Un estudio de eficacia y seguridad de ianalumab versus placebo además de eltrombopag en pacientes con trombocitopenia inmunitaria primaria que no respondieron a los esteroides (VAYHIT2)
Un estudio de fase 3, aleatorizado, doble ciego de ianalumab (VAY736) versus placebo además de eltrombopag en pacientes con trombocitopenia inmunitaria primaria (ITP) que tuvieron una respuesta insuficiente o recayeron después del tratamiento con esteroides de primera línea (VAYHIT2)
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Dresden, Alemania, 01307
- Novartis Investigative Site
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North Rhine-Westphalia
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Cologne, North Rhine-Westphalia, Alemania, 50937
- Novartis Investigative Site
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Saxony
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Dresden, Saxony, Alemania, 01307
- Novartis Investigative Site
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Thuringia
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Jena, Thuringia, Alemania, 07740
- Novartis Investigative Site
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CABA, Argentina, C1181ACH
- Novartis Investigative Site
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Vienna, Austria, 1090
- Novartis Investigative Site
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Namur
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Yvoir, Namur, Bélgica, 5530
- Novartis Investigative Site
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West Vlaanderen
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Roeselare, West Vlaanderen, Bélgica, 8800
- Novartis Investigative Site
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Brno, Chequia, 625 00
- Novartis Investigative Site
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Prague, Chequia, 128 08
- Novartis Investigative Site
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Prague, Chequia, 100 34
- Novartis Investigative Site
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Jeollanam, Corea del Sur, 519763
- Novartis Investigative Site
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Seoul, Corea del Sur, 06591
- Novartis Investigative Site
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Salamanca, España, 37007
- Novartis Investigative Site
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A Coruna
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Santiago Compostela, A Coruna, España, 15706
- Novartis Investigative Site
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Arizona
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Yuma, Arizona, Estados Unidos, 85364
- Yuma Regional Medical Center
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- University of Colorado Anschutz
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Illinois
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Evanston, Illinois, Estados Unidos, 60201
- Endeavor Health
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Boston Medical Center
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Worcester, Massachusetts, Estados Unidos, 01665
- UMASS Memorial Medical Center
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Michigan
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Farmington Hills, Michigan, Estados Unidos, 48334
- Michigan Center of Medical Research
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Montana
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Billings, Montana, Estados Unidos, 59102
- St Vincent Frontier Cancer Center
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New York
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Nyack, New York, Estados Unidos, 10960
- Hematology Oncology Association of Rockland
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The Bronx, New York, Estados Unidos, 10461
- Montefiore Medical Center
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Makati City, Filipinas, 1229
- Novartis Investigative Site
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Quezon, Filipinas, 1102
- Novartis Investigative Site
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Blois, Francia, 41000
- Novartis Investigative Site
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Le Mans, Francia, 72000
- Novartis Investigative Site
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Budapest, Hungría, 1083
- Novartis Investigative Site
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Hajdu Bihar Megye
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Debrecen, Hajdu Bihar Megye, Hungría, 4032
- Novartis Investigative Site
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Uttarakhand
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Rishikesh, Uttarakhand, India, 249203
- Novartis Investigative Site
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West Bengal
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Kolkata, West Bengal, India, 700014
- Novartis Investigative Site
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BO
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Bologna, BO, Italia, 40138
- Novartis Investigative Site
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RM
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Roma, RM, Italia, 00168
- Novartis Investigative Site
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Roma, RM, Italia, 00133
- Novartis Investigative Site
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TS
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Trieste, TS, Italia, 34129
- Novartis Investigative Site
