A Phase 3 study to evaluate the efficacy and safety of efgartigimod PH 20 Subcutaneous in adult patients with primary immune thrombocytopenia.

• Register: EUCTR
• Last refreshed on: 8 January 2024
• Main ID: EUCTR2020-004032-21-BG
• Date of registration: 15/03/2021
• Prospective Registration: Yes
• Primary sponsor: argenx BV
• Public title: A Phase 3 study to evaluate the efficacy and safety of efgartigimod PH 20 Subcutaneous in adult patients with primary immune thrombocytopenia.
• Scientific 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 - ADVANCE SC
• Date of first enrolment: 17/05/2021
• Target sample size: 219
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004032-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Bulgaria, Chile, China, Colombia, Denmark, France, Georgia, Germany, Greece, Ireland, Israel, Italy, Japan, Jordan, Korea, Republic of, Mexico, New Zealand, Norway, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, South Africa, Spain, Taiwan, Thailand, Tunisia, Turkey, United Kingdom, United States

Contacts

• Name: Regulatory
• Affiliation: argenx BV

• Name: Regulatory
• Affiliation: argenx BV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ability to understand the requirements of the trial and provide written informed consent (including consent for the use and disclosure of research-related health information), willing and able to comply with the trial protocol procedures (including attending the required trial visits)
2. 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.
3. 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
4. Diagnosis supported by a response to a prior ITP therapy (other than TPO-RAs), in the opinion of the investigator
5. Mean platelet count of <30×10^9/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.
6. A documented history of a platelet count of <30×10^9/L before screening
7. 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.
Note: Participants not receiving concurrent ITP therapy are also eligible for the trial if they have not received prior ITP therapy for at least 4 weeks before baseline, and 6 months in case of prior ITP therapy with an anti-CD20 therapy (eg, rituximab).
8a. Agree to use contraceptive measures consistent with local regulations and the following:
• Male participants: refer to the protocol, Section 10.6.2.2.
• Female participants of childbearing potential (defined in the protocol, Section 10.6.1.1) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving IMP. Contraceptive requirements are provided in the protocol, Section 10.6.2.1.
9. [Removed in Global Protocol Amendment 3 (v4.0)]
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 191
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion criteria:
1. 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
2. Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) within 4 weeks prior to randomization
3. Use of any transfusions within 4 weeks prior to randomization
4. Use of Ig (IV, SC, or intramuscular route) or plasmapheresis (PLEX) within 4 weeks prior to randomization
5. Use of romiplostim within 4 weeks prior to randomization
6. Undergone splenectomy less than 4 weeks prior to randomization
7. Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP
8. 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)
9. 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
10. 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:
a. Adequately treated basal cell or squamous cell skin cancer
b. Carcinoma in situ of the cervix
c. Carcinoma in situ of the breast or
d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
11. Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments
12. History of any major thrombotic or embolic event (eg, myocardial infarction, stroke, deep venous thrombosis, or pulmonary embolism) within 12 months prior to randomization
13. History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia
14. 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).
15. 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.
16. 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
17. Positive serum test at screening for an active viral infection with any of the following conditions:
a. Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless associated with a negative HBV DNA test
(https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf)
b. Hepatitis C virus (HCV) based on HCV-antibody assay (unless associated with a negative HCV RNA test)
c. 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
18

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Primary immune thrombocytopenia (ITP)
MedDRA version: 23.0 Level: LLT Classification code 10083843 Term: Primary immune thrombocytopenia System Organ Class: 100000004851

Intervention(s)

Product Name: efgartigimod PH20 SC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: efgartigimod alfa
CAS Number: 1821402-21-4
Current Sponsor code: ARGX-113
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 180-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet counts of =50×10^9/L for at least 4 of the 6 visits between week 19 and week 24 of the trial

Main Objective: To evaluate the efficacy of efgartigimod PH20 SC compared to placebo PH20 SC in achieving a sustained platelet count response in patients with chronic primary ITP, with a sustained platelet count response defined as platelet counts of =50×10^9/L for at least 4 of the 6 visits between week 19 and week 24 of the trial

Timepoint(s) of evaluation of this end point: Up to 5 weeks (between week 19 –24)

Secondary Objective: • To evaluate the efficacy of efgartigimod PH20 SC compared to placebo PH20 SC in overall platelet count response
• To evaluate the incidence and severity of bleeding events while receiving treatment with efgartigimod PH20 SC compared to placebo PH20 SC
•To evaluate the safety and tolerability of efgartigimod PH20 SC administered qw or every other week (q2w) compared to placebo PH20 SC
• To evaluate the use of rescue treatment and changes in concurrent ITP therapy while receiving treatment with efgartigimod PH20 SC compared to placebo PH20 SC
• To evaluate the effects of efgartigimod PH20 SC treatment on quality-of-life (QoL) measures and patient-reported outcomes (PRO) compared to placebo PH20 SC
• To assess the immunogenicity of efgartigimod and rHuPH20
• To assess the pharmacokinetics (PK) of efgartigimod PH20 SC
• To assess the pharmacodynamic (PD) effects of efgartigimod PH20 SC

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Up to 24 weeks
2. Up to 5 weeks (between week 19-24)
3. Up to 7 weeks (between week 17-24)
4. Up to 24 weeks
5. Up to 12 weeks
6. Up to 12 weeks
7. Up to 35 weeks
8. Up to 35 weeks
9. Up to 24 weeks
10. Up to 24 weeks
11. Up to 35 weeks
12.Up to 35 weeks
13. Up to 35 weeks
14. Up to 35 weeks
15. Up to 23 weeks (between week 12-35)
16. Up to 24 weeks
17. Up to 35 weeks
18. Up to 35 weeks
19. Up to 35 weeks
20. Up to 35 weeks
21. Up to 35 weeks

Secondary end point(s): 1. 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 (Key Secondary Endpoint 1)
2. Proportion of patients in the overall population (chronic and persistent ITP) with a sustained platelet count response defined as achieving platelet counts of =50×10^9/L for at least 4 of the 6 visits between week 19 and week 24 (Key Secondary Endpoint 2)
3. Proportion of patients in the overall population achieving platelet counts of =50×10^9/L for at least 6 of the 8 visits between week 17 and 24 of the trial (Key Secondary Endpoint 3)
4. Proportion of patients in the overall population with overall platelet response defined as achieving a platelet count of =50×10^9/L on at least 4 occasions at any time during the 24-week treatment period
5. Extent of disease control defined as the number of cumulative weeks until week 12 with platelet counts of =50×10^9/L in the overall population
6. Proportion of patients in the overall population with overall platelet response defined as achieving a platelet count of =50×10^9/L on at least 4 occasions at any time until week 12
7. Mean change from baseline in platelet count at each visit in the overall population
8. Time to response defined as the time to achieve 2 consecutive platelet counts of =50×10^9/L in the overall population
9. The number of cumulative weeks over the planned 24-week treatment period with platelet counts of =30×10^9/L and =20×10^9/L above baseline in the overall population
10. In patients with baseline platelet count of <15×10^9/L, the number of cumulative weeks over the planned 24-week treatment period with platelet counts of =30×10^9/L and =20×10^9/L above baseline in the overall population
11. Incidence and severity of the World Health Organization (WHO)-classified bleeding events in the overall population (Key Secondary Endpoint 4)
12. Incidence and severity of AEs, AEs of special interest (AESIs), and SAEs in the overall population
13. Vital signs, ECG, and laboratory assessments in the overall population
14. Rate of receipt of rescue therapy (rescue per patient per month) in the overall population
15. Proportion of patients for whom dose and/or frequency of concurrent ITP therapies have increased at week 12 or later in the overall population
16. Change from baseline in PRO (Functional Assessment of Chronic Illness Therapy Fatigue Scale [FACIT-Fatigue], Functional Assessment of Cancer Therapy questionnaire-Th6 [Fact-Th6]) and QoL (Short Form-36 [SF-36]) at planned visits in the overall population
17. Incidence and prevalence of antibodies to efgartigimod and/or rHuPH20 in the overall population
18. Titers of antibodies to efgartigimod and/or rHuPH20 in the overall population
19. Presence of neutralizing antibodies (NAb) against efgartigimod and/or rHuPH20, and titers of NAb against efgartigimod and/or rHuPH20 in the overall population
20. Serum efgartigimod concentration observed predose (Ctrough) in the overall population
21. Pharmacodynamics markers: total IgG and antiplatelet antibody levels in the overall population

Secondary ID(s)

ARGX-113-2004

2020-004032-21-IE

Source(s) of Monetary Support

argenx BV

Ethics review

Status: Approved
Approval date: 17/05/2021
Contact: