A Study of Efficacy and Safety of Ianalumab in Previously Treated Patients With Warm Autoimmune Hemolytic Anemia
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 details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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
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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT05648968
Intervention or treatment
BIOLOGICAL: Ianalumab
DRUG: Placebo
Conditions
- Warm Autoimmune Hemolytic Anemia (wAIHA)
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Research sites nearby
Closest Location:
Novartis Investigative Site
Select from list below to view details:
Novartis Investigative Site
Garran, Australian Capital Territory, Australia
Novartis Investigative Site
Fitzroy, Victoria, Australia
Novartis Investigative Site
Melbourne, Victoria, Australia
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Who is running the clinical trial?
Novartis Pharmaceuticals
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Ianalumab low dose
| Biological: Ianalumab |
EXPERIMENTAL: Ianalumab high dose
| Biological: Ianalumab |
PLACEBO_COMPARATOR: Placebo
| Drug: Placebo |
What is the study measuring?
Primary Outcome
| 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
| 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) |
| 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) |
| 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) |
References
Clinical Trials Gov: A Study of Efficacy and Safety of Ianalumab in Previously Treated Patients With Warm Autoimmune Hemolytic AnemiaOther trials to consider
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