Study of efficacy, safety and tolerability of ianalumab versus placebo, in combination with SoC therapy, in participants with active lupus nephritis

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] - Immune System Diseases [C20]

Trial duration

14 Jul 2022 → ongoing

Decision date (initial)

2024-07-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-508559-37-00

EudraCT number

2020-005830-14

ClinicalTrials.gov

NCT05126277

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To demonstrate superiority of ianalumab, compared to placebo, in proportion of participants in achieving stable complete renal response (CRR) at Week 72

Secondary objectives 10

1. To demonstrate superiority of ianalumab, compared to placebo, in time to first occurrence of XX from baseline up to Week 72
2. To demonstrate superiority of ianalumab, compared to placebo, in proportion of participants achieving stable complete renal response (CRR) at Week 72 while maintaining daily corticosteroid dose ≤5 mg/day between Week 24 and Week 72
3. To demonstrate superiority of ianalumab, compared to placebo, in proportion of participants experiencing renal-related event or death through Week 72
4. To demonstrate superiority of ianalumab, compared to placebo, in proportion of participants achieving stable overall renal response (ORR) at Week 48
5. To demonstrate superiority of ianalumab, compared to placebo in BILAG-2004 at Week 72
6. To demonstrate superiority of ianalumab, compared to placebo, in FACIT-Fatigue at Week 72
7. To demonstrate superiority of ianalumab XX, compared to placebo, in proportion of participants achieving stable CRR and the secondary objectives listed above
8. To evaluate immunogenicity of ianalumab
9. To characterize the pharmacokinetics (PK) of ianalumab
10. To evaluate immunogenicity of ianalumab

Conditions and MedDRA coding

Lupus nephritis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com. .

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Adult male and female participants aged 18 years or older at the time of screening
2. Weigh at least 35 kg at screening
3. Have a confirmed clinical diagnosis of SLE according to EULAR/ACR SLE classification criteria
4. Have a positive anti-nuclear antibody (ANA) test result defined as an ANA titer ≥1:80 (based on an indirect HEp-2 immunofluorescence assay or solid-phase ANA immunoassay with at least equivalent performance) at screening based on central laboratory results or a documented, positive historical result (ANA titer ≥1:80)
5. Presence of active LN at screening requiring induction therapy, as defined by meeting the 3 following criteria: • Renal biopsy within 6 months prior to screening period indicating ISN/RPS class III or IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous LN. If no biopsy was performed within 6 months prior to screening period, a biopsy will need to be performed during the screening period after having met all other inclusion/exclusion criteria. • UPCR ≥1.0 g/g on 24-hour urine collection at Screening • eGFR ≥25mL/min/1.73 m2
6. Newly diagnosed participants, as well as pre-treated LN participants (including refractory cases) can be included, as long as they are currently on, or willing to initiate SoC induction therapy for LN using MPA. • Induction therapy, as defined by treatment including both high dose corticosteroids and MPA, should be initiated prior to or on day of randomization. • Anti-malarial treatment at stable dosing prior to randomization is strongly recommended, in the absence of contraindications. • Participants on azathioprine treatment at Screening must be switched to MPA prior to randomization.
7. Receipt of at least one dose of pulse methylprednisolone i.v. (250-1000 mg per day up to 3000 mg cumulative dose) or equivalent for treatment of current episode of active LN within 60 days prior to randomization. Participants who cannot take the pulse i.v. corticosteroid therapy should directly start on 0.8-1.0 mg/kg/day (max 80 mg/day) oral predniso(lo)ne
8. Able to provide signed informed consent

Exclusion criteria 17

1. Severe renal impairment as defined by i) presence of oliguria (defined as a documented urine volume <400 mL/24 hrs), or ii) End-Stage Renal Disease (ESRD) requiring dialysis or transplantation
2. Prior treatment with any of the following • Within 12 weeks prior to randomization o belimumab, telitacicept, abatacept, TNF-α mAb, immunoglobulins (i.v./s.c.) plasmapheresis o any other immuno-suppressants (e.g., i.v. or oral cyclophosphamide, calcineurin inhibitors, JAK inhibitors or other kinase inhibitors) o thalidomide treatment and/or methotrexate • Imidazole derivative (e.g., azathioprine, mizoribine) must be discontinued prior to starting treatment with MPA
3. Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within 12 weeks prior to randomization
4. History of major organ transplant or hematopoietic stem cell/bone marrow transplant or are due to receive transplantation
5. Any one of the following laboratory values at screening: • Hemoglobin (Hgb) <8.0 g/dL (<5 mmol/L), or <7.0 g/dL (<4.3 mmol/L) if related to participant's SLE such as in active hemolytic anaemia • Platelet count <25 x 103/µL • Absolute neutrophil count (ANC) <0.8 x 103/µL
6. Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection or history of recurrent clinically significant infection which in the opinion of the investigator will place the participant at risk for participation.
7. Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). xxx
8. Evidence of active tuberculosis (TB) infection xxx.
9. Pregnant or nursing (lactating) women
10. United States (and other countries, if locally required): sexually active male participants who do not agree to use barrier protection during intercourse with women of child-bearing potential while taking study treatment. As condom use alone has a reported failure rate exceeding 1% per year, it is recommended female partners of male study participants use a second method of birth control.
11. History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component of the study drug(s) or its excipients or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug
12. Receipt of live/attenuated vaccine within a 4-week period prior to randomization
13. History of primary or secondary immunodeficiency, including a positive HIV test result
14. History of malignancy of any organ system (other than localized basal cell carcinoma or squamous cell carcinoma of the skin or
15. Any surgical, medical, psychiatric or additional physical condition that may jeopardize participation in this study
16. Sclerosis in >50% of glomeruli on renal biopsy
17. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline. Use of the following Traditional Chinese Medicines: Total glucoside of peony (TGP) or Tripterygium glycosides (TG) administered within 30 days prior to randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Achieving stable CRR at Week 72; participants who discontinue treatment before Week 72 or use corticosteroids at a dose >7.5 mg/day after Week 60 will be considered non-responders

Secondary endpoints 12

1. Time to first occurrence of XX from baseline up to Week 72
2. Achieving stable CRR at Week 72 while maintaining daily corticosteroid dose ≤5mg/day between Week 24 and Week 72. Participants who discontinue treatment before Week 72 will be considered non-responders
3. Experiencing renal flares related event or death through Week 72
4. Achieving of stable ORR at Week 48; participants who discontinue treatment before Week 48 or use corticosteroids at a dose >7.5 mg/day after Week 36 will be considered non-responders
5. Change from baseline in BILAG-2004 at Week 72
6. Change from baseline in FACIT-Fatigue at Week 72
7. Treatment-emergent Adverse Events (TEAEs)
8. Serious Adverse Events (SAEs)
9. Vital signs
10. Clinical laboratory measurements
11. Ianalumab concentration in serum and calculated PK parameters
12. Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time

Investigational products

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

Test 2

Placebo 1

Auxiliary 6

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 16

Locations

9 EU/EEA countries · 43 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 106 files

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

Application history

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