Clinical trial NCT05653219: A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Primary Immune Thrombocytopenia
Keywords: Primary immune thrombocytopenia (ITP),
ianalumab
VAY736
B-cell depletion
B-cell Activating Factor Receptor (BAFF-R) blockade
eltrombopag
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-12-16
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion criteria

1. Male or female patients aged 18 years and older on the day of signing the informed consent.
2. A signed informed consent must be obtained prior to participation in the study.
3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG.
4. 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

1. 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.
2. 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).
3. Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters
4. Patients with current or history of life-threatening bleeding
5. 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
6. Patients with known active or uncontrolled infection requiring systemic treatment during screening period
7. Patients with hepatic impairment
8. Patients with concurrent coagulation disorders and/or receiving antiplatelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (≤150 mg daily)
9. Nursing (breast feeding) or pregnant women

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Time from randomization until treatment failure
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
Secondary outcomes:
measure: Complete Response rate at each timepoint
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Response rate at each timepoint
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Best response rate across all timepoints
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Time to first response/time to first complete response
timeFrame: Time from randomization up to the longest observed treatment period duration
measure: Duration of response
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Stable response at 6 months
timeFrame: At 6 months
measure: Stable response at 1 year
timeFrame: At 1 year
measure: Duration of complete response
timeFrame: Randomization to end of study (up to 39 months after randomization of last participant)
measure: Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm
timeFrame: up to week 24
measure: Percentage of participants with bleeding events according to World Health Organization (WHO)
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Number of participants receiving rescue treatment
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Percentage of participants receiving rescue treatment
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Change from baseline in the frequency of CD19+ B-cell counts
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Change from baseline in the absolute number of CD19+ B-cell counts
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Change from baseline on T-score of the PROMIS SF v1.0 Fatigue 13a
timeFrame: From screening (baseline) until end of study (up 39 months after randomization of last participant)
measure: Change from baseline in ITP PAQ domain scores of symptoms, fatigue, bother (uncomfortable), activity
timeFrame: From screening (baseline) until end of study (up 39 months after randomization of last participant)
measure: Time to first occurence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: Change from baseline in immunoglobulins
timeFrame: Randomization to until end of study (up to 39 months after randomization of last participant)
measure: PK parameters: AUClast
timeFrame: 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)
measure: PK parameters: AUCtau
timeFrame: 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)
measure: PK parameters: Cmax
timeFrame: 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)
measure: PK parameters: Tmax
timeFrame: 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)
measure: PK parameters: Accumulation ratio Racc
timeFrame: After last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
measure: Incidence of anti-ianalumab antibodies in serum (ADA assay) over time
timeFrame: up to week 33
measure: Titer of anti-ianalumab antibodies in serum (ADA assay) over time
timeFrame: up to week 33
Other outcomes:
Locations:
city: Yuma
country: United States
facility: Yuma Regional Medical Center
state: Arizona
city: Aurora
country: United States
facility: University of Colorado Anschutz
state: Colorado
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Memorial Medical Center
state: Massachusetts
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: Billings
country: United States
facility: St Vincent Frontier Cancer Center
state: Montana
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Nyack
country: United States
facility: Hematology Oncology Association of Rockland
state: New York
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Ogden
country: United States
facility: Community Cancer Trials of Utah
state: Utah
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Roeselare
country: Belgium
facility: Novartis Investigative Site
city: Yvoir
country: Belgium
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Binzhou
country: China
facility: Novartis Investigative Site
state: Shandong
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Jinan
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Brno Bohunice
country: Czechia
facility: Novartis Investigative Site
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Blois Cedex
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Rishikesh
country: India
facility: Novartis Investigative Site
state: Uttarakhand
city: Kolkata
country: India
facility: Novartis Investigative Site
state: West Bengal
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Trieste
country: Italy
facility: Novartis Investigative Site
state: TS
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kofu-city
country: Japan
facility: Novartis Investigative Site
state: Yamanashi
city: Kumamoto
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Jeollanam
country: Korea, Republic of
facility: Novartis Investigative Site
city: Kota Kinabalu
country: Malaysia
facility: Novartis Investigative Site
state: Sabah
city: Subang Jaya
country: Malaysia
facility: Novartis Investigative Site
state: Selangor
city: Johor Bahru
country: Malaysia
facility: Novartis Investigative Site
city: Penang
country: Malaysia
facility: Novartis Investigative Site
city: Pulau Pinang
country: Malaysia
facility: Novartis Investigative Site
city: Selangor
country: Malaysia
facility: Novartis Investigative Site
city: Saltillo
country: Mexico
facility: Novartis Investigative Site
state: Coahuila
city: Morelia
country: Mexico
facility: Novartis Investigative Site
state: Michoacan
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo Leon
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
state: Zuid Holland
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Makati City
country: Philippines
facility: Novartis Investigative Site
city: Quezon
country: Philippines
facility: Novartis Investigative Site
city: Craiova
country: Romania
facility: Novartis Investigative Site
city: Timisoara
country: Romania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Aydin
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Samsun
country: Turkey
facility: Novartis Investigative Site
city: Truro
country: United Kingdom
facility: Novartis Investigative Site
state: Cornwall
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: