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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Warm Autoimmune Hemolytic Anemia (wAIHA)
• Intervention / Treatment: Biological: Ianalumab; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • Buenos aires, Argentina, C1039AAC
    • Recruiting
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1414DRK
      • Recruiting
      • Novartis Investigative Site
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1015ABO
      • Recruiting
      • Novartis Investigative Site
• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2605
      • Recruiting
      • Novartis Investigative Site
  • Victoria
    • Prahran, Victoria, Australia, 3181
      • Recruiting
      • Novartis Investigative Site
• China
  • Dalian, China, 116000
    • Recruiting
    • Novartis Investigative Site
  • Tianjin, China, 300052
    • Recruiting
    • Novartis Investigative Site
  • Tianjin, China, 300020
    • Recruiting
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Novartis Investigative Site
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • Novartis Investigative Site
  • Yunnan
    • Kunming, Yunnan, China, 650101
      • Recruiting
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • Novartis Investigative Site
• France
  • Blois Cedex, France, 41000
    • Recruiting
    • Novartis Investigative Site
  • Creteil, France, 94010
    • Recruiting
    • Novartis Investigative Site
  • Lille Cedex, France, 59 037
    • Recruiting
    • Novartis Investigative Site
  • Nantes Cedex 1, France, 44093
    • Recruiting
    • Novartis Investigative Site
  • Nice, France, 06202
    • Recruiting
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Recruiting
    • Novartis Investigative Site
  • Vandoeuvre Les Nancy, France, 54511
    • Recruiting
    • Novartis Investigative Site
  • Cedex
    • Caen, Cedex, France, 14033
      • Recruiting
      • Novartis Investigative Site
  • Cedex 09
    • Le Mans, Cedex 09, France, 72037
      • Recruiting
      • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Recruiting
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Recruiting
    • Novartis Investigative Site
  • Giessen, Germany, 35392
    • Recruiting
    • Novartis Investigative Site
  • Greifswald, Germany, 17475
    • Recruiting
    • Novartis Investigative Site
  • Hannover, Germany, 30161
    • Recruiting
    • Novartis Investigative Site
• Hungary
  • Debrecen, Hungary, 4032
    • Recruiting
    • Novartis Investigative Site
• India
  • New Delhi, India, 110029
    • Recruiting
    • Novartis Investigative Site
  • Tamil NADU
    • Madurai, Tamil NADU, India, 625107
      • Recruiting
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Recruiting
      • Novartis Investigative Site
• Israel
  • Afula, Israel, 1834111
    • Recruiting
    • Novartis Investigative Site
  • Kfar Saba, Israel, 44281
    • Recruiting
    • Novartis Investigative Site
  • Petach Tikva, Israel, 4941492
    • Recruiting
    • Novartis Investigative Site
  • HaMerkaz
    • Zerifin, HaMerkaz, Israel, 7030000
      • Recruiting
      • Novartis Investigative Site
• Italy
  • Novara, Italy, 28100
    • Recruiting
    • Novartis Investigative Site
  • AV
    • Avellino, AV, Italy, 83100
      • Recruiting
      • Novartis Investigative Site
  • BA
    • Bari, BA, Italy, 70124
      • Recruiting
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20122
      • Recruiting
      • Novartis Investigative Site
    • Milano, MI, Italy, 20157
      • Recruiting
      • Novartis Investigative Site
  • VI
    • Bassano Del Grappa, VI, Italy, 36061
      • Recruiting
      • Novartis Investigative Site
• Japan
  • Aomori, Japan, 030 8553
    • Recruiting
    • Novartis Investigative Site
  • Yamagata, Japan, 990 9585
    • Recruiting
    • Novartis Investigative Site
  • Chiba
    • Narita, Chiba, Japan, 286-8523
      • Recruiting
      • Novartis Investigative Site
  • Ehime
    • Matsuyama-city, Ehime, Japan, 790-0024
      • Recruiting
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Recruiting
      • Novartis Investigative Site
  • Gifu
    • Gifu-city, Gifu, Japan, 501-1194
      • Recruiting
      • Novartis Investigative Site
  • Hyogo
    • Kobe-city, Hyogo, Japan, 650-0047
      • Recruiting
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Recruiting
      • Novartis Investigative Site
  • Osaka
    • Suita, Osaka, Japan, 565 0871
      • Recruiting
      • Novartis Investigative Site
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Recruiting
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Recruiting
      • Novartis Investigative Site
• Malaysia
  • Johor Bahru, Malaysia, 80100
    • Recruiting
    • Novartis Investigative Site
  • Penang, Malaysia, 10050
    • Recruiting
