A Study of Efficacy and Safety of Ianalumab in Previously Treated Patients With Warm Autoimmune Hemolytic Anemia

Warm Autoimmune Hemolytic Anemia (wAIHA) Clinical Trial

— VAYHIA  

Official title:

A Phase 3, Randomized, Double-blind, Study to Assess Efficacy and Safety of Ianalumab (VAY736) Versus Placebo in Warm Autoimmune Hemolytic Anemia (wAIHA) Patients Who Failed at Least One Line of Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05648968
• Other study ID #: CVAY736O12301
• Secondary ID: 2022-001773-31
• Status: Recruiting
• Phase: Phase 3
• Start date: December 30, 2022
• Est. completion date: February 8, 2029

Study information

• Verified date: March 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 efficacy and safety of ianalumab compared to placebo in patients with warm autoimmune hemolytic anemia, who failed at least one line of treatment.

Description:

The primary objective is to demonstrate that either dose of ianalumab induces a durable hemoglobin response compared to placebo in patients with wAIHA.

The key secondary objective is to demonstrate that either dose of ianalumab maintains a durable hemoglobin response that is sustained beyond end of the treatment period, compared to placebo.

Participants are randomized to two different doses of ianalumab or placebo. Participants who were assigned to placebo arm and not responding to treatment may be treated with open label ianalumab using the higher dose.

The investigational treatment will be supplied in a double-blinded manner. For the open label period, ianalumab will be provided in an open label manner.

In addition to the randomized treatment (ianalumab or placebo), specific supportive care medication as defined in the protocol is allowed. If clinically indicated (e.g., to ensure patient safety), the treating physician may also administer rescue medication.

The study consists of the treatment period, efficacy and safety follow-up periods. The visit frequency will be every other week during the treatment and primary endpoint follow up period; for safety monitoring monthly during the first 20 weeks after last dose and afterwards quarterly up to 2 years from the last dose. For participants in durable response, additional visits for efficacy will occur monthly during the first 2 years after the last dose, and afterwards quarterly until loss of response or end of study, latest until up to 39 months post randomization of the last participant.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: February 8, 2029
• Est. primary completion date: March 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 18 years and older at time of signing consent

• Patients with primary or secondary wAIHA documented by positive direct antiglobulin test specific for anti-IgG or anti-IgA, who had an insufficient response to, or relapsed after at least one line of treatment, including patients with steroid resistance, dependence or intolerance

• Hemoglobin concentration at screening and at Week 1 >=5 g/dL and <10 g/dL, associated with presence of symptoms related to anemia

• The dose of supportive care must be stable for at least 4 weeks prior to randomization into the study

Key Exclusion Criteria:

• wAIHA secondary to hematologic disease involving bone marrow (e.g., CLL) or another immunologic disease requiring prohibited medication as per protocol. Patients with autoimmune diseases after wash-out from the treatments are allowed.

• Presence of other forms of AIHA (cold or intermediate forms), Evans Syndrome or other cytopenias

• Prior use of B-cell depleting therapy (e.g., rituximab) within 12 weeks prior to randomization, or without hematological response to the last course of B-cell depleting therapy

• Neutrophils: <1000/mm3

• Serum creatinine >1.5 × upper limit of normal (ULN)

• Immunoglobulin G (IgG) <5g/L

• Active viral, bacterial or other infections (including tuberculosis and SARS-CoV-2) requiring systemic treatment at time of screening, or history of recurrent clinically significant infection

• Positivity for hepatitis C virus, hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb). HBcAb positive patients can be enrolled if HBsAg negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given.

• Known history of primary or secondary immunodeficiency, or a positive human immune deficiency virus (HIV) test result

• Live or live-attenuated vaccination within 4 weeks before randomization

• History of splenectomy

Other protocol-defined Inclusion/Exclusion may apply.

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Hemolysis
• Warm Autoimmune Hemolytic Anemia (wAIHA)

