ANIFROLUMAB for Proliferative lupus nephritis

Inclusion criteria

• {"criterion_text":"- Age 18 through 70 years at the time of Screening.\n- Any negative PCR or antigen test result (central or local laboratory, as appropriate) as per local policies at Screening in addition to no known or suspected COVID 19 exposure within 2 weeks prior to Screening.\n- Body weight ≥ 40.0 kg.\n- Females who have been or are sexually-active with an intact cervix must have documentation of a cervical cancer screening (Pap smear or HPV tests as per local guidelines) with a normal test result within 2 years prior to randomization.\n- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (as described in protocol).\n- Fulfills updated 2019 SLE criteria.\n- Positive ANA, anti-dsDNA, or anti-Sm test result in sample obtained during Screening or historical.\n- Urine protein to creatinine ratio > 1 mg/mg (113.17 mg/mmol) (mean of 2 spot UPCR [FMV] samples obtained during Screening).\n- Active proliferative LN Class III or IV either with or without the presence of Class V (excluding pure Class III[C], IV-S[C], or IV-G[C]) according to the 2003 ISN/RPS classification based on a renal biopsy obtained within 6 months prior to signing the ICF or during Screening Period, and in the opinion of the investigator, participant needs high dose corticosteroids and immunosuppressive therapy.\n- eGFR ≥ 35 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula).\n- Adequate peripheral venous access.\n- Chest radiograph (obtained during Screening or within 12 weeks prior to signing of the informed consent) or a CT scan of the chest (within 12 weeks of signing the informed consent) that meets all of the following criteria: No evidence of current active infection (eg, pneumonia, TB) or previous TB; No evidence of malignancy; No evidence of pulmonary nodules suspicious for lung cancer that have not been appropriately followed-up prior to enrolment, No clinically significant abnormalities (unless due to SLE).\n- Meets all of the following TB criteria: No signs or symptoms of active TB prior to or during any Screening visit; No medical history or past physical examinations suggestive of active TB; A chest radiograph during the Screening Period or within 12 weeks prior to signing the ICF with no evidence of active or signs of prior TB infection; No recent contact with a person with active TB OR if there has been such contact, referral to a physician specializing in TB to undergo additional evaluation prior to Week 0 (Day 1) (documented comprehensively in source) and, if warranted, receipt of appropriate treatment for latent TB at or before the first administration of study intervention; No history of latent TB prior to signing the ICF, with the exception of latent TB with documented completion of appropriate treatment. The participant must undergo an IGRA (eg, QFT-G test) test for TB obtained from the study central laboratory at Screening with results in line with protocol specified rules."}

Exclusion criteria

• {"criterion_text":"- A diagnosis of pure Class V LN based on renal biopsy obtained within 6 months prior to signing the ICF or during Screening\n- Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years prior to the ICF\n- Clinically significant chronic infection within 8 weeks prior to signing the ICF (chronic nail infections are allowed) or any infection requiring hospitalization or treatment with IV anti-infectives not completed at least 4 weeks prior to the ICF\n- Any infection requiring oral anti-infectives (including antivirals) within 2 weeks prior to Week 0 (Day 1)\n- History of cancer, apart from: Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥3 months prior to Week 0 (Day 1); Cervical cancer in situ treated with apparent success with curative therapy ≥1 year prior to Week 0 (Day 1)\n- Any history of severe COVID-19 infection or any prior COVID-19 infection with documented long COVID and/or clinically significant unresolved sequelae. Any mild/asymptomatic COVID-19 infection within the last 6 weeks prior to first dosing\n- Failure to comply with all required Screening procedures due to circumstances related to pandemic or public health emergency\n- Prior receipt of anifrolumab\n- Previous receipt of >2 investigational treatments for LN since time of diagnosis of LN and through signing the ICF\n- Known intolerance to ≤1.0 g/day of MMF\n- Receipt of any commercially available biologic agent within 5 half-lives prior to signing of the ICF\n- History of dialysis within 12 months prior to the ICF or expected need for renal replacement therapy (dialysis or renal transplant) within a 6-month period\n- Receipt of any of the following prior to signing the ICF: Receipt of B cell-depleting therapy ≤26 weeks prior to signing the ICF or if therapy was administered >26 weeks ago, if absolute B cell count is <50 cells/microliter\n- A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy, human proteins, or monoclonal antibodies\n- \"Receipt of any of the following: -Any live or attenuated vaccine within 8 weeks prior to signing the ICF (killed vaccines are acceptable) -Any prohibited medication listed in Appendix O not discontinued according to the prescribed timeframe prior to signing of ICF -Blood transfusion or receipt of blood products, except human albumin, within 4 weeks prior to signing the ICF -Any of the following for current LN flare (ie, since the qualifying renal biopsy): IV cyclophosphamide >2 pulses of high-dose (≥0.5 g/m2) or >4 doses of low dose (500 mg every 2 weeks) or Average MMF >2.5 g/day (or >1800 mg/day of enteric coated mycophenolate sodium) for > 8 weeks or Tacrolimus >4 mg/day for more than 8 weeks or 4 weeks prior to signing the ICF; Cyclosporine for more than 8 weeks or during last 8 weeks prior to signing the ICF; Voclosporin for more than 8 weeks or during last 8 weeks prior to signing the ICF; Belimumab for more than 12 weeks or during last 12 weeks prior to signing the ICF\"\n- Receipt of any commercially available Janus kinase (JAK) inhibitor ≤12 weeks or Bruton’s tyrosine kinase (BTK) inhibitor ≤24 weeks prior to the ICF\n- Any new medicinal cannabinoid should not be started during the course of the study.\n- Participation in another clinical study with another intervention (besides anifrolumab) administered within 4 weeks prior to ICF signing or within 5 half-lives of the study intervention used in that study, whichever is longer\n- \"Within 4 weeks of Week 0 (Day 1),any of the following: -AST >2.5 × ULN -ALT >2.5 × ULN -TBL >ULN (unless due to Gilbert’s syndrome) -Glycosylated hemoglobin > 8% (or >0.08) at Screening (diabetic participants only) -Neutrophil count <1 × 10^3/μL (or <1.0 × 109/L) -Platelet count <25 × 10^3/μL (or <25 × 109/L) -Hemoglobin <8 g/dL (or <80 g/L)\"\n- History of, or current renal diseases (other than LN) that could interfere with the LN assessment and confound the disease activity assessment (eg, diabetic nephropathy)\n- \"History of recurrent infection requiring hospitalization and/or IV antibiotics (eg, 2 or more of the same type of infection over the previous 52 weeks)\"\n- Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for HIV confirmed by the central lab at Screening\n- Confirmed positive test for hepatitis B serology (HBsAB or HBcAB+HBV DNA above the LLOQ) To remain eligible for the study, the participant’s HBV DNA levels must remain below the LLOQ as per the central lab\n- Active hepatitis C infection (defined as positive hepatitis C virus antibody and detectable HCV ribonucleotide (RNA) as confirmed by central lab\n- Any severe case of HZ infection at any time prior to Week 0 (Day 1)\n- Any clinical CMV or EBV infection that has not completely resolved within 12 weeks prior to the ICF"}

Primary endpoints

• {"endpoint_text":"- \"CRR at Week 52, ie, meeting all of the following: - UPCR ≤ 0.5 mg/mg - eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline of ≥ 20%\"","definition_or_measurement_approach":"Defined in the endpoint text: CRR at Week 52 requires UPCR ≤ 0.5 mg/mg and eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline of ≥ 20%."}

Secondary endpoints

• {"endpoint_text":"- \"Sustained OCS reduction, ie, meeting all of the following: - OCS dose of ≤ 7.5 mg/day prednisone or equivalent by Week 24 - Sustained OCS dose of ≤ 7.5 mg/day prednisone or equivalent from Week 24 through Week 52\"","definition_or_measurement_approach":"Defined in the endpoint text: OCS dose reduced to ≤7.5 mg/day prednisone (or equivalent) by Week 24 and maintained from Week 24 through Week 52."}
• {"endpoint_text":"- \"Time to sustained CRR, ie, meeting all of the following: - UPCR ≤ 0.5 mg/mg - eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline of ≥ 20% (ie, time from first study intervention dose to achieving CRR that is sustained from that time point through Week 52)\"","definition_or_measurement_approach":"Defined in the endpoint text: time from first study dose to achieving CRR (UPCR ≤0.5 mg/mg and eGFR criteria) that is sustained through Week 52."}
• {"endpoint_text":"- Cumulative UPCR as determined by the standardized AUC from baseline up to and including Week 52.","definition_or_measurement_approach":"UPCR cumulative exposure measured as standardized area under the curve (AUC) from baseline through Week 52."}
• {"endpoint_text":"- CRR at Week 24 (see definition above)","definition_or_measurement_approach":"CRR defined as UPCR ≤0.5 mg/mg and eGFR ≥60 mL/min/1.73 m2 or no decrease from baseline ≥20%, assessed at Week 24."}
• {"endpoint_text":"- Time to renal event as defined as any of the following: 1) ESKD, 2) doubling of serum creatinine, 3) renal worsening as evidenced by increased proteinuria and/or renal function impairment, or 4) renal disease treatment failure, or 5) death - through Week 52.","definition_or_measurement_approach":"Time from baseline to first occurrence of a renal event defined as ESKD, doubling of serum creatinine, renal worsening (increased proteinuria and/or renal impairment), renal treatment failure, or death through Week 52."}
• {"endpoint_text":"- Time to renal-related event or death (see definition above) through Week 76","definition_or_measurement_approach":"Time from baseline to renal-related event or death as defined for renal event endpoints, assessed through Week 76."}

Methods

• Country-specific recruitment arrangements documents (K1_Recruitment arrangements) uploaded for multiple member states indicating use of site-based recruitment.
• Printed recruitment materials: leaflets and pamphlets (K2_Recruitment material_leaflet / pamphlet) for patient-facing distribution.
• Posters and study brochures (K2_Recruitment material Poster / study brochure).
• Web advertisement copy provided (K2_Recruitment material_advertisement text web / advertisement text print) indicating online recruitment channels.

Bulgaria

Latest Decision Or Authorization Date

17-05-2024

Number Of Sites

3

Number Of Participants

4

Hungary

Latest Decision Or Authorization Date

21-05-2024

Number Of Sites

4

Number Of Participants

16

Italy

Latest Decision Or Authorization Date

21-05-2024

Number Of Sites

7

Number Of Participants

8

Netherlands

Latest Decision Or Authorization Date

16-05-2024

Number Of Sites

1

Number Of Participants

3

France

Latest Decision Or Authorization Date

16-05-2024

Number Of Sites

9

Number Of Participants

12

Poland

Latest Decision Or Authorization Date

14-06-2024

Number Of Sites

9

Number Of Participants

8

Belgium

Latest Decision Or Authorization Date

17-05-2024

Number Of Sites

3

Number Of Participants

6

Germany

Latest Decision Or Authