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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-503041-21-00 | Other Identifier | EU CTIS |
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The purpose of this study is to evaluate the therapeutic efficacy, safety and tolerability of ianalumab in adult patients with primary ITP previously treated with at least one corticosteroid and one TPO-RA.
This is a phase 2, open-label, single-arm study to evaluate the efficacy, safety and tolerability of ianalumab in participants with primary ITP (platelet count <30 G/L at screening) previously treated with at least a corticosteroid and a TPO-RA.
The study consists of the screening period, the primary endpoint assessment period, the follow-up period. The screening period will last for up to 14 days prior to the first dose of ianalumab. All eligible participants will be treated with the same dose of ianalumab and will complete the primary endpoint assessment period. After completion of the primary endpoint assessment period, all participants will continue in safety monitoring and those with a platelet count ≥30 G/L in absence of a new line of ITP therapy and rescue therapy will also continue in efficacy monitoring. The trial includes an option to offer a second course of ianalumab treatment to participants who achieved confirmed response during the initial course of ianalumab and later lost response to explore the benefit of the second course of treatment. The study will end once all participants have completed 24 months of safety follow-up since their last dose of ianalumab (including the optional second course of ianalumab treatment),or discontinued the study earlier.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single-arm | Experimental | All eligible participants will receive ianalumab at the same dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ianalumab | Biological | Intravenous infusion, prepared from concentrate solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Confirmed response | Confirmed response is defined as a platelet count of equal or above 50 G/L at two (or more) consecutive assessments at least 7 days apart, in the absence of:
| Between Week 1 Day 1 and Week 25 Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to confirmed response | Time from the first administration of ianalumab to the first assessment in the first sequence of two (or more) platelet assessments meeting the criteria of a confirmed response as defined by the primary endpoint. | From Week 1 Day 1 to Week 25 Day 1 |
| Duration of confirmed response |
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Inclusion Criteria:
Signed informed consent obtained prior to participation in the study.
Male or female participants aged 18 years and older on the day of signing informed consent.
Confirmed diagnosis of primary ITP.
At last ITP treatment, loss of response, insufficient response, no response or intolerance.
Platelet count <30 G/L and assessed as needing treatment (per physician's discretion) at screening. If concomitant ITP medication is clinically indicated, the platelet assessment showing a value <30 G/L must be performed after at least 14 days on a stable dose of a corticosteroid or/and a TPO-RA (less than 10% variation from current dose) and continue stable thereafter.
Key exclusion criteria:
Diagnosis of secondary thrombocytopenia.
Platelet or whole blood transfusion, plasmapheresis, or use of any other rescue medications within 14 days before first ianalumab infusion.
Participants with the following conditions at screening:
Treatment with a B-cell depleting therapy (e.g., rituximab) or anti-B-cell Activating Factor of the TNF Family (BAFF) (e.g., belimumab) within 12 weeks prior to the first administration of ianalumab.
Immunosuppressant drugs other than corticosteroids within 5 times the elimination half-life of the drug or 14 days before first ianalumab infusion, whichever is longer.
Prior splenectomy.
