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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05648968

Collaborator

(none)

Enrollment

Location

Arms

73.5

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Warm Autoimmune Hemolytic Anemia (wAIHA)	Biological: Ianalumab Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 30, 2022

Anticipated Primary Completion Date :

Mar 5, 2026

Anticipated Study Completion Date :

Feb 13, 2029

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Binary variable indicating whether a patient achieves a durable response [Randomization to Week 25]
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

Secondary Outcome Measures

Duration of response (Key Secondary) [Randomization to end of study (up to 39 months after randomization of last patient)]
• 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
Time from randomization to start of durable response in each treatment group [Randomization to end of study (up to 39 months after randomization of last patient)]
Durable response is defined as in primary endpoint.
Time from randomization to start of first response in each treatment group [Randomization to end of study (up to 39 months after randomization of last patient)]
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.
Time from randomization to start of complete response in each treatment group [Randomization to end of study (up to 39 months after randomization of last patient)]
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.
Response rate [Randomization to end of study (up to 39 months after randomization of last patient)]
Assessment of quality of response in each treatment group.
Complete response rate [Randomization to end of study (up to 39 months after randomization of last patient)]
Assessment of complete response rate in each treatment group.
Hemoglobine Levels [Randomization to end of study (up to 39 months after randomization of last patient)]
Assessment of hemoglobin levels in each treatment group.
Number of participants who received rescue treatment (overall & by type of rescue treatment) [Randomization to end of study (up to 39 months after randomization of last patient)]
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.
Percentage of participants who received rescue treatment (overall & by type of rescue treatment) [Randomization to end of study (up to 39 months after randomization of last patient)]
This is to assess the need for rescue treatment in all treatment groups.
Change from baseline in the the frequency and absolute number of CD19+ B cell counts [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 in whole blood
Time to first occurrence of B cell recovery, defined as ≥80% of baseline or ≥50 cells/μL [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 in whole blood
Change from baseline in immunoglobulin levels [Randomization until month 30]
Change from baseline in immunoglobulin levels (change in titers of IgG, IgM, IgA)
Change from baseline in the 8 domain scores and in the summary scores (PCS, MCS) of SF-36 questionnaire [Randomization to end of study (up to 39 months after randomization of last patient)]
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.
Change from baseline in the total score of PROMIS Fatigue-13a questionnaire [Randomization to end of study (up to 39 months after randomization of last patient)]
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.
Ianalumab PK parameter - AUClast [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).]
AUClast: area under the curve from time zero to last measurable concentration sampling time (tlast).
Ianalumab PK parameter - AUCtau [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).]
AUCtau: the AUV calculated to the end of a dosing interval (tau).
Ianalumab PK parameter - Accumulation ratio Racc [After last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).]
Accumulation ratio calculated using AUC values obtained between last and first dose
Ianalumab PK parameter - Cmax [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).]
Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration
Ianalumab PK parameter - Tmax [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).]
Time to reach maximum (peak) plasma, blood, serum or other body fluid drug concentration
Immunogenicity of ianalumab [Randomization to end of study (up to 39 months after randomization of last patient)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 <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 other immunologic disease requiring immunosuppressant treatments that are not allowed in this study
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
Neutrophils: <1000/mm3
Serum creatinine >1.5 × upper limit of normal (ULN) for adults or estimated glomerular filtration rate (eGFR)≤60 mL/min for adolescent
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)
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