warm autoimmune haemolytic anaemia (wAIHA) MedDRA version: 25.0 Level: LLT Classification code 10047822 Term: Warm type haemolytic anaemia System Organ Class: 100000004851
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 18 years and older at time of signing consent - Patients with primary or secondary wAIHA, as previously documented by a positive direct antiglobulin test (DAT) 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 - Haemoglobin concentration at screening =65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: -wAIHA secondary to haematologic 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 randomisation -Neutrophils: 1.5 x upper limit of normal (ULN) - Active viral, bacterial or other infections (including tuberculosis -TB or SARS-CoV-2) requiring systemic treatment at the time of screening, or history of recurrent clinically significant infections (e.g. bacterial infections with encapsulated organisms) - 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 of randomisation - History of splenectomy Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that either dose of ianalumab induces durable hemoglobin response compared to placebo, in patients with wAIHA who failed at least one previous line of treatment;Secondary Objective: Key secondary objective: 1- To demonstrate that either dose of ianalumab maintains durable hemoglobin response, that is sustained beyond the end of the treatment period, compared to placebo Other secondary objectives: 2- To assess the time to durable response / response / complete response in each treatment group 3- To assess the quality of response in each treatment group (response, complete response, hemoglobin levels). 4- To assess the need for rescue treatments in each treatment group 5- To assess the safety profile of ianalumab 6- To characterize the pharmacokinetics (PK) of ianalumab 7- To assess B-cell levels at each treatment group 8- To assess immunoglobulin levels at each treatment group 9- To assess the immunogenicity of ianalumab 10- To assess the quality of life (QoL) in each treatment group;Primary end point(s): Binary variable indicating whether a patient achieves a durable response (Hb >=10 g/dL and> =2 g/dL increase from baseline), for a period of at least 8 weeks, between W9 and W25, in the absence of rescue or prohibited treatment;Timepoint(s) of evaluation of this end point: Randomisation until W25 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1- 5: Randomization to end of study (up to 39 months after randomization of last patient) 6i) After first dose of study treatment and after last dose 6ii) First dose until last dose of study treatment 6iii) After first dose of study treatment and after last dose 7: Randomization to end of study (up to 39 months after randomization of last patient) 8: Randomization to 2 years post last dose 9: First dose of study treatment (pre-dose) to 20 weeks post last dose 10: Randomization to end of study (up to 39 months after randomization of last patient);Secondary end point(s): 1- Duration of response 2- Time from randomization to achievement of durable response, to first response, to first complete response 3- Response rate, complete response rate and hemoglobin level 4- Number and percentage of participants who received rescue; treatment overall and by type of rescue medication; Time-standardized numbers of each type of rescue treatment; Change from baseline in time-standardized number of transfusions 5-frequency of adverse events and other safety parameters 6- Ianalumab PK parameters – (i) AUClast, AUCtau, (ii) accumulation ratio Racc, (iii) Cmax, Tmax 7- Change from baseline in the frequency and absolute number of CD19+B cell counts; Time to first occurrence of B Cell recovery, defined as >=80% of baseline or >=50 cells/µl 8- Change from baseline in immunoglobulin levels 9- Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time 10- Change from baseline in the 8 domain scores and in the summary scores (PCS, MCS) of SF-36 questionnaire; Change from baseline in the total score of PROMIS fatigue-13a questionnaire | — |
Countries
Argentina, Australia, China, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactTrial Monitoring Organization (TMo)
Novartis Farmacéutica, S.A.
Outcome results
None listed