    • Novartis Investigative Site
  • Pulau Pinang, Malaysia, 10990
    • Recruiting
    • Novartis Investigative Site
  • Selangor, Malaysia, 68000
    • Recruiting
    • Novartis Investigative Site
  • MYS
    • Kuala Lumpur, MYS, Malaysia, 56000
      • Recruiting
      • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Novartis Investigative Site
• Romania
  • Bucuresti, Romania, 013975
    • Recruiting
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119228
    • Recruiting
    • Novartis Investigative Site
  • Singapore, Singapore, S308433
    • Recruiting
    • Novartis Investigative Site
• Spain
  • Murcia, Spain, 30008
    • Recruiting
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Recruiting
      • Novartis Investigative Site
• Taiwan
  • Taoyuan, Taiwan, 33305
    • Recruiting
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Recruiting
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Recruiting
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Recruiting
    • Novartis Investigative Site
• United Kingdom
  • Leeds, United Kingdom, LS1 3EX
    • Recruiting
    • Novartis Investigative Site
  • London, United Kingdom, E1 1BB
    • Recruiting
    • Novartis Investigative Site
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Novartis Investigative Site
• United States
  • Florida
    • Margate, Florida, United States, 33063
      • Recruiting
      • Napa Research
      • Principal Investigator: Emilio Araujo-Mino
      • Contact: Maria Marin; Email: Maria@napa-trials.com
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota Med Center
      • Contact: Diondra Howard; Email: howar709@umn.edu
      • Principal Investigator: Marshall Mazepa
  • New Jersey
    • Mullica Hill, New Jersey, United States, 08062
      • Recruiting
      • Inspira Medical Cent Mullica Hill
      • Principal Investigator: Erev Tubb
      • Contact: Jennifer Hart; Phone Number: 856-641-7526; Email: KartJ@ihn.org
  • New York
    • Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center .
      • Principal Investigator: Irina Murakhovskaya
      • Contact: Noelle Townsend; Phone Number: 718-920-2680; Email: noelle.townsend@einsteinmed.edu
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer Center
      • Contact: Phone Number: 330-492-3345
      • Principal Investigator: Nashat Y Gabrail
    • Dayton, Ohio, United States, 45402
      • Recruiting
      • STAT Research Inc Premier Clin Res LLC STAT Res
      • Principal Investigator: Charles Bane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ianalumab low dose; Participants will receive low dose ianalumab intravenously	Biological: Ianalumab; i.v. infusion, prepared from concentrate solution; Other Names: VAY736
Experimental: Ianalumab high dose; Participants will receive high dose ianalumab intravenously	Biological: Ianalumab; i.v. infusion, prepared from concentrate solution; Other Names: VAY736
Placebo Comparator: Placebo; Participants will receive placebo intravenously	Drug: Placebo; i.v. infusion, prepared from matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
Hemoglobine Levels	Assessment of hemoglobin levels in each treatment group.	Randomization to end of study (up to 39 months after randomization of last patient)
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)
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)
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)
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)
Change from baseline in immunoglobulin levels	Change from baseline in immunoglobulin levels (change in titers of IgG, IgM, IgA)	Randomization until month 30
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)
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).
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).
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).
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).
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).
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)
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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2022
• Primary Completion (Estimated): March 2, 2026
• Study Completion (Estimated): February 8, 2029

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 13, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: VAY736; B-cell depletion; wAIHA; ianalumab; warm autoimmune hemolytic anemia; B-cell Activating Factor Receptor (BAFF-R) blockade
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: CVAY736O12301; 2022-001773-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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 expert 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 is available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No