A Study to Assess the Efficacy and Safety of Efgartigimod in Adult Patients With Primary Immune Thrombocytopenia (ITP).

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 (ITP)

Sponsors

Lead Sponsor: argenx

Source argenx
Brief Summary

This is a randomized, double-blind placebo-controlled multicenter phase 3 trial to evaluate the efficacy and safety of ARGX-113 in patients with primary ITP.

Overall Status Recruiting
Start Date December 16, 2019
Completion Date October 31, 2021
Primary Completion Date June 6, 2021
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Efficacy of efgartigimod compared to placebo in achieving a sustained platelet count response in patients with chronic primary ITP, sustained platelet count response = platelet counts of at least 50×109/L for at least 4/6 visits between week 19 and 24 Up to five weeks (between visits 19 and 24)
Secondary Outcome
Measure Time Frame
Cumulative weeks over the planned 24-week treatment period with platelet counts of at least 50x10^9/L in the chronic ITP population Up to 24 weeks (treatment period)
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 x 10^9/L for at least 4 of the 6 visits between visit 19 and 24 of the trial. Up to five weeks (between visits 19 and 24)
Incidence and severity of the WHO-classified bleeding events Up to 31 weeks, at each visit
Proportion of patients in the overall population achieving platelet counts of at least 50 x 10^9/L for at least 6 of the 8 visits between week 17 and 24 of the trial. Up to 7 weeks (between visits 17 and 24)
Enrollment 156
Condition
Intervention

Intervention Type: Biological

Intervention Name: efgartigimod

Description: Intravenous infusion of efgartigimod

Arm Group Label: efgartigimod

Other Name: ARGX-113

Intervention Type: Other

Intervention Name: Placebo

Description: Intravenous infusion of placebo

Arm Group Label: Placebo

Eligibility

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 American Society of Hematology Criteria, and no known other etiology for thrombocytopenia.

4. Diagnosis supported by a response to a prior ITP therapy (other than thrombopoietin receptor agonists (TPO-RAs)), 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 predose 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 (eg, 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 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 follicle-stimulating hormone (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 postmenopausal 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, being a condom for male patients and a highly effective form of contraception for the female partner of childbearing potential (same as for female patients described in inclusion criterion 8). Male patients practicing true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) can be included.

Sterilized 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 ICF, throughout the duration of the trial, and for 90 days after the last administration of IMP.

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, subcutaneous, 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 crystallized fragment (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 venous 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 randomization. The receipt of any inactivated, sub-unit, polysaccharide, or conjugate vaccine at any time prior to randomization is not considered an exclusion criterion.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Last Name: Antonio Guglietta, MD

Phone: +1 857-350-4834

Email: [email protected]

Location
Facility: Status: Contact:
Investigator Site 4 | Tucson, Arizona, 85711, United States Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 1 | Jacksonville, Florida, 32204, United States Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator site 2 | Ocala, Florida, 34474, United States Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 3 | Quincy, Illinois, 62301, United States Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 5 | Fort Wayne, Indiana, 46804, United States Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 28 | Cleveland, Ohio, 44106, United States Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 80 | Cleveland, Ohio, 44106, United States Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 41 | Linz, Austria Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 40 | Vienna, Austria Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 43 | Brasschaat, Belgium Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 44 | Brugge, Belgium Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 42 | Leuven, Belgium Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 45 | Turnhout, Belgium Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 8 | Yvoir, Belgium Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 47 | Pleven, Bulgaria Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 46 | Sofia, Bulgaria Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 49 | Olomouc, Czechia Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 48 | Ostrava, Czechia Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 50 | Praha, Czechia Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 54 | Clermont-Ferrand, France Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 52 | Créteil, France Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 29 | Le Mans, France Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 53 | Montpellier, France Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 20 | Pessac, France Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 55 | Périgueux, France Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 51 | Rouen, France Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 56 | Düsseldorf, Germany Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 57 | Essen, Germany Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 21 | Budapest, Hungary Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 22 | Debrecen, Hungary Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 58 | Győr, Hungary Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 9 | Nyiregyhaza, Hungary Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 59 | Szombathely, Hungary Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 62 | Campobasso, Italy Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 60 | Monza, Italy Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 61 | Novara, Italy Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 34 | Ravenna, Italy Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 23 | Reggio Calabria, Italy Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 35 | Rimini, Italy Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 33 | Siena, Italy Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 63 | Trieste, Italy Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 65 | Bunkyō-Ku, Japan Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 30 | Hirakata, Japan Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 24 | Hiroshima, Japan Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator site 12 | Iruma, Japan Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator site 11 | Isehara, Japan Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 31 | Kashiwa, Japan Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 16 | Maebashi, Japan Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator site 15 | Minato-Ku, Japan Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 66 | Niigata, Japan Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 10 | Sapporo, Japan Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator site 13 | Shibukawa, Japan Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 32 | Shimotsuke, Japan Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 64 | Shinjuku-Ku, Japan Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 6 | Den Haag, Netherlands Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 67 | Rotterdam, Netherlands Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 7 | Rotterdam, Netherlands Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]om
Investigator Site 69 | Brzozów, Poland Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 70 | Bydgoszcz, Poland Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 25 | Chorzów, Poland Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 68 | Gdańsk, Poland Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 18 | Kaluga, Russian Federation Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 75 | Moscow, Russian Federation Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 73 | Petrozavodsk, Russian Federation Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 72 | Rostov-on-Don, Russian Federation Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 74 | Saint Petersburg, Russian Federation Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 71 | Tula, Russian Federation Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 17 | Ufa, Russian Federation Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 27 | Barcelona, Spain Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 36 | Barcelona, Spain Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 26 | Madrid, Spain Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 37 | Madrid, Spain Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 39 | Madrid, Spain Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 14 | Palma De Mallorca, Spain Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 38 | Sevilla, Spain Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 76 | Valencia, Spain Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 77 | Valencia, Spain Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator Site 78 | Luts'k, Ukraine Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Investigator site 19 | Mykolayiv, Ukraine Recruiting Antonio Guglietta, MD 857-350-4834 [email protected]
Investigator Site 79 | London, United Kingdom Recruiting Antonio Guglietta, MD 857-350-4834 +1 [email protected]
Location Countries

Austria

Belgium

Bulgaria

Czechia

France

Germany

Hungary

Italy

Japan

Netherlands

Poland

Russian Federation

Spain

Ukraine

United Kingdom

United States

Verification Date

August 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: efgartigimod

Type: Experimental

Description: Patient receiving efgartigimod

Label: Placebo

Type: Placebo Comparator

Description: Patients receiving placebo

Acronym ADVANCE
Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov