A Phase 3 Randomized, Double-blind Study of Ianalumab (VAY736) Versus Placebo in Addition to Eltrombopag in Patients With Primary Immune Thrombocytopenia (ITP) Who Had an Insufficient Response or Relapsed After First Line Steroid Treatment (VAYHIT2)
Overview
- Phase
- Phase 3
- Intervention
- Ianalumab
- Conditions
- Primary Immune Thrombocytopenia
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 152
- Locations
- 84
- Primary Endpoint
- Time from randomization until treatment failure
- Status
- Active, not recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the effect of two different doses of ianalumab added to eltrombopag to prolong Time to Treatment Failure (TTF) in adults with primary ITP who failed previous first-line treatment with steroids.
Detailed Description
This is a multicenter, randomized, double-blinded phase 3 study to assess efficacy and safety of two different doses of ianalumab versus placebo in addition to eltrombopag in adults with primary ITP (platelet count \<30 G/L) who failed previous first-line treatment with corticosteroids. After completion of the screening period, the participants will enter the randomized treatment period (ianalumab/placebo with eltrombopag) followed by the eltrombopag tapering period. Afterwards, all participants will enter the follow-up period to be monitored for efficacy and safety or safety only depending on how the participants responded to the study treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients aged 18 years and older on the day of signing the informed consent.
- •A signed informed consent must be obtained prior to participation in the study.
- •A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG.
- •Patient with platelet count \<30G/L (whom eltrombopag is clinically indicated as per physician's discretion) and with no contraindication to receive eltrombopag
Exclusion Criteria
- •ITP patients who received second-line ITP treatments (other than steroid therapy± IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonists (TPO-RAs) for a limited time (max one week) before screening are eligible.
- •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).
- •Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters
- •Patients with current or history of life-threatening bleeding
- •Patient that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B surface Antigen (HBsAg)/ Hepatitis B core antibody (HBcAb)-positive. HBcAb-positive patients can be enrolled if HBsAg negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given
- •Patients with known active or uncontrolled infection requiring systemic treatment during screening period
- •Patients with hepatic impairment
- •Patients with concurrent coagulation disorders and/or receiving antiplatelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (≤150 mg daily)
- •Nursing (breast feeding) or pregnant women
- •Other protocol-defined inclusion/exclusion criteria may apply.
Arms & Interventions
Treatment arm 1
Participants will receive eltrombopag and ianalumab lower dose
Intervention: Ianalumab
Treatment arm 1
Participants will receive eltrombopag and ianalumab lower dose
Intervention: Eltrombopag
Treatment arm 2
Participants will receive eltrombopag and ianalumab higher dose
Intervention: Ianalumab
Treatment arm 2
Participants will receive eltrombopag and ianalumab higher dose
Intervention: Eltrombopag
Treatment arm 3
Participants will receive eltrombopag and placebo
Intervention: Eltrombopag
Treatment arm 3
Participants will receive eltrombopag and placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Time from randomization until treatment failure
Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant)
Time from randomization until treatment failure is defined as the time from randomization date until the first of the following events indicative of treatment failure: * platelet count below 30 G/L * start of a new ITP treatment * need for a rescue treatment * ineligibility to taper or inability to discontinue eltrombopag * death
Secondary Outcomes
- Stable response at 6 months(At 6 months)
- Complete Response rate at each timepoint(Randomization to until end of study (up to 39 months after randomization of last participant))
- Response rate at each timepoint(Randomization to until end of study (up to 39 months after randomization of last participant))
- Best response rate across all timepoints(Randomization to until end of study (up to 39 months after randomization of last participant))
- Time to first response/time to first complete response(Time from randomization up to the longest observed treatment period duration)
- Duration of response(Randomization to until end of study (up to 39 months after randomization of last participant))
- Stable response at 1 year(At 1 year)
- Duration of complete response(Randomization to end of study (up to 39 months after randomization of last participant))
- Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm(up to week 24)
- Percentage of participants with bleeding events according to World Health Organization (WHO)(Randomization to until end of study (up to 39 months after randomization of last participant))
- Number of participants receiving rescue treatment(Randomization to until end of study (up to 39 months after randomization of last participant))
- Percentage of participants receiving rescue treatment(Randomization to until end of study (up to 39 months after randomization of last participant))
- Change from baseline in the frequency of CD19+ B-cell counts(Randomization to until end of study (up to 39 months after randomization of last participant))
- Change from baseline in the absolute number of CD19+ B-cell counts(Randomization to until end of study (up to 39 months after randomization of last participant))
- Change from baseline on T-score of the PROMIS SF v1.0 Fatigue 13a(From screening (baseline) until end of study (up 39 months after randomization of last participant))
- Change from baseline in ITP PAQ domain scores of symptoms, fatigue, bother (uncomfortable), activity(From screening (baseline) until end of study (up 39 months after randomization of last participant))
- Time to first occurence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL(Randomization to until end of study (up to 39 months after randomization of last participant))
- Change from baseline in immunoglobulins(Randomization to until end of study (up to 39 months after randomization of last participant))
- PK parameters: AUClast(After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose))
- PK parameters: AUCtau(After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose))
- PK parameters: Cmax(After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose))
- PK parameters: Tmax(After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose))
- PK parameters: Accumulation ratio Racc(After last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose))
- Incidence of anti-ianalumab antibodies in serum (ADA assay) over time(up to week 33)
- Titer of anti-ianalumab antibodies in serum (ADA assay) over time(up to week 33)
- Stable response at 6 months (Key Secondary Endpoint)(At 6 months)