A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids
- Conditions
- Primary Immune Thrombocytopenia
- Interventions
- Registration Number
- NCT05653219
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 152
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment arm 2 Ianalumab Participants will receive eltrombopag and ianalumab higher dose Treatment arm 3 Placebo Participants will receive eltrombopag and placebo Treatment arm 2 Eltrombopag Participants will receive eltrombopag and ianalumab higher dose Treatment arm 1 Eltrombopag Participants will receive eltrombopag and ianalumab lower dose Treatment arm 3 Eltrombopag Participants will receive eltrombopag and placebo Treatment arm 1 Ianalumab Participants will receive eltrombopag and ianalumab lower dose
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 Stable response at 6 months
Stable response at 6 months At 6 months Percentage of participants with at least 3 platelet count collected at month 6 between (study days 121 and 183 and at least 75% of platelet counts qualified as a response
Stable response at 1 year At 1 year Percentage of participants with at least 2 platelet count collected at year 1 between (study days 296 and 379 and at least 66% of platelet counts qualified as a response
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 stable response at 1 year period
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 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) 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, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 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, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 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, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 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, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 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, EOI, 336, 672, 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
Trial Locations
- Locations (12)
Yuma Regional Medical Center
🇺🇸Yuma, Arizona, United States
University of Colorado Anschutz
🇺🇸Aurora, Colorado, United States
NorthShore University Health System
🇺🇸Evanston, Illinois, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
UMASS Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Michigan Center of Medical Research
🇺🇸Farmington Hills, Michigan, United States
St Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Hematology Oncology Association of Rockland
🇺🇸Nyack, New York, United States
Texas Oncology
🇺🇸Dallas, Texas, United States
Community Cancer Trials of Utah
🇺🇸Ogden, Utah, United States
Novartis Investigative Site
🇬🇧Oxford, United Kingdom