Study on the safety, efficacy, and tolerability of Secukinumab versus placebo in combination with standard therapy in patients with active lupus nephritis

Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, France, Germany, Greece, Guatemala, India, Italy, Japan, Korea, Republic of, Latvia, Mauritius, Mexico, Norway, Peru, Philippines, Portugal, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam (ICTRP)

ICTRP Studien-ID
NCT04181762 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
nicht verfügbar

Wissenschaftlicher Titel
A Two-year, Phase III Randomized, Double-blind, Parallel-group, Placebo-controlled Trial to Evaluate the Safety, Efficacy, and Tolerability of 300 mg s.c. Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis (ICTRP)

Öffentlicher Titel
Study of Safety, Efficacy and Tolerability of Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis (ICTRP)

Untersuchte Krankheit(en)
Lupus Nephritis (ICTRP)

Untersuchte Intervention
Drug: secukinumabDrug: Placebo (ICTRP)

Studientyp
Interventional (ICTRP)

Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)

Ein-/Ausschlusskriterien
Key inclusion criteria:

1. Adult male and female subjects aged 18 - 75 years old at the time of Baseline.

2. Confirmed diagnosis of:

- SLE with documented history of at least 4 of the 11 criteria for SLE as defined
by the American College of Rheumatology (ACR) (Tan et al 1982) revised by
(Hochberg 1997). [NOTE: The 4 criteria did not have to be present at the time
of Screening], OR

- LN as the sole clinical criterion in the presence of ANA or anti-dsDNA
antibodies.

3. Active lupus nephritis, as defined by meeting the 4 following criteria:

- Biopsy within 6 months prior to Screening visit indicating active
glomerulonephritis WHO or ISN/RPS Class III or IV LN [excluding III (C), IV-S
(C) and IV-G (C)] patients are permitted to have co-existing Class V. If no
biopsy was performed within 6 months of screening, a biopsy was to be performed
during the Screening period

- UPCR = 1 mg/mg at Screening.

- eGFR > 30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI).

- Active urinary sediment (presence of cellular casts (RBC or WBC casts)) or
hematuria (> 5 RBC per high power field or above the laboratory reference
range).

4. Subjects must have currently been on MPA, or willing to initiate SoC induction
therapy for LN according to the institutional practices using MPA or low-dose CYC in
addition to corticosteroids. For guidance, see published guidelines such as by
(Bertsias et al 2012, Hahn et al 2012).

5. Subjects must had been treated with anti-malarials (e.g. hydroxychloroquine), unless
contra-indicated, and the dose had been stable for at least 10 days prior to
Randomization.

6. Able to provide signed informed consent.

Key Exclusion criteria:

1. Severe renal impairment as defined by i.) Stage 4 CKD, or ii.) presence of oliguria
(defined as a documented urine volume < 400 mL/24 h), or iii.) ESRD required
dialysis or transplantation.

2. Known intolerance/hypersensitivity to MPA, or oral corticosteroids, or any component
of the study drug(s).

3. Subjects received any other biologic immunomodulatory therapy within 6 months prior
to Screening, excluding belimumab where 3 months were acceptable.

4. Previous exposure to secukinumab (AIN457) or any other biologic drug targeting IL-17
or the IL-17 receptor.

5. Subjects received any investigational drug within 1 month or five times the
half-life of enrollment, whichever was longer.

6. Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within
the 12 weeks prior to Baseline.

7. Treatment with a systemic calcineurin inhibitor (e.g. cyclosporine, tacrolimus)
within 12 weeks prior to Baseline

8. CYC use (i.v. or oral) within the month prior to Baseline.

9. Subjects requiring dialysis within the previous 12 months before Screening.

10. History of renal transplant.

11. Any severe progressive or uncontrolled concurrent medical condition, including
recent severe thromboembolic events, that, in the opinion of the principal
investigator, renders the subject unsuitable for the trial.

12. Active ongoing inflammatory diseases that might confound the evaluation of the
benefit of secukinumab therapy, including inflammatory bowel disease.

13. Presence of investigator-identified significant medical problems which at the
investigator's discretion would prevent the subject from participating in the study,
included but not limited to the following: myocarditis, pericarditis, poorly
controlled seizure disorder, acute confusional state, depression, severe
manifestations of neuropsychiatric SLE (NPSLE).

14. Chest X-ray, computerized tomography (CT) scan, or MRI with evidence of ongoing
infectious or malignant process, obtained within 3 months preceding the Screening
visit and evaluated by a qualified physician.

15. History of chronic, recurrent systemic infections, active tuberculosis infection, or
active systemic infections during the last two weeks (exception: common cold) prior
to Randomization.

16. Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
at Screening or Randomization.

17. History of lymphoproliferative disease or any known malignancy or history of
malignancy of any organ system treated or untreated within the past 5 years,
regardless of whether there was evidence of local recurrence or metastases (except
for skin Bowen's disease or basal cell carcinoma or actinic keratoses that had been
treated with no evidence of recurrence in the past 12 weeks, carcinoma in situ of
the cervix or non-invasive malignant colon polyps that had been removed).

18. Any of the following abnormal laboratory values on Screening evaluations as reported
by Central Laboratory:

- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or amylase >
2.5xULN

- Hemoglobin < 8g/dL

- Neutrophils < 1.0 x 109/L

- Platelet count < 50 x 109/L

21. Pregnant or lactating women. 22. Women of childbearing potential, defined as all
women physiologically capable of becoming pregnant, unless they were using highly
effective methods of contraception during the entire study or longer if required by
locally approved prescribing information (e.g., in European Union (EU) 20 weeks). Of
note: the highly effective methods of contraception were mandated due to SoC
medications used as per protocol (MPA and CYC).

In case local regulations deviated from the contraception methods listed above, local
regulations applied and were described in the informed consent form (ICF).

If stricter female or male contraception requirements were specified in the
country-specific label for induction and maintenance standard of care medications, they
had to be followed.

Note: Women were considered post-menopausal and not of childbearing potential if they had
12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g.,
age appropriate, history of vasomotor symptoms) or had surgical bilateral oophorectomy
(with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks
prior to enrollment. In the case of oophorectomy alone, only when the reproductive status
of the woman had been confirmed by follow-up hormone level assessment was she considered
not of childbearing potential. (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52 (ICTRP)

Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR);Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52;Average Daily Dose of Oral Corticosteroids;Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24;Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52;Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52;Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52;Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52;Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52;Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52;Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs);Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group;Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group (ICTRP)

Registrierungsdatum
27.11.2019 (ICTRP)

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Novartis Pharmaceuticals, Novartis Pharmaceuticals (ICTRP)

Sekundäre IDs
2019-003211-57, PACTR202211748997845, CAIN457Q12301 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04181762 (ICTRP)