VAYHIT2: A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment arm 1 Participants will receive eltrombopag and ianalumab lower dose |
Biological: Ianalumab
Concentrate for solution for infusion for intravenous use
Other Names:
Drug: Eltrombopag
Film-coated tablet for oral use
Other Names:
|
| Experimental: Treatment arm 2 Participants will receive eltrombopag and ianalumab higher dose |
Biological: Ianalumab
Concentrate for solution for infusion for intravenous use
Other Names:
Drug: Eltrombopag
Film-coated tablet for oral use
Other Names:
|
| Placebo Comparator: Treatment arm 3 Participants will receive eltrombopag and placebo |
Drug: Eltrombopag
Film-coated tablet for oral use
Other Names:
Drug: Placebo
Concentrate for solution for infusion for intravenous use.
|
Outcome Measures
Primary Outcome Measures
- Time from randomization until treatment failure [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 Outcome Measures
- Complete Response rate at each timepoint [Randomization to until end of study (up to 39 months after randomization of last participant)]
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 at each timepoint [Randomization to until end of study (up to 39 months after randomization of last participant)]
Percentage 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 across all timepoints [Randomization to until end of study (up to 39 months after randomization of last participant)]
Percentage of participants with a best response rate of either response or complete response
- Time to first response/time to first complete response [Time from randomization up to the longest observed treatment period duration]
Time from randomization to date of first response and time from randomization to date of first complete response
- Duration of response [Randomization to until end of study (up to 39 months after randomization of last participant)]
Time from achievement of response to treatment failure
- Duration of complete response [Randomization to end of study (up to 39 months after randomization of last participant)]
Time from achievement of complete response to loss of complete response
- Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm [up to week 24]
Probability to be treatment failure-free (as defined for the primary efficacy endpoint)
- 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)]
Percentage of participants reporting bleeding events according to WHO bleeding scale
- Number of participants receiving rescue treatment [Randomization to until end of study (up to 39 months after randomization of last participant)]
Number of participants who are in need of rescue treatment in each treatment arm
- Percentage of participants receiving rescue treatment [Randomization to until end of study (up to 39 months after randomization of last participant)]
Percentage of participants who are in need of rescue treatment
- 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)]
Post-baseline frequency of CD19+ B-cell counts (percentage within CD45) compared to baseline
- 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)]
Post-baseline absolute number of CD19+ B-cell counts compared to baseline
- Change from baseline on total score of the PROMIS SF v1.0 Fatigue 13a [From screening (baseline) until end of study (up 39 months after randomization of last participant)]
The Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a includes 13 items that assess fatigue in adults.
- 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)]
The ITP-PAQ is a 44 item scale for measuring HRQoL in adults with ITP across ten scales: Symptoms, Bother-Physical Health, Fatigue/Sleep, Activity, Fear, Psychological Health, Work, Social Activity, Women´s Reproductive Health, overall QoL. Each item is rated on a Likert type scale. Each scale is scored from 0 to 100. Higher scores represent better HRQoL.
- 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)]
Time to B-cell recovery defined as ≥80% of baseline or ≥50 cells/µL
- Change from baseline in immunoglobulins [Randomization to until end of study (up to 39 months after randomization of last participant)]
Change from baseline in immunoglobulin levels
- PK parameters: AUClast [After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)]
AUClast: Area under the curve from time zero to the last measurable concentration sampling time (tlast)
- PK parameters: AUCtau [After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)]
AUCtau: Area under the curve calculated to the end of a dosing interval (tau)
- PK parameters: Cmax [After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)]
Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration
- PK parameters: Tmax [After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)]
Time to reach maximum (peak) observed plasma, blood, serum or other body fluid drug concentration
- PK parameters: Accumulation ratio Racc [After last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)]
Accumulation ratio calculated using AUC values obtained after the last and first dose
- Incidence of anti-ianalumab antibodies in serum (ADA assay) over time [up to week 33]
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab
- Titer of anti-ianalumab antibodies in serum (ADA assay) over time [up to week 33]
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab
Eligibility Criteria
Criteria
Key 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.
-
Platelet count <30 G/L and assessed need for treatment (per physician's discretion).
Key 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 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
-
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
-
Female patients who are pregnant or nursing
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Singapore | Singapore | 119228 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CVAY736Q12301