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Beth Israel Deaconess Med Center |
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Time from the first assessment in the first sequence of two (or more) platelet assessments meeting the criteria of a confirmed response to loss of response; with loss of response defined as the first of the following events:
|
| From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Complete Response rate at each timepoint | Percentage of participants with a platelet count of at least 100 G/L in the absence of rescue treatment/new ITP treatment. | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Response rate at each timepoint | Percentage of participants with a platelet count of at least 50 G/L in the absence of rescue treatment/new ITP treatment. | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Stable response at 6 months | Percentage of participants with at least 75% of platelet counts collected at month 6 (between study days 121 and 183) equal to or above 50 G/L in the absence of rescue treatment/new ITP treatment. | At 6 months |
| Stable response at 1 year | Percentage of participants with at least 66% of platelet counts collected at year 1 (between study days 296 and 379) equal to or above 50 G/L in the absence of rescue treatment/new ITP treatment. | At 1 year |
| Bleeding events according to the Modified World Health Organization (WHO) bleeding scale | Number of participants reporting bleeding events for each grade of the World Health Organization (WHO) bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal. | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Percentage of participants with bleeding events according to the Modified World Health Organization (WHO) bleeding scale | Percentage of participants reporting bleeding events for each grade of the WHO bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal. | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Number of participants who received rescue treatment | Number of participants who required rescue treatment | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Percentage of participants who received rescue treatment | Percentage of participants who required rescue treatment | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Change from baseline in the frequency of CD19+ B-cell counts | Post-baseline frequency of CD19+ B-cell counts compared to baseline | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Change from baseline in the absolute number of CD19+ B-cell counts | Post-baseline absolute number of CD19+ B-cell counts compared to baseline | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Time to first occurrence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL | Time to B-cell recovery defined as ≥80% of baseline or ≥50 cells/µL | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Change from baseline in immunoglobulins | Post-baseline immunoglobulin levels (change in titers of Total Ig, IgG, IgM, IgA) compared to baseline | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Incidence of anti-ianalumab antibodies in serum (ADA assay) over time | Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab | Up to 20 weeks after last dose of ianalumab |
| Titer of anti-ianalumab antibodies in serum (ADA assay) over time | Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab | Up to 20 weeks after last dose of ianalumab |
| Ianalumab serum concentrations over time | Ianalumab concentration in serum over time, including end of infusion and concentration at trough. | First dose (pre-dose, 2, 168, 336, 504, 672 hours post-dose); Subsequent doses (pre-dose and 2 hours post-dose); Last dose (pre-dose, 2 336, 672, 1344, 2016, 3360 hours post-dose) |
| Ianalumab serum PK: AUC concentrations over time | Ianalumab concentration in serum over time, including end of infusion and concentration at trough. | First dose (pre-dose, 2, 168, 336, 504, 672 hours post-dose); Subsequent doses (pre-dose and 2 hours post-dose); Last dose (pre-dose, 2 336, 672, 1344, 2016, 3360 hours post-dose) |
| Ianalumab serum PK parameters: Cmax | Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration | First dose (pre-dose, 2, 168, 336, 504, 672 hours post-dose); Subsequent doses (pre-dose and 2 hours post-dose); Last dose (pre-dose, 2 336, 672, 1344, 2016, 3360 hours post-dose) |
| Ianalumab serum PK parameters: Tmax | Time to reach maximum (peak) observed plasma, blood, serum or other body fluid drug concentration | First dose (pre-dose, 2, 168, 336, 504, 672 hours post-dose); Subsequent doses (pre-dose and 2 hours post-dose); Last dose (pre-dose, 2 336, 672, 1344, 2016, 3360 hours post-dose) |
| Confirmed response (CR) in the second course | Confirmed response is defined as a platelet count of equal or above 50 G/L at two (or more) consecutive assessments at least 7 days apart, in the absence of:
| Second course Week 1 Day1 to second course Week 25 Day1 |
| Time to confirmed response in the second course | two (or more) platelet assessments meeting the criteria of a confirmed response. | Second course Week 1 Day 1 to second course Week 25 Day 1 |
| Duration of confirmed response in the second course | Time from the first assessment, in the second course of two (or more) platelet assessments meeting the criteria of a confirmed response to loss of response; with loss of response defined as the first of the following events:
