low platelet count Primary immune thrombocytopenia
Conditions
Interventions
VAY736 (ianalumab) 3 or 9 mg/kg or placebo in addition to eltrombopag
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 18 years and older on the day of signing the informed consent. 2. A signed informed consent must be obtained prior to participation in the study. 3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy. 4. Patients with Platelet count below 30 G/L for whom eltrombopag is clinically indicated as per physician*s discretion and with no contraindication to receive eltrombopag.
Exclusion criteria
Exclusion criteria: 1. ITP patients who received second-line ITP treatments (other than corticosteroid therapy ± IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonists (TPO-RAs) for a limited time (max one week) before screening are eligible. 2. Patients with key lab abnormalities and patients with Evans syndrome or any other cytopenia (patients with low grade anemia related to bleeding or iron deficiency are eligible). 3. Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters 4. Patients with current or history of life-threatening bleeding 5. Patient that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), HBsAg positive are excluded. Participants who are hepatitis core antibody (HBcAb) positive are also executed unless all of the following criteria are met: HbsAg and HBV DNA are negative, participant has no pre existing liver fibrosis, hepatitis B monitoring is implemented , including regular ALT testing and HBV DNA testing. Antiviral prophylaxis with entecavir must be initiated prior randomization and must continue during the treatment period and at least 12 months after the last dose of ianalumab /placebo. If antiviral prophylaxis with entecavir is not allowed as per local guidelines or local clinical practice, clinically contraindicated or not accepted by the patient, participants who are HBsAg negative and HBcAb positive are not eligible. 6. Patients with known active or uncontrolled infection requiring systemic treatment during screening period. 7. Patients with hepatic impairment 8. Patients with concurrent coagulation disorders and/or receiving anti-platelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time from randomization to treatment failure defined as the time from randomization until : - platelet counts below 30 G/L), later than 8 weeks from randomization, - start of a new ITP treatment due to any reasons, need for a - rescue treatment (e.g.corticosteroids, IVIG, or platelet transfusion) later than 8 weeks from randomization, - ineligibility to taper or inability to discontinue eltrombopag - death (whatever the cause) Time to treatment failure (TTF) will be assessed in each treatment group and each of the two doses of ianalumab (ianalumab+eltrombopag) will be compared to the control arm (placebo+eltrombopag). | — |
Secondary
| Measure | Time frame |
|---|---|
| • Complete Response (CR) rate at each time point defined as the proportion of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment • Response rate at each timepoint defined as the proportion of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment • Complete Response (CR) rate at each time point defined as the proportion of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment • Response rate at each time point defined as the proportion of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment • Best response rate over all timepoints defined as proportion of participants with a best response of either response or complete response • Time from randomization to date of first response and time from randomization to date of first complete response • Duration of response is defined as the time from achievement of response to treatment failure • Duration of complete response(CR) is defined as the time from achievement of CR to loss of CR • Probability to be in treatment failure-free (as defined for the primary efficacy endpoint) at the end of the planned treatment period (end of Week 24) • Frequency of adverse events and other safety parameters • Number of severe infections and proportion of participants with severe infection • Proportion of participants with bleeding events according to WHO Bleeding Scale • Number and proportion of participants receiving rescue treatment • Change from baseline on total score of the PROMIS SF v1.0 Fatigue 13a • Change from baseline in ITP PAQ domain scores of Symptoms, Fatigue, Bother, Activity • B-cell levels: - Change from baseline in the frequency (% within the CD45) and absolute number of CD19+ B-cell counts - Time to first occurrence of B-cell recovery, defined as >=80% | — |
Countries
Netherlands
Outcome results
None listed