Primary Immune Thrombocytopenia (ITP)
Conditions
Keywords
Primary Immune Thrombocytopenia, ITP, VAY736, ianalumab, first-line corticosteroid treatment, eltrombopag, Pediatric patients
Brief summary
The purpose of this study is to assess the efficacy, safety and pharmacokinetics (PK) of ianalumab (VAY736) in addition to eltrombopag treatment; and to inform the dose of ianalumab in pediatric patients (5 to \<18 years of age) with primary ITP who have had an insufficient response to or relapsed after first-line treatment with corticosteroids.
Detailed description
The study will consist of 3 phases: * Screening phase * Treatment phase * Follow-up phase consisting of Efficacy follow-up phase and Safety follow-up phase
Interventions
BIOLOGICALIanalumab
Liquid in a vial Concentrate for solution for infusion
DRUGEltrombopag
Film-coated tablet and also Powder for oral suspension
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent and/or assent must be obtained from the participant and/or their parent(s)/legal guardian(s) before any study-related activity or assessment is performed. Informed consent must be obtained from participants once they reach the local legal age of adulthood during the study. * Male or female patients aged 5 to \<18 years on the day of signing informed assent/consent (as appropriate for age). * A confirmed diagnosis of primary ITP, with insufficient response to, or relapse after a firstline corticosteroid therapy with or without IVIG. * Patients with platelet count \<30 G/L for whom eltrombopag is clinically indicated (per physician's discretion) and with no contraindications to receive eltrombopag. * Patients who are up-to-date on childhood vaccinations as per the local recommended vaccination schedule.
Exclusion criteria
* Patients with ITP who received previous second-line ITP treatments (other than corticosteroid therapy with or without IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonists (TPO-RAs) for a limited time (maximum one week) before or during screening are eligible. * Patients with key renal or hepatic laboratory abnormalities. * Patients with other hematologic diagnosis associated with cytopenias, including Evans Syndrome. * Patients with current or history of life-threatening bleeding due to thrombocytopenia. * Patients who are Human Immunodeficiency Virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) positive. * Patients with known active or uncontrolled infections requiring systemic treatment during the screening period or history of recurrent clinically significant infection. * Patients with hepatic impairment (Child-Pugh score \>5, or equivalent). * Patients with concurrent bleeding disorders or coagulation disorders and/or receiving antiplatelet or anticoagulant medication. * Female patients who are nursing or pregnant. Other protocol-defined inclusion/exclusion may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to treatment failure (TTF) | enrolled until end of study (up to 39 months from the last patient enrolled) | TTF is defined as the time from start of treatment until any of a list of specific events is met. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stable response rate at 6 months (SR-6) | 6 months | SR-6 is defined as the percentage of participants with a platelet count of at least 50 G/L at 75% of the measures taken between Study Day 121 and 183, in the absence of rescue or new Immune Thrombocytopenia (ITP) therapy. |
| Stable response rate at 12 months (SR-12) | 12 months | SR-12 is defined as the percentage of participants with a platelet count of at least 50 G/L at 66% of the measures taken between Study Day 296 and 379, in the absence of rescue or new ITP therapy. |
| Complete Response (CR) rate | from enrollment until end of study (up to 39 months from the last patient enrolled) | CR is defined as the percentage of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment. |
| Response Rate (RR) | from enrollment until end of study (up to 39 months from the last patient enrolled) | RR is defined as the percentage of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment. |
| Time to response | from enrollment until end of study (up to 39 months from the last patient enrolled) | Time to response is defined as the time from the start of treatment to the date of the first response. |
| Time to complete response | from enrollment until end of study (up to 39 months from the last patient enrolled) | Time to complete response is defined as the time from the start of treatment to the date of complete response. |
| Duration of response | from enrollment until end of study (up to 39 months from the last patient enrolled) | Duration of response is defined as the time from achievement of response (platelet count ≥ 50 G/L) to treatment failure. |
| Duration of complete response | from enrollment until end of study (up to 39 months from the last patient enrolled) | Duration of complete response is defined as the time from achievement of response to loss of complete response. |
| Bleeding Events | from enrollment until end of study (up to 39 months from the last patient enrolled) | Percentage of participants with bleeding events according to WHO Bleeding Scale |
| Rescue medication | from enrollment until end of study (up to 39 months from the last patient enrolled) | Number and percentage of participants receiving rescue treatment |
| Rate of participants who successfully taper and discontinue eltrombopag - being treatment failure-free | End of Week 24 | Treatment failure-free (as defined for the primary efficacy endpoint) at the end of the planned Treatment period. |
| Ianalumab serum concentration (Cmax) | at pre-dose of each of the 4 dosing events and end-of-infusion and first and last dose | Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body. |
| B cell levels: Change from baseline in the frequency (% within CD45+ cells) and absolute number of CD19+ B cells | 12 months after the first treatment of the last enrolled participant, final dbl: until end of study (up to 39 months from the last patient enrolled) | Number and percentage of B-cell levels in the blood, and comparison with baseline levels of B-cells at specific timepoints. |
| B cell levels: Time to first occurrence of B cell recovery | 12 months after the first treatment of the last enrolled participant, final dbl: until end of study (up to 39 months from the last patient enrolled) | Time to first occurrence of B cell recovery is defined as ≥80% of baseline or ≥50 cells/μL. |
| Immunoglobulins: Change from baseline in immunoglobulin levels | 12 months after the first treatment of the last enrolled participant, final dbl: until end of study (up to 39 months from the last patient enrolled) | Change from baseline levels of serum immunoglobulins at specific timepoints. |
| Platelet counts: Change from baseline in platelet count | 12 months after the first treatment of the last enrolled participant, final dbl: until end of study (up to 39 months from the last patient enrolled) | Change from baseline levels of platelets at specific timepoints. |
| Incidence and titer of anti-ianalumab antibodies in serum (anti-drug-antibody (ADA) assay) | over time (up to 39 months from the last patient enrolled) | Anti-drug antibodies (ADAs) are immune responses developed by a participant's body against biologic or gene therapies. |
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed