Warm Autoimmune Hemolytic Anemia (wAIHA)Phase 3VAYHIANCT05648968
A Study of Efficacy and Safety of Ianalumab in Previously Treated Patients With Warm Autoimmune Hemolytic Anemia
A Phase 3 study testing Ianalumab in people with Warm Autoimmune Hemolytic Anemia (wAIHA), run by Novartis Pharmaceuticals at 53 sites in 16 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Warm Autoimmune Hemolytic Anemia (wAIHA)
- What is being tested?
- Ianalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 53 sitesin 16 countries
- Study dates
- 30 Dec 2022to 19 Dec 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
53 sites in 16 countries.
53 sites in 16 countries
Japan8 sites
Novartis Investigative Site
Gifu, Gifu, 5011194
Novartis Investigative Site
Isehara, Kanagawa, 2591193
Novartis Investigative Site
Itabashi-ku, Tokyo, 1738610
Novartis Investigative Site
Kobe, Hyōgo, 6500047
Novartis Investigative Site
Matsuyama, Ehime, 7900024
Novartis Investigative Site
Narita, Chiba, 2868523
Novartis Investigative Site
Shinjuku Ku, Tokyo, 1600023
Novartis Investigative Site
Suita, Osaka, 5650871
China5 sites
Novartis Investigative Site
Dalian, 116000
Novartis Investigative Site
Guangzhou, Guangdong, 510515
Novartis Investigative Site
Hangzhou, Zhejiang, 310003
Novartis Investigative Site
Tianjin, 300020
Novartis Investigative Site
Tianjin, 300052
France4 sites
Novartis Investigative Site
Créteil, 94010
Novartis Investigative Site
Lille, 59037
Novartis Investigative Site
Nantes, 44093
Novartis Investigative Site
Nice, 06202
Germany4 sites
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Giessen, 35392
Novartis Investigative Site
Hanover, 30161
India4 sites
Novartis Investigative Site
Hyderabad, Telangana, 500082
Novartis Investigative Site
Lucknow, Uttar Pradesh, 226014
Novartis Investigative Site
Madurai, Tamil Nadu, 625107
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110029
Italy4 sites
Novartis Investigative Site
Bassano del Grappa, VI, 36061
Novartis Investigative Site
Milan, MI, 20100
Novartis Investigative Site
Milan, MI, 20122
Novartis Investigative Site
Novara, 28100
United States3 sites
Michigan Center of Medical Research
Farmington Hills, Michigan, 48334
University of Minnesota Med Center
Minneapolis, Minnesota, 55455
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Argentina3 sites
Novartis Investigative Site
Buenos Aires, C1039AAC
Novartis Investigative Site
Caba, C1015ABO
Novartis Investigative Site
CABA, Buenos Aires, C1414DRK
Malaysia3 sites
Novartis Investigative Site
George Town, Pulau Pinang, 10450
Novartis Investigative Site
Johor Bahru, 80100
Novartis Investigative Site
Kuching, Sarawak, 93586
Thailand3 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10700
Novartis Investigative Site
Chiang Mai, 50200
United Kingdom3 sites
Novartis Investigative Site
Birmingham, West Midlands, B15 2TH
Novartis Investigative Site
Leeds, LS1 3EX
Novartis Investigative Site
London, W12 0HS
Australia2 sites
Novartis Investigative Site
Garran, Australian Capital Territory, 2605
Novartis Investigative Site
Melbourne, Victoria, 3004
Israel2 sites
Novartis Investigative Site
Kfar Saba, 4428164
Novartis Investigative Site
Petah Tikva, 4941492
Singapore2 sites
Novartis Investigative Site
Singapore, 119074
Novartis Investigative Site
Singapore, 308433
Spain2 sites
Novartis Investigative Site
Barcelona, 08035
Novartis Investigative Site
Murcia, 30008
About this study
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
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.
Read the 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.
- Conditions
- Warm Autoimmune Hemolytic Anemia (wAIHA)
- Being tested
- Ianalumab, Placebo
- Keywords
- warm autoimmune hemolytic anemia, wAIHA, ianalumab, VAY736, B-cell depletion, B-cell Activating Factor Receptor (BAFF-R) blockade
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IanalumabBiological
Also called VAY736
i.v. infusion, prepared from concentrate solution
PlaceboDrug
i.v. infusion, prepared from matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Ianalumab low dose | Experimental | Participants will receive low dose ianalumab intravenously Receives: Biological: Ianalumab |
| Ianalumab high dose | Experimental | Participants will receive high dose ianalumab intravenously Receives: Biological: Ianalumab |
| Placebo | Placebo comparator | Participants will receive placebo intravenously Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Randomization to Week 25
Secondary outcomes (20)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Randomization to end of study (up to 39 months after randomization of last patient)
Hemoglobine Levels
Assessment of hemoglobin levels in each treatment group.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: Randomization to end of study (up to 39 months after randomization of last patient)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2022
- Study start30 Dec 2022
- Primary completion20 Feb 2026
- Study completion19 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Warm Autoimmune Hemolytic Anemia (wAIHA)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05648968
- Sponsor's protocol ID
- CVAY736O12301
- Other IDs
- 2022-001773-31, 2024-510635-21-00
- Acronym
- VAYHIA
- Status last verified
- Sep 2026
- First submitted
- 23 Nov 2022
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
- Expanded access
- Available