|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Primary immune thrombocytopenia
|Medical condition in easily understood language
|Low levels of the blood cells that prevent bleeding (platelets)
|Diseases [C] - Blood and lymphatic diseases [C15]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The primary objective is to evaluate the safety and tolerability of TAK-079 in patients with persistent/chronic primary ITP.
|Secondary objectives of the trial
|The secondary objective is to assess the effects of TAK-079 administration on platelet counts in patients with persistent/chronic primary ITP.
|Trial contains a sub-study
|Principal inclusion criteria
|Each patient must meet all the following inclusion criteria to be to be randomized to treatment:
1. Age 18 years or older and able and willing to comply with study procedures.
2. Diagnosed with ITP that has persisted for ≥3 months, diagnosed in accordance to The American Society of Hematology 2011 Evidence-based Practice Guideline for Immune Thrombocytopenia or the International Consensus Report on The Investigation and Management of Primary Immune Thrombocytopenia as locally applicable.
3. Has a mean platelet count of <30,000/µL (and individually =
35,000/µL) on at least 2 measurements at least 1 week apart during
4.Diagnosis of ITP supported by a prior response to an ITP therapy
(other than a TPO-RA)
that achieved a platelet count of =50,000/µL.
5. If receiving standard background treatment for ITP, treatment should be stable in dose and frequency for at least 4 weeks before dosing.
a) Permitted standard background treatments may include: 1 oral corticosteroid; ±1 immunosuppressant from the following list: azathioprine, danazol, dapsone, cyclosporine, mycophenolate mofetil, mycophenolate sodium; ±1 TPO-RA (romiplostim, eltrombopag, avatrombopag); ±fostamatinib. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy as opposed to pulse therapy. High-dose pulse steroid therapy is not
allowed within 14 days before Day 1.
b) The dose of any permitted standard background therapy must be expected to remain stable through the study, unless dose reduction is required because of toxicities.
6. Female patients of childbearing potential are required to have a negative pregnancy test. Both female patients of childbearing potential and male patients must practice an effective, reliable,
and approved contraceptive regimen during the study and for up to 90 days or 5 half-lives, whichever is longer, after discontinuation of treatment.
7. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
|Principal exclusion criteria
|Patients meeting any of the following exclusion criteria are not to be randomized to treatment:
1. Use of anticoagulants or any drug with antiplatelet effect (such as aspirin) within 3 weeks before screening.
2. History of any thrombotic or embolic event within 12 months before screening.
3. History of splenectomy within 3 months before screening.
4. Use of IVIg, subcutaneous immunoglobulin or anti-D treatment within 4 weeks of screening, or an expectation that any therapy besides the patient's standard background therapies may be used for treatment of thrombocytopenia (eg, a rescue therapy) between
screening and dosing.
5. Diagnosed with chronic obstructive pulmonary disease (COPD) or asthma, and a prebronchodilatory forced expiratory volume in 1 second (FEV1) <50% of predicted normal.
Note: FEV1 testing is required for patients suspected of having COPD or asthma.
6. Use of rituximab or any mAb for immunomodulation within 4 months before first dosing.
Note: Patients with prior exposure to rituximab must have CD19 counts within the normal range at screening.
7. Use of immunosuppressants (such as cyclophosphamide, vincristine) other than permitted oral immunosuppressants within 6 months before first dosing.
8. Diagnosed with myelodysplastic syndrome.
9. Has received a live vaccine within 4 weeks before screening or has any live vaccine planned during the study.
10. Currently experiencing any medical condition that, in the opinion of the investigator, might interfere with the patient’s participation in the study (such as significant cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinologic, hepatic, renal, neurologic, malignancy, or infectious disease), that poses an added risk for the patient, or could confound the assessment of the patient.
11. Pregnancy or lactation during screening period or on Day 1 before first dose of study drug.
12. Participation in any other investigational drug study or exposure to other investigational agent within 4 weeks or 5 half-lives, whichever is longer, before Day 1.
