| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Primary Immune Thrombocytopenia |
|
| E.1.1.1 | Medical condition in easily understood language |
| Primary Immune Thrombocytopenia |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10074678 |
| E.1.2 | Term | Primary immune thrombocytopenic purpura |
| E.1.2 | System Organ Class | 100000004851 |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the safety of efgartigimod (ARGX-113)in adult patients with primary immune thrombocytopenia (ITP) |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the effectiveness of efgartigimod (ARGX-113)in adult patients with primary immune thrombocytopenia (ITP) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Ability to understand the requirements of the trial, to provide written informed consent (or patient’s legally authorised representative) (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 patients aged ≥18 years.
3. Confirmed ITP diagnosis, at least 3 months before Baseline and according to the American Society of Haematology Criteria 2011, and no known other etiology for thrombocytopenia.
4. Diagnosis supported by a response to a prior ITP therapy, in the opinion of the investigator.
5. Mean platelet count of <30×10⁹/L (and no single platelet count of >35×10⁹/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 receiving permitted concurrent ITP treatments at Baseline, must have been stable in dose and frequency for at least 4 weeks prior to Baseline. Permitted concurrent ITP medications include oral corticosteroids, oral immunosuppressants, 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.
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 a follicle-stimulating hormone (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 sterilisation 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, vasectomised 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-sterilised 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 contraception as described above for women of childbearing potential (e.g. condom with spermicidal cream or jelly, 1 hormonal plus 1 barrier method, IUD plus 1 barrier method, or 2 simultaneous barrier methods). Male patients practicing true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) can be included. Sterilised male patients who have had vasectomy with documented aspermia post procedure can be included. In addition, male patients are not allowed to donate sperm during this period from signing of Informed Consent Form, throughout the duration of the trial, and for 90 days after the last administration of IMP.
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|
| E.4 | Principal exclusion criteria |
1. ITP 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. Symptoms of, or receiving treatment for, systemic lupus erythematosus, antiphospholipid antibody syndrome or any other clinically documented autoimmune disease other than ITP.
3. Use of anticoagulants, or any drug with antiplatelet effect (e.g. acetylsalicylic acid [aspirin] or other salicylate containing medications, cyclooxygenase inhibitors, adenosine diphosphate receptor inhibitors, phosphodiesterase inhibitors, glycoprotein IIB/IIIA inhibitors, adenosine reuptake inhibitors, thromboxane inhibitors, antimalarials, and prostacyclin) within 4 weeks prior to Baseline.
4. Use of any blood support or transfusion within 4 weeks prior to Baseline.
5. Use of IVIg, SC or intramuscular route, or PLEX, 4 weeks prior to Baseline.
6. Use of rituximab within 6 months prior to Baseline.
7. Use of romiplostim within 4 weeks prior to Baseline.
8. Use of fostamatinib within 4 weeks prior to Baseline.
9. Undergone splenectomy less than 4 weeks prior to Baseline.
10. Use of any other biological therapy or investigational drug than those previously indicated within 3 months or 5 half-lives of the drug (whichever is longer) prior to Baseline.
11. History of vaccination within the last 4 weeks prior to Baseline, or with a planned vaccination during the trial, except for seasonal vaccination (e.g. influenza vaccine).
12. At the screening visit, clinically significant laboratory abnormalities as below: • Hemoglobin ≤9 g/dL.
• International normalized ratio >1.5 or activated partial thromboplastin time >1.5×ULN.
• Total IgG level <6 g/L.
- OR -
13. 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.
14. History of cerebrovascular accident or myocardial infarction within the last 12 months before Baseline. Current severe/unstable angina, arrhythmia, or at risk of ventricular arrhythmia, symptomatic congestive heart failure (New York Heart Association Class III or IV).
15. Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments.
16. History of any thrombotic or embolic event within 12 months prior to the baseline visit.
17. History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia.
18. History of a recent major surgery (that involves major organs e.g. brain, heart, lung, liver, bladder, or gastrointestinal tract) within 4 weeks of Baseline.
19. 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 seropositive because of HBV vaccination), Hepatitis C Virus, HIV.
20. 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.
21. Patients with known medical history of hypersensitivity to any of the ingredients of the IMP.
22. Patients who previously participated in a clinical trial with efgartigimod.
23. Pregnant or lactating females.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The Primary Endpoints of the study are:
• Evaluate the incidence, severity, and seriousness of AEs
• Evaluate vital signs and laboratory assessments |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Various time points throughout the study |
|
| E.5.2 | Secondary end point(s) |
All secondary endpoints assessing activity of efgartigimod will focus on
measures of response derived from platelet counts. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Various time points throughout the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Hungary |
| Spain |
| Ukraine |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LVLS - End-of-Trial is defined as last patient last visit |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 20 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 20 |
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