| Second course Week 1 Day 1 to second course Week 25 Day 1 |
| Response in the second course | Percentage of participants with a platelet count of at least 50 G/L in the absence of rescue treatment/new ITP treatment. | Second course Week 1 Day 1 to second course Week 25 Day 1 |
| Complete Response in the second course | Percentage of participants with a platelet count of at least 100 G/L in the absence of rescue treatment/new ITP treatment. | Second course Week 1 Day 1 to second course Week 25 Day 1 |
| Bleeding events in the second course according to the Modified World Health Organization (WHO) bleeding scale | Number of participants reporting bleeding events for each grade of the World Health Organization (WHO) bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal. | Second course Week 1 Day 1 to second course Week 25 Day 1 |
| Percentage of participants with bleeding events in the retreatment/second courseaccording to the Modified World Health Organization (WHO) bleeding scale | Percentage of participants reporting bleeding events for each grade of the WHO bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal. | Second course Week 1 Day 1 to second course Week 25 Day 1 |
| Number of Participants who received rescue treatment after second course | Number of participants who required rescue treatment | Second course Week 1 Day 1 to second course Week 25 Day 1 |
| Percentage of participants who received rescue treatment after receiving second course | Percentage of participants who required rescue treatment | Second course Week 1 Day 1 to second course Week 25 Day 1 |
| Titer of anti-ianalumab antibodies in serum (ADA assay) over time for second course | Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab | Second course Week 1 Day 1 until 20 weeks after last dose of ianalumab |
| Change from start of second course in immunoglobulins | Post-baseline immunoglobulin levels (change in titers of Total Ig, IgG, IgM, IgA) compared to retreatment baseline | From second course Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Change from start of second course in the absolute number of CD19+ B-cell counts | Post-baseline absolute number of CD19+ B-cell counts compared to baseline | From second course Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Change from start of second course to end of study in the absolute number of CD19+ B-cell counts | Post-baseline absolute number of CD19+ B-cell counts compared to baseline | From second course Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Time to first occurrence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL | Time to B-cell recovery defined as ≥80% of baseline or ≥50 cells/µL | From second course Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) |
| Ianalumab serum concentrations over time in the second course | Ianalumab concentration in serum over time, including end of infusion and concentration at trough. | First dose (pre-dose, 2, 168, 336, 504, 672 hours post-dose); Subsequent doses (pre-dose and 2 hours post-dose); Last dose (pre-dose, 2 336, 672, 1344, 2016, 3360 hours post-dose) in the second course |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Novartis Investigative Site | CABA | C1181ACH | Argentina |
| Novartis Investigative Site | Garran | Australian Capital Territory | 2605 | Australia |
| Novartis Investigative Site | Melbourne | Victoria | 3004 | Australia |
| Novartis Investigative Site | Wuhan | Hubei | 430022 | China |
| Novartis Investigative Site | Beijing | 100730 | China |
| Novartis Investigative Site | Jinan | 250012 | China |
| Novartis Investigative Site | Toulouse | 31059 | France |
| Novartis Investigative Site | Dresden | Saxony | 01307 | Germany |
| Novartis Investigative Site | Jena | Thuringia | 07740 | Germany |
| Novartis Investigative Site | Giessen | 35392 | Germany |
| Novartis Investigative Site | Torino | TO | 10126 | Italy |
| Novartis Investigative Site | Johor Bahru | 80100 | Malaysia |
| Novartis Investigative Site | Katowice | 40-519 | Poland |
| Novartis Investigative Site | Seoul | 06591 | South Korea |
| Novartis Investigative Site | Barcelona | Catalonia | 08003 | Spain |
| Novartis Investigative Site | Aydin | Efeler | 09100 | Turkey (Türkiye) |
| Novartis Investigative Site | Istanbul | Fatih | 34098 | Turkey (Türkiye) |
| Novartis Investigative Site | Edirne | Merkez | 22030 | Turkey (Türkiye) |
| Novartis Investigative Site | Izmir | 35100 | Turkey (Türkiye) |
| Novartis Investigative Site | Kocaeli | 41380 | Turkey (Türkiye) |
| Novartis Investigative Site | Glasgow | G31 2ER | United Kingdom |
| Novartis Investigative Site | London | W12 0HS | United Kingdom |
| ID | Term |
|---|---|
| D016553 | Purpura, Thrombocytopenic, Idiopathic |
| ID | Term |
|---|---|
| D011696 | Purpura, Thrombocytopenic |
| D011693 | Purpura |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D057049 | Thrombotic Microangiopathies |
| D013921 | Thrombocytopenia |
| D001791 | Blood Platelet Disorders |
| D000095542 | Cytopenia |
| D006474 | Hemorrhagic Disorders |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| C000656267 | ianalumab |
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