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Kumamoto, Japón, 8600008
- Novartis Investigative Site
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Aichi-ken
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Nagoya, Aichi-ken, Japón, 4538511
- Novartis Investigative Site
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Osaka
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Osaka, Osaka, Japón, 5400006
- Novartis Investigative Site
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Suita, Osaka, Japón, 5650871
- Novartis Investigative Site
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Yamanashi
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Kofu, Yamanashi, Japón, 4008506
- Novartis Investigative Site
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George Town, Malasia, 10050
- Novartis Investigative Site
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Johor Bahru, Malasia, 80100
- Novartis Investigative Site
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Kuala Selangor, Malasia, 68000
- Novartis Investigative Site
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Pulau Pinang
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George Town, Pulau Pinang, Malasia, 10450
- Novartis Investigative Site
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Sabah
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Kota Kinabalu, Sabah, Malasia, 88586
- Novartis Investigative Site
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Selangor
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Subang Jaya, Selangor, Malasia, 47500
- Novartis Investigative Site
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Coahuila
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Saltillo, Coahuila, México, 25230
- Novartis Investigative Site
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Michoacán
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Morelia, Michoacán, México, 58260
- Novartis Investigative Site
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Nuevo León
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Monterrey, Nuevo León, México, 64460
- Novartis Investigative Site
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Utrecht, Países Bajos, 3584 CX
- Novartis Investigative Site
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South Holland
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Leiden, South Holland, Países Bajos, 2333 ZA
- Novartis Investigative Site
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Beijing, Porcelana, 100730
- Novartis Investigative Site
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Jinan, Porcelana, 250012
- Novartis Investigative Site
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Tianjin, Porcelana, 300020
- Novartis Investigative Site
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Guangdong
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Guangzhou, Guangdong, Porcelana, 510515
- Novartis Investigative Site
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Hubei
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Wuhan, Hubei, Porcelana, 430022
- Novartis Investigative Site
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Shandong
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Binzhou, Shandong, Porcelana, 256603
- Novartis Investigative Site
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Zhejiang
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Hangzhou, Zhejiang, Porcelana, 310003
- Novartis Investigative Site
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London, Reino Unido, W12 0HS
- Novartis Investigative Site
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London, Reino Unido, E1 1BB
- Novartis Investigative Site
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Oxford, Reino Unido, OX3 7LE
- Novartis Investigative Site
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Timișoara, Rumania, 300079
- Novartis Investigative Site
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Dolj
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Craiova, Dolj, Rumania, 200136
- Novartis Investigative Site
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Singapore, Singapur, 119074
- Novartis Investigative Site
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Singapore, Singapur, 169608
- Novartis Investigative Site
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Bangkok, Tailandia, 10700
- Novartis Investigative Site
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Chiang Mai, Tailandia, 50200
- Novartis Investigative Site
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Taoyuan, Taiwán, 33305
- Novartis Investigative Site
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Izmir, Turquía (Türkiye), 35100
- Novartis Investigative Site
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Atakum
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Samsun, Atakum, Turquía (Türkiye), 55200
- Novartis Investigative Site
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Bilkent Cankaya
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Ankara, Bilkent Cankaya, Turquía (Türkiye), 06800
- Novartis Investigative Site
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Efeler
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Aydin, Efeler, Turquía (Türkiye), 09100
- Novartis Investigative Site
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Fatih
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Istanbul, Fatih, Turquía (Türkiye), 34098
- Novartis Investigative Site
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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.
- Patient with platelet count <30G/L (whom eltrombopag is clinically indicated as per physician's discretion) and with no contraindication to receive eltrombopag
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 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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Treatment arm 1 - Lower dose
Participants will receive eltrombopag and ianalumab lower dose |
Concentrate for solution for infusion for intravenous use
Otros nombres:
Film-coated tablet for oral use
Otros nombres:
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Experimental: Treatment arm 2 - Higher dose
Participants will receive eltrombopag and ianalumab higher dose |
Concentrate for solution for infusion for intravenous use
Otros nombres:
Film-coated tablet for oral use
Otros nombres:
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Comparador de placebos: Treatment arm 3 - Placebo
Participants will receive eltrombopag and placebo |
Film-coated tablet for oral use
Otros nombres:
Concentrate for solution for infusion for intravenous use. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Time from randomization until treatment failure
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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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:
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Randomization to until end of study (up to 39 months after randomization of last participant)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Stable response at 6 months (Key Secondary Endpoint)
Periodo de tiempo: At 6 months
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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). |
At 6 months
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Complete Response rate at each timepoint
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Percentage of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Response rate at each timepoint
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Percentage of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Best response rate across all timepoints
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Percentage of participants with a best response rate of either response or complete response |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Time to first response/time to first complete response
Periodo de tiempo: Time from randomization up to the longest observed treatment period duration
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Time from randomization to date of first response and time from randomization to date of first complete response |
Time from randomization up to the longest observed treatment period duration
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Duration of response
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Time from achievement of response to treatment failure. |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Stable response at 1 year
Periodo de tiempo: At 1 year
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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). |
At 1 year
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Duration of complete response
Periodo de tiempo: Randomization to end of study (up to 39 months after randomization of last participant)
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Time from achievement of complete response to loss of complete response stable response at 1 year period |
Randomization to end of study (up to 39 months after randomization of last participant)
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Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm
Periodo de tiempo: up to week 24
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Probability to be treatment failure-free (as defined for the primary efficacy endpoint) |
up to week 24
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Percentage of participants with bleeding events according to World Health Organization (WHO)
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Percentage of participants reporting bleeding events according to WHO bleeding scale |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Number of participants receiving rescue treatment
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Number of participants who are in need of rescue treatment in each treatment arm |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Percentage of participants receiving rescue treatment
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Percentage of participants who are in need of rescue treatment |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Change from baseline in the frequency of CD19+ B-cell counts
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Post-baseline frequency of CD19+ B-cell counts (percentage within CD45) compared to baseline |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Change from baseline in the absolute number of CD19+ B-cell counts
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
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Post-baseline absolute number of CD19+ B-cell counts compared to baseline |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Change from baseline on T-score of the PROMIS SF v1.0 Fatigue 13a
Periodo de tiempo: From screening (baseline) until end of study (up 39 months after randomization of last participant)
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The Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a includes 13 items that assess fatigue in adults. |
From screening (baseline) until end of study (up 39 months after randomization of last participant)
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Change from baseline in ITP PAQ domain scores of symptoms, fatigue, bother (uncomfortable), activity
Periodo de tiempo: 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. |
From screening (baseline) until end of study (up 39 months after randomization of last participant)
|
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Time to first occurence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL
Periodo de tiempo: 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 |
Randomization to until end of study (up to 39 months after randomization of last participant)
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Change from baseline in immunoglobulins
Periodo de tiempo: Randomization to until end of study (up to 39 months after randomization of last participant)
|
Change from baseline in immunoglobulin levels |
Randomization to until end of study (up to 39 months after randomization of last participant)
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|
PK parameters: AUClast
Periodo de tiempo: 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) |
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
Periodo de tiempo: 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) |
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)
|
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PK parameters: Cmax
Periodo de tiempo: 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 |
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
Periodo de tiempo: 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 |
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
Periodo de tiempo: 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 |
After last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
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Incidence of anti-ianalumab antibodies in serum (ADA assay) over time
Periodo de tiempo: up to week 33
|
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab |
up to week 33
|
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Titer of anti-ianalumab antibodies in serum (ADA assay) over time
Periodo de tiempo: up to week 33
|
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab |
up to week 33
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Citopenia
- Procesos Patológicos
- Enfermedades autoinmunes
- Enfermedades del sistema inmunológico
- Hemorragia
- Manifestaciones de la piel
- Enfermedades hematológicas
- Trastornos de la coagulación de la sangre
- Trastornos hemorrágicos
- Trastornos de las plaquetas sanguíneas
- Microangiopatías trombóticas
- Púrpura Trombocitopénica
- Púrpura
- Trombocitopenia
- Condiciones Patológicas, Signos y Síntomas
- Signos y síntomas
- Enfermedades hemic y linfáticas
- Púrpura Trombocitopénica Idiopática
- Eltrombopag
- Ianalumab
Otros números de identificación del estudio
- CVAY736Q12301
- 2024-512890-28-00 (Otro identificador: EU CTIS)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
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
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .