A study of efficacy and safety of ianalumab in previously treated patients with warm autoimmune haemolytic anaemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

9 May 2023 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-510635-21-00

EudraCT number

2022-001773-31

ClinicalTrials.gov

NCT05648968

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Safety, Others, Efficacy, Pharmacokinetic

To demonstrate that either dose of ianalumab induces durable hemoglobin (Hb) response compared to placebo in patients with wAIHA. The primary clinical question of interest is: What is the effect of either dose of ianalumab versus placebo (with or without supportive care), in inducing durable hemoglobin response, in wAIHA patients ≥18 years of age who failed at least one line of treatment, regardless of premature discontinuation from study treatment or temporary treatment interruption/delay, and in the absence of rescue or prohibited treatment?

Secondary objectives 9

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
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.
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 and immunoglobulin levels at each treatment group
8. To assess the immunogenicity against ianalumab
9. To assess the quality of life (QoL) in each treatment group

Conditions and MedDRA coding

warm autoimmune haemolytic anaemia (wAIHA)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Written informed consent form (ICF) must be obtained prior to any screening assessments
2. Male or female participants aged 18 years and older on the day of signing the ICF
3. Participants with primary or secondary wAIHA (previously documented by 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 corticosteroid resistance, dependence, or intolerance
4. Hemoglobin concentration ≥5 g/dL and <10 g/dL and presence of symptoms related to anemia at Screening and Week 1.
5. The dose of supportive care must be stable for at least 4 weeks prior randomization.

Exclusion criteria 5

1. Patients with wAIHA secondary to hematologic disease involving bone marrow (e.g., chronic lymphocytic leukemia (CLL)) or another disease requiring prohibited medication. Of note, the patients with autoimmune diseases like lupus nephritis (LN), systemic lupus erythematosus (SLE), Primary Sjögren’s Syndrome (pSS) or autoimmune hepatitis (AIH) after wash-out from the treatments are allowed
2. Prior use of B-cell depleting therapy: • within 12 weeks prior randomization, or • no hematologic response to the last course of B-cell depleting therapy, irrespective of time of administration
3. Active viral, bacterial, or other infections (including active or latent tuberculosis or SARSCoV- 2) requiring systemic treatment at the time of screening or history of recurrent clinically significant infection
4. Known history of primary or secondary immunodeficiency, or patients that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B surface Antigen (HBsAg)/ Hepatitis B core antibody (HBcAb)-positive. Refer to Section 5.2 exclusion criterion #7b for exemptions applicable for patients who are HBsAg negative and HBcAb positive.
5. Live or live-attenuated vaccination within 4 weeks before randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 12

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 proportion of participants that receive rescue treatment overall and by type of rescue treatment
5. Time-standardized numbers of each type of rescue treatment
6. Change from baseline in time-standardized number of transfusions
7. Frequency of AEs and other safety parameters
8. Ianalumab concentration in serum and PK parameters after the first and last dose
9. B-cell levels: • 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
10. Immunoglobulins: • Change from baseline in immunoglobulin levels
11. Incidence and titer of anti-drug antibodies (ADA) in serum over time
12. Change from baseline in dedicated Patient Reported Outcomes (PROs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 15

Locations

6 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 79 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications