A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids

Primary Immune Thrombocytopenia Clinical Trial

— VAYHIT2  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05653219
• Other study ID #: CVAY736Q12301
• Status: Recruiting
• Phase: Phase 3
• Start date: January 21, 2023
• Est. completion date: May 19, 2028

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: May 19, 2028
• Est. primary completion date: June 6, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Female patients who are pregnant or nursing Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Primary Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Biological:
• Ianalumab
Concentrate for solution for infusion for intravenous use

Drug:
• Eltrombopag
Film-coated tablet for oral use
• Placebo
Concentrate for solution for infusion for intravenous use.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Parkville	Victoria
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wels
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Roeselare
Belgium	Novartis Investigative Site	Yvoir
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Binzhou	Shandong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Ji Nan
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Wuhan	Hubei
Czechia	Novartis Investigative Site	Brno Bohunice	Czech Republic
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 10
France	Novartis Investigative Site	Blois Cedex
France	Novartis Investigative Site	Le Mans	Cedex 09
France	Novartis Investigative Site	Vandoeuvre Les Nancy
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Giessen
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Koeln
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
India	Novartis Investigative Site	Chandigarh
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Rishikesh	Uttarakhand
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Trieste	TS
Italy	Novartis Investigative Site	Vicenza	VI
Japan	Novartis Investigative Site	Aomori
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Hiroshima
Japan	Novartis Investigative Site	Kofu-city	Yamanashi
Japan	Novartis Investigative Site	Kumamoto-city	Kumamoto
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Narita	Chiba
Japan	Novartis Investigative Site	Omura	Nagasaki
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Suita	Osaka
Korea, Republic of	Novartis Investigative Site	Jeollanam
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Malaysia	Novartis Investigative Site	Johor Bahru
Malaysia	Novartis Investigative Site	Kota Kinabalu	Sabah
Malaysia	Novartis Investigative Site	Kuala Lumpur	MYS
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Penang
Malaysia	Novartis Investigative Site	Pulau Pinang
Malaysia	Novartis Investigative Site	Selangor
Malaysia	Novartis Investigative Site	Subang Jaya	Selangor
Netherlands	Novartis Investigative Site	Utrecht
Norway	Novartis Investigative Site	Gralum
Philippines	Novartis Investigative Site	Makati City
Philippines	Novartis Investigative Site	Quezon
Romania	Novartis Investigative Site	Bucharest	District 2
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Craiova
Romania	Novartis Investigative Site	Sibiu
Romania	Novartis Investigative Site	Timisoara
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Murcia
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	Santiago De Compostela	Galicia
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Edirne
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Samsun
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Truro	Cornwall
United States	St Vincent Frontier Cancer Center .	Billings	Montana
United States	Montefiore Medical Center .	Bronx	New York
United States	Uni of Chi Medi Ctr Hema and Onco Main Centre	Chicago	Illinois
United States	Community Cancer Institute	Clovis	California
United States	Texas Oncology Drug Ship 5	Dallas	Texas
United States	STAT Research Inc Premier Clin Res LLC STAT Res	Dayton	Ohio
United States	NorthShore University Health System	Evanston	Illinois
United States	Compassionate Care Res Group Inc	Fountain Valley	California
United States	Center of Clnl Rsch and Innovation	Houston	Texas
United States	Clinical Research Alliance Research	Lake Success	New York
United States	Napa Research	Margate	Florida
United States	Hematology Oncology Association of Rockland	Nyack	New York
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	INTEGRIS Cancer Institute of Oklahoma Integris South West Med Center	Oklahoma City	Oklahoma
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	UMASS Memorial Medical Center	Worcester	Massachusetts
United States	Yuma Regional Medical Center	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  China,  Czechia,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Norway,  Philippines,  Romania,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time from randomization until treatment failure	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	Randomization to until end of study (up to 39 months after randomization of last participant)
Secondary	Complete Response rate at each timepoint	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)
Secondary	Response rate at each timepoint	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)
Secondary	Best response rate across all timepoints	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)
Secondary	Time to first response/time to first complete response	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
Secondary	Duration of response	Time from achievement of response to treatment failure Stable response at 6 months	Randomization to until end of study (up to 39 months after randomization of last participant)
Secondary	Stable response 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	At 6 months
Secondary	Stable response 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	At 1 year
Secondary	Duration of complete response	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)
Secondary	Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm	Probability to be treatment failure-free (as defined for the primary efficacy endpoint)	up to week 24
Secondary	Percentage of participants with bleeding events according to World Health Organization (WHO)	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)
Secondary	Number of participants receiving rescue treatment	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)
Secondary	Percentage of participants receiving rescue treatment	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)
Secondary	Change from baseline in the frequency of CD19+ B-cell counts	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)
Secondary	Change from baseline in the absolute number of CD19+ B-cell counts	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)
Secondary	Change from baseline on T-score of the PROMIS SF v1.0 Fatigue 13a	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)
Secondary	Change from baseline in ITP PAQ domain scores of symptoms, fatigue, bother (uncomfortable), activity	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)
Secondary	Time to first occurence 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	Randomization to until end of study (up to 39 months after randomization of last participant)
Secondary	Change from baseline in immunoglobulins	Change from baseline in immunoglobulin levels	Randomization to until end of study (up to 39 months after randomization of last participant)
Secondary	PK parameters: AUClast	AUClast: Area under the curve from time zero to the last measurable concentration sampling time (tlast)	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)
Secondary	PK parameters: AUCtau	AUCtau: Area under the curve calculated to the end of a dosing interval (tau)	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)
Secondary	PK parameters: Cmax	Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration	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)
Secondary	PK parameters: Tmax	Time to reach maximum (peak) observed plasma, blood, serum or other body fluid drug concentration	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)
Secondary	PK parameters: Accumulation ratio Racc	Accumulation ratio calculated using AUC values obtained after the last and first dose	After last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)
Secondary	Incidence of anti-ianalumab antibodies in serum (ADA assay) over time	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab	up to week 33
Secondary	Titer of anti-ianalumab antibodies in serum (ADA assay) over time	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab	up to week 33