A long-term study to assess the safety and efficacy 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: 10 June 2024
• Main ID: EUCTR2019-002101-21-PL
• Date of registration: 15/07/2021
• Prospective Registration: No
• Primary sponsor: argenx BV
• Public title: A long-term study to assess the safety and efficacy 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, Open-label, Long-term Trial to Evaluate the Safety and Efficacy of Efgartigimod (ARGX-113) 10 mg/kg Intravenous in Adult Patients With Primary Immune Thrombocytopenia - ADVANCE+
• Date of first enrolment: 09/12/2020
• Target sample size: 156
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-002101-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• 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, Czechia, France, Georgia, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Turkey, Ukraine, 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, 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. Patients enrolled in the ARGX-113-1801 trial who completed the 24-week trial period.
3. Women of childbearing potential must have a negative urine pregnancy test at baseline before trial 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 a FSH of >40 IU/L or are surgically sterilized (ie, women who had a hysterectomy, a bilateral salpingectomy, 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.
4. 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. 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 that aspermia was documented 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.
• male or female condom with or without spermicide
• cap, diaphragm, or sponge with spermicide.
5. In addition to the above criteria, for patients who want to continue receiving efgartigimod during an additional 52-week treatment period (only applicable in case efgartigimod is not yet commercially available for patients with primary ITP, or becomes available through another
patient program for patients with primary ITP):
6. Ability to understand the requirements of the additional 52-week treatment period 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).
7. Patient has completed a 52-week treatment period.
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 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion criteria:
1. Introduction or continuation of non-permitted medications during the ARGX-113-1801 trial (such as anti-CD20 therapy, romiplostim, monoclonal antibodies, Fc fusion proteins or live/live-attenuated vaccines).
2. Pregnant or lactating women, and those intending to become pregnant during the trial or within 90 days after the last dosing.
3. Patients with known medical history of hypersensitivity to any of the ingredients of efgartigimod.
4. Use of any other investigational drug or participation in any other investigational trial.


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

Health Condition(s) or Problem(s) studied

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

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

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
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: To evaluate the long-term safety of efgartigimod in adult patients with primary immune thrombocytopenia (ITP).

Primary end point(s): Frequency and severity of AEs, vital signs, and laboratory assessments.

Secondary Objective: First 52-week treatment period only:
• To evaluate the long-term efficacy of efgartigimod on overall platelet count response.
• To explore the potential for reduction in concurrent ITP therapy.
• To evaluate the effects of efgartigimod treatment on quality-of-life (QoL) measures and patient-reported outcomes (PRO).
• To evaluate the incidence and severity of bleeding events while receiving treatment with efgartigimod.
• To evaluate the use of rescue treatment while receiving treatment with efgartigimod.
• To assess the pharmacodynamic (PD) effects of efgartigimod.
• To evaluate the pharmacokinetics (PK) of efgartigimod.
First 52-week treatment period and additional 52-week treatment periods:
• To assess the immunogenicity of efgartigimod.

Timepoint(s) of evaluation of this end point: Frequency and severity of AEs - at each visit
Vital signs - at baseline visit (week 1), followed by every even week (week 2 to week 52) and Early discontinuation, follow-up 1 and 2, unscheduled visits.
Laboratory assessments - please refer to protocol Table 1 Schedule of Assessments for various laboratory assessments

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Over the 52-week treatment period
2. Over the 52-week treatment period
3. At each visit
4. At each visit
5. Over the 52-week treatment period
6. Over the 52-week treatment period
7. Between week 19 and 24
8. Between week 17 and 24
9. At each visit
10. At each visit
11. At each visit
12. PRO: Visits 1, 5, 9, 13, 17, 21, 25, 33, 41, 49, 52 of Treatment period, Early Discontinuation
QoL: Weeks 1, 9, 17, 25, 33, 41, 49, 52 of Treatment period, Early Discontinuation
13. and 14. Weeks 1, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Treatment period, Early Discontinuation, Follow-up 1/2, Unscheduled Visit
First 52-week treatment period and additional 52-week treatment periods:
15. At planned visits per schedule of assessments in the protocol

Secondary end point(s): First 52-week treatment period only:
1. Extent of disease control defined as the percentage of weeks in the trial with platelet counts of =50×10^9/L.
2. Percentage of patients with overall platelet count response defined as achieving a platelet count of =50×10^9/L on at least 4 occasions at any time during the 52-week treatment period.
3. Mean change from baseline in platelet count at each visit.
4. For patients rolling-over from the ARGX-113-1801 trial with a platelet count of <30×10^9/L: time to response is defined as the time to achieve 2 consecutive platelet counts of =50×10^9/L.
5. The percentage of weeks in the trial with platelet counts of =30×10^9/L and at least 20×10^9/L above baseline.
6. In patients with baseline platelet count of <15×10^9/L in the current trial (ARGX-113-1803), the percentage of weeks in the trial with platelet counts of =30×10^9/L and at least 20×10^9/L above baseline.
7. In patients with first exposure to efgartigimod: proportion of patients who achieve a sustained platelet 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.
8. In patients with first exposure to efgartigimod: 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.
9. Rate of receipt of rescue therapy (rescue per patient per month).
10. Reduction in concurrent ITP therapy.
11. Incidence and severity of the WHO-classified bleeding events.
12. Change from baseline in PRO (FACIT-Fatigue, Fact-Th6) and QoL (SF-36) at planned visits.
13.Pharmacokinetic parameter of efgartigimod: serum concentration observed predose (Ctrough).
14. Pharmacodynamics markers: total IgG
First 52-week treatment period and additional 52-week treatment periods:
15. Incidence of anti-drug antibodies (ADA) to efgartigimod.

Secondary ID(s)

2019-002101-21-NL

ARGX-113-1803

Source(s) of Monetary Support

argenx BV

Ethics review

Status: Approved
Approval date: 26/11/2020
Contact: