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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 16 December 2019
Main ID:  EUCTR2019-002100-41-NL
Date of registration: 07/08/2019
Prospective Registration: Yes
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
Date of first enrolment: 01/11/2019
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 Canada Czech Republic France Germany Hungary
Italy Japan Netherlands Poland Russian Federation Spain Switzerland Ukraine
United Kingdom United States
Contacts
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7 B-9052 Zwijnaarde Belgium
Telephone: +32 9 310 3400
Email: regulatory@argenx.com
Affiliation:  argenx BVBA
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7 B-9052 Zwijnaarde Belgium
Telephone: +32 9 310 3400
Email: regulatory@argenx.com
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 (for Japan only, patients aged =20 years).
3. Confirmed ITP diagnosis, at least 3 months before randomization and according to the ASH Criteria 2011, 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. Patients have previously received at least 1 typical ITP therapy. Patients receiving permitted concurrent ITP treatments 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, and/or eltrombopag.
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 prior to infusion. Women of childbearing potential are defined as all female patients unless they are post-menopausal (defined by continuous amenorrhea) for at least 1 year with an FSH of >40 IU/L or are surgically sterile (i.e. women who had a hysterectomy, both ovaries surgically removed, or have documented tubal ligation or any other documented permanent female sterilization procedure). Follicle-stimulating hormone can be used to confirm post-menopausal status in amenorrheic patients not on hormonal replacement therapy if the value is within the post-menopausal range per the laboratory.
8. Women of childbearing potential should use a highly effective method of contraception (i.e. 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, of combined estrogen and progestogen hormonal contraception with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or agree upon 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, of which 1 method must be a barrier method and the other another barrier method or highly effective form of cont

Exclusion criteria:
1. ITP/thrombocytopenia associated with another condition, e.g. lymphoma, chronic lymphocytic leukemia, viral infection, autoimmune disorders, thyroid disease, human immunodeficiency virus (HIV), hepatitis, induced or alloimmune thrombocytopenia, or thrombocytopenia associated with myeloid dysplasia.
2. Use of anticoagulants (e.g. 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 IVIg, SC or intramuscular route, or plasmapheresis (PLEX), 4 weeks prior to randomization.
5. Use of anti-CD20 therapy (e.g. rituximab) within 6 months prior to randomization.
6. Use of romiplostim within 4 weeks prior to randomization.
7. Use of fostamatinib within 4 weeks prior to randomization.
8. Undergone splenectomy less than 4 weeks prior to randomization.
9. Use of any other investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) prior to randomization.
10. Use of monoclonal antibodies or Fc fusion proteins, other than those previously indicated, within 3 months prior to randomization.
11. 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.
12. 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.
13. Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments.
14. History of any thrombotic or embolic event within 12 months prior to randomization.
15. History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia.
16. History of a recent or planned major surgery (that involves major organs e.g. brain, heart, lung, liver, bladder, or gastrointestinal tract) within 4 weeks of randomization.
17. 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.
18. Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than ITP (e.g. cardiovascular, pulmonary, hematologic, gastrointestinal, endocrine, hepatic, renal, neurological, malignancy, infectious diseases, uncontrolled diabetes) despite appropriate treatments which could put the patient at undue risk.
19. Patients with known medical history of hypersensitivity to any of the ingredients of the IMP.
20. Patients who previously participated in a clinical trial with efgartigimod.
21. Pregnant or lactating


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Primary immune thrombocytopenia
MedDRA version: 20.1 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 alfa
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)

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 biweekly.
- 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.
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 visits 19 and 24 of the trial.
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 visits 19 and 24 of the trial.
Timepoint(s) of evaluation of this end point: Between visits 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 visits 19 and 24 of the trial.
3. Incidence and severity of the WHO-classified bleeding events.
Other Secondary Endpoints Not Subject to Alpha Control:
4. Percentage of patients 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 visit 12, with platelet counts of =50×10^9/L.
6. Percentage of patients with overall platelet response defined as achieving a platelet count of =50×10^9/L on at least 4 occasions at any time until visit 12.
7. Mean change from baseline in platelet count at each visit.
8. Time to response defined as the time to achieve 2 consecutive platelet counts of =50×10^9/L.
9. Rate of receipt of rescue therapy (rescue per patient per month).
10. Proportion of patients for whom dose and/or frequency of concurrent ITP therapies have increased at visit 12 or later.
11. The number of cumulative weeks over the planned 24-week treatment period with platelet counts =30×10^9/L and at least 20×10^9/L above baseline.
12. 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 at least 20×10^9/L above baseline.
13. Change from baseline in PRO (FACIT-Fatigue, Fact-Th6) and QoL (SF-36) at planned visits.
14. Incidence of anti-drug antibodies (ADA) to efgartigimod.
15. Pharmacokinetic parameters of efgartigimod.
16. Pharmacodynamics markers: Total IgG, IgG isotypes (IgG1, IgG2, IgG3, IgG4), antiplatelet antibody levels.
Safety Evaluation
17. Evaluate the incidence and severity of AEs, AE(S)Is, and SAEs.
18. Evaluate vital signs, ECG, and laboratory assessments

Timepoint(s) of evaluation of this end point: 1. Over the planned 24-week treatment
2. Between visits 19 and 24 of the trial
3. At each visit
4. at any time during the 24-week treatment period
5. Until visit 12
6. At any time until visit 12
7. At each visit
8. At each visit
9. At each visit
10. At visit 12 or later
11. Over the planned 24-week treatment period
12. Over the planned 24-week treatment period
13. At planned visits
14. Screening, Baseline, week 4, 8, 13, 19, 23 of the IV treatment Period , End-of-Treatment, Follow-up 2, Unscheduled Visit
15. IV treatment period, End-of-Treatment, Follow-up 1, Follow-up 2, Unscheduled Visit
16. IV treatment period, End-of-Treatment, Follow-up 1, Follow-up 2, Unscheduled Visit
17. At each visit
18. Please refer to schedule of assessment in the protocol
Secondary ID(s)
ARGX-113-1801
Source(s) of Monetary Support
argenx BVBA
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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