001	New Taipei City		Taiwan
158	Investigator Site 8860003	Taoyuan		Taiwan
159	Investigator Site 0660001	Bangkok Noi		Thailand
160	Investigator Site 0660002	Bangkok		Thailand
161	Investigator Site 0660003	Bangkok		Thailand
162	Investigator Site 0660005	Bangkok		Thailand
163	Investigator Site 0660008	Bangkok		Thailand
164	Investigator Site 0660004	Chiang Mai		Thailand
165	Investigator Site 0660009	Khon Kaen		Thailand
166	Investigator Site 0660006	Pathum Thani		Thailand
167	Investigator Site 2160006	Sfax		Tunisia
168	Investigator Site 2160001	Sousse		Tunisia
169	Investigator Site 2160002	Tunis		Tunisia
170	Investigator Site 0900007	Adapazarı		Turkey
171	Investigator Site 0900003	Ankara		Turkey
172	Investigator Site 0900006	Ankara		Turkey
173	Investigator Site 0900008	Ankara		Turkey
174	Investigator Site 0900015	Ankara		Turkey
175	Investigator Site 0900016	Edirne		Turkey
176	Investigator Site 0900013	Istanbul		Turkey
177	Investigator Site 0900004	İzmir		Turkey
178	Investigator Site 0900014	Kocaeli		Turkey
179	Investigator Site 0900018	Malatya		Turkey
180	Investigator Site 0900010	Mersin		Turkey
181	Investigator Site 0900009	Samsun		Turkey
182	Investigator Site 0900017	Tekirdağ		Turkey
183	Investigator Site 0900019	Trabzon		Turkey
184	Investigator Site 0440005	Coventry		United Kingdom
185	Investigator Site 0440008	London		United Kingdom
186	Investigator Site 0440014	Truro		United Kingdom

Sponsors and Collaborators

• argenx

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: argenx
• ClinicalTrials.gov Identifier: NCT04687072
• Other Study ID Numbers: ARGX-113-2004
• First Posted: Dec 29, 2020
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic

Study Results

No Results Posted as of Aug 18, 2022