Intervention

Biological:
• Ianalumab
i.v. infusion, prepared from concentrate solution

Drug:
• Placebo
i.v. infusion, prepared from matching placebo

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Australia	Novartis Investigative Site	Canberra	Australian Capital Territory
Australia	Novartis Investigative Site	Prahran	Victoria
China	Novartis Investigative Site	Dalian
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Kunming	Yunnan
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Wuhan	Hubei
France	Novartis Investigative Site	Blois Cedex
France	Novartis Investigative Site	Caen	Cedex
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Le Mans	Cedex 09
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Vandoeuvre Les Nancy
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Giessen
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Hannover
Hungary	Novartis Investigative Site	Debrecen
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	Madurai	Tamil NADU
India	Novartis Investigative Site	New Delhi
Israel	Novartis Investigative Site	Afula
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Zerifin	HaMerkaz
Italy	Novartis Investigative Site	Avellino	AV
Italy	Novartis Investigative Site	Bari	BA
Italy	Novartis Investigative Site	Bassano Del Grappa	VI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Novara
Japan	Novartis Investigative Site	Aomori
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Gifu-city	Gifu
Japan	Novartis Investigative Site	Isehara	Kanagawa
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kobe-city	Hyogo
Japan	Novartis Investigative Site	Matsuyama-city	Ehime
Japan	Novartis Investigative Site	Narita	Chiba
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Suita	Osaka
Japan	Novartis Investigative Site	Yamagata
Malaysia	Novartis Investigative Site	Johor Bahru
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
Romania	Novartis Investigative Site	Bucuresti
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Murcia
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United States	Montefiore Medical Center .	Bronx	New York
United States	Gabrail Cancer Center	Canton	Ohio
United States	STAT Research Inc Premier Clin Res LLC STAT Res	Dayton	Ohio
United States	Napa Research	Margate	Florida
United States	University of Minnesota Med Center	Minneapolis	Minnesota
United States	Inspira Medical Cent Mullica Hill	Mullica Hill	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  China,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Japan,  Malaysia,  Romania,  Singapore,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Binary variable indicating whether a patient achieves a durable response	Durable response: hemoglobin level =10 g/dL and =2 g/dL increase from baseline, for a period of at least eight consecutive weeks between W9 and W25, in the absence of rescue medication or prohibited treatment	Randomization to Week 25
Secondary	Duration of response (Key Secondary)	• For patients who previously reached durable response: Time from first hemoglobin assessment showing durable response to confirmed loss of durable response, defined as the first of the following events: hemoglobin level <10 g/dL in at least two consecutive weekly assessments,; start of any rescue medication or prohibited treatment,; death; • For patients who did not achieve the durable response according to primary endpoint definition: duration will be 0 days	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Time from randomization to start of durable response in each treatment group	Durable response is defined as in primary endpoint.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Time from randomization to start of first response in each treatment group	Response is defined as hemoglobin level of at least 10 g/dL and an increase of at least 2 g/dl from baseline, or normalization of hemoglobin (at least 11 g/dL for women and 12 g/dL for men), without biochemical resolution of hemolysis.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Time from randomization to start of complete response in each treatment group	Complete response is defined as normalization of hemoglobin levels and no evidence of hemolysis (normal levels of indirect bilirubin, LDH, haptoglobin and reticulocytes), in the absence of red blood cell transfusions.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Response rate	Assessment of quality of response in each treatment group.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Complete response rate	Assessment of complete response rate in each treatment group.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Hemoglobine Levels	Assessment of hemoglobin levels in each treatment group.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Number of participants who received rescue treatment (overall & by type of rescue treatment)	This is to assess the need for rescue treatment in all treatment groups, measured as time-standardized numbers of each type of rescue treatment and as change from baseline in time-standardized number of transfusions.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Percentage of participants who received rescue treatment (overall & by type of rescue treatment)	This is to assess the need for rescue treatment in all treatment groups.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Change from baseline in the the frequency and absolute number of CD19+ B cell counts	Change from baseline in the the frequency and absolute number of CD19+ B cell counts in whole blood	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Time to first occurrence of B cell recovery, defined as =80% of baseline or =50 cells/µL	Time to first occurrence of B cell recovery, defined as =80% of baseline or =50 cells/µL in whole blood	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Change from baseline in immunoglobulin levels	Change from baseline in immunoglobulin levels (change in titers of IgG, IgM, IgA)	Randomization until month 30
Secondary	Change from baseline in the 8 domain scores and in the summary scores (PCS, MCS) of SF-36 questionnaire	SF-36 v2.0 (acute) includes 36 items that assess general health related quality of life covering 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role-emotional health and mental health.; Scores for the 8 domains are generated, as well as a physical component summary (PCS) score and a mental component summary (MCS) score.; Responses to items are based on a 5-point Likert scale. Scores below 50 indicate less than average health, while scores above 50 indicate better than average health.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Change from baseline in the T-score of PROMIS Fatigue-13a questionnaire	Assessment of quality of life in each treatment group. The PROMIS Short Form v1.0 Fatigue-13a includes 13 items that assess fatigue. All items in the PROMIS-Fatigue-13a utilize a 5-point response scale (e.g., not at all, a little bit, somewhat, quite a bit, very much).; Higher scores on the PROMIS-Fatigue-13a represent greater fatigue.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Ianalumab PK parameter - AUClast	AUClast: area under the curve from time zero to last measurable concentration sampling time (tlast).	After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
Secondary	Ianalumab PK parameter - AUCtau	AUCtau: the AUV calculated to the end of a dosing interval (tau).	After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
Secondary	Ianalumab PK parameter - Accumulation ratio Racc	Accumulation ratio calculated using AUC values obtained between last and first dose	After last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
Secondary	Ianalumab PK parameter - Cmax	Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration	After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
Secondary	Ianalumab PK parameter - Tmax	Time to reach maximum (peak) plasma, blood, serum or other body fluid drug concentration	After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
Secondary	Immunogenicity of ianalumab	Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time. Confirmed anti-drug-antibody positive samples will be further characterized for neutralizing capacity.	Randomization to end of study (up to 39 months after randomization of last patient)