13. Has had an opportunistic infection ≤12 weeks before initial study dosing or is currently undergoing treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks
of study dosing is allowed, as long as the lesion has resolved without systemic therapy
before Day 1.
14. Exhibits clinically significant laboratory abnormalities at screening:
a) Alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal (ULN).
b) Total bilirubin >1.5 × ULN (Note: Patients with a confirmed diagnosis of Gilbert syndrome that is documented in the patient’s medical record are not excluded based on this criterion).
c) Absolute neutrophil count <1500/mm3.
d) Hemoglobin <8 g/dL.
e) IgG <500 mg/dL.
f) Lymphocyte count <500/mm3.
g) Creatinine clearance, CrCl, <30 mL/min (ie, CrCl ≥30 mL/min is allowed).
15. Has a positive T-cell interferon-γ release assay (TIGRA) (results through QuantiFERON TB Gold test or T-Spot/Elispot) at the screening visit, noting the following:
a) A purified protein derivative (PPD) skin test may be used as a replacement, if TIGRA testing is not available.
b) Patients with an indeterminate TIGRA result must meet the following criteria:
– Has a negative PPD skin test (defined as <5 mm induration).
– Is at low risk of acquiring TB (eg, avoids close contact with TB positive individual[s]), and/or chest x-ray ≤6 months before the screening visit that is consistent with no evidence of latent or active TB).
16. Has a serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
17. Has a positive test result for hepatitis B surface antigen or hepatitis
B core antibody, or hepatitis C antibody, or HIV antibody/antigen, at screening.However, an individual who has a known history of chronic hepatitis C and has been treated and fully cured of the disease, confirmed with a negative hepatitis C virus RNA polymerase chain reaction test at screening, is not excluded on the basis of positive hepatitis C antibody alone.
18. Has a history of severe allergic or anaphylactic reactions to recombinant proteins or excipients used in the TAK-079/placebo formulation.
|E.5 End points
|Primary end point(s)
|The primary endpoint is the percentage of patients with TEAEs including Grade 3 or higher events, SAEs, and AEs leading to TAK-079 discontinuation.
|Timepoint(s) of evaluation of this end point
|TEAEs that occur after administration of the first dose of TAK-079 and through to the end of the SFP period will be tabulated and followed until resolution.
|Secondary end point(s)
|The secondary efficacy endpoint assesses the effects of TAK-079 administration on changes in the platelet count, through the following 4 endpoints:
1. Percentage of patients with a platelet response. Platelet response is defined as a platelet count ≥50,000/μL and ≥20,000/μL above baseline on at least 2 visits without a dosing period–permitted rescue treatment in the previous 4 weeks and without any other previous rescue therapy.
2. The percentage of patients with a complete platelet response. Complete platelet response is defined as a platelet count ≥100,000/μL on at least 2 visits without a dosing period–permitted rescue treatment in the previous 4 weeks and without any other previousrescue therapy.
3. The percentage of patients with a clinically meaningful platelet response. A clinically meaningful platelet response is defined as a platelet count ≥20,000/μL above baseline on at least 2 visits without a dosing period–permitted rescue treatment in the previous 4 weeks and without any other previousrescue therapy.
4. The percentage of patients with a hemostatic platelet response. A hemostatic platelet response is defined for patients with a baseline platelet count of <15,000/μL who achieve a platelet count of ≥30,000/μL and ≥20,000/μL above baseline on at least 2 visits without a
dosing period–permitted rescue treatment in the previous 4 weeks and without any other previous rescue therapy.
|Timepoint(s) of evaluation of this end point
|Throughout the study. Please refer to protocol Appendix A and Appendix B.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The analyses for the clinical study report will be conducted after all patients randomized in the study have completed the end-of-study visit (ie, Week 32 for TAK-079 patients, Week 20 for placebo patients who chose not to enter the OLE, or EW32 for placebo patients who participated in the OLE)
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial months