A study to assess the efficacy and safety of efgartigimod in adult patients with primary immune thrombocytopenia (an autoimmune disorder that destructs platelets, blood cells that help with clotting, and can lead to easy or excessive bruising and bleeding)

• Register: EUCTR
• Last refreshed on: 31 August 2020
• Main ID: EUCTR2019-002100-41-GB
• Date of registration: 05/08/2020
• Prospective Registration: No
• Primary sponsor: argenx BVBA
• Public title: A study to assess the efficacy and safety of efgartigimod in adult patients with primary immune thrombocytopenia (an autoimmune disorder that destructs platelets, blood cells that help with clotting, and can lead to easy or excessive bruising and bleeding)
• Scientific 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 - ADVANCE
• Date of first enrolment: 10/01/2020
• Target sample size: 156
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-002100-41
• 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

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

Contacts

• Name: Regulatory
• Affiliation: argenx BVBA

• Name: Regulatory
• Affiliation: argenx BVBA

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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).
2. Male or female patient aged =18 years.
3. Confirmed ITP diagnosis, at least 3 months before randomization and according to the ASH Criteria, and no known other 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 (and no single platelet count of >35×10^9/L) from 3 qualifying counts, 2 during the screening period and the pre-dose platelet count at visit 1. The 3 platelet counts must be over the course of 7 to 14 days, with at least 2 days between any 2 counts.
6. 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.
Permitted concurrent ITP medications include oral corticosteroids, oral immunosuppressants, dapsone/danazol, fostamatinib and/or oral TPO-RAs.
Patients not receiving concurrent ITP therapy are also eligible for the trial if they have not received prior ITP therapy for at least 4 weeks prior to baseline, and 6 months in case of prior ITP therapy with an anti-CD20 therapy (e.g, rituximab).
7. Women of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline before study medication (infusion) can be administered. Women are considered of childbearing potential unless they are post-menopausal (defined by continuous amenorrhea) for at least 1 year with an FSH of >40 IU/L or are surgically sterilized (ie, women who had a hysterectomy, both ovaries surgically removed, or have a documented permanent female sterilization procedure including tubal ligation). Follicle-stimulating hormone can be used to confirm post-menopausal status in amenorrheic patients not on hormonal replacement therapy.
8. Women of childbearing potential should use a highly effective method of contraception (ie, pregnancy rate of less than 1% per year) during the trial and for 90 days after the last administration of the IMP. They must be on a stable regimen, for at least 1 month:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
-oral
-intravaginal
- transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation:
- oral
- injectable
- implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system
• bilateral tubal occlusion
• vasectomized partner (provided that the partner is the sole sexual partner of the trial participant and documented aspermia post procedure)
• continuous abstinence from heterosexual sexual contact. Sexual abstinence is only allowable if it is the preferred and usual lifestyle of the patient. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not acceptable.
9. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use effective double contraception, bei
Exclusion criteria:
1. ITP/thrombocytopenia associated with another condition, eg, lymphoma, chronic lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune thrombocytopenia, or thrombocytopenia associated with myeloid dysplasia.
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), 4 weeks prior to randomization.
5. Use of anti-CD20 therapy (eg, rituximab) within 6 months prior to randomization.
6. Use of romiplostim within 4 weeks prior to randomization.
7. Undergone splenectomy less than 4 weeks prior to randomization.
8. Use of any other investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) prior to randomization.
9. Use of monoclonal antibodies or Fc fusion proteins, other than those previously indicated, within 3 months prior to randomization.
10. At the screening visit, clinically significant laboratory abnormalities as below:
- Hemoglobin =9 g/dL.
OR
- International normalized ratio >1.5 or activated partial thromboplastin time >1.5×ULN.
OR
- Total IgG level <6 g/L.
11. 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.
12. Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments.
13. History of any major thrombotic or embolic event (eg, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis) within 12 months prior to randomization.
14. History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia.
15. 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.
16. Patients with known serum-positivity or who test positive for an active viral infection at screening with: Hepatitis B Virus (HBV) (except patients who are anti HBs Ab positive because of HBV vaccination), Hepatitis C Virus, HIV.
17. 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 patient at undue risk.
18. Patients with known medical history of hypersensitivity to any of the ingredients of the IMP.
19. Patients who previously participated in a clinical trial with efgartigimod.
20. Pregnant or lactating females.
21. Employees of the investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial center, as well as family of the employees or the investigator.
22. Patients who received a live-attenuated vaccine within 4 weeks before randomisation. The receipt of any inactivated, sub-unit, polysaccharide, or conjugate vaccine at any time prior to randomisation is not considered an exclusio

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

Health Condition(s) or Problem(s) studied

Primary immune thrombocytopenia
MedDRA version: 23.0 Level: LLT Classification code 10050245 Term: Autoimmune thrombocytopenia System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Efgartigimod
Product Code: ARGX-113
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Efgartigimod
CAS Number: 1821402-21-4
Current Sponsor code: ARGX-113
Other descriptive name: ARGX-113
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of efgartigimod compared to placebo in achieving a sustained platelet count response in patients with primary chronic immune thrombocytopenia (ITP), with a sustained platelet count response defined as 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.

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

Primary end point(s): Proportion of patients 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.

Timepoint(s) of evaluation of this end point: Between week 19 and 24 of the trial.

Secondary Outcome(s)

Secondary end point(s): Key Secondary Efficacy Endpoints Subject to Alpha Control:
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.
2. 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 50×10^9/L for at least 4 of the 6 visits between week 19 and 24 of the trial.
3. Incidence and severity of the WHO-classified bleeding events in the overall population.
4. Proportion of patients 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 trial.

Timepoint(s) of evaluation of this end point: 1. Over the 24-week treatment
2. Between week 19 and 24
3. At each visit
4. Between week 17 and 24

Secondary ID(s)

2019-002100-41-NL

ARGX-113-1801

Source(s) of Monetary Support

argenx BVBA

Ethics review

Status: Approved
Approval date: 10/01/2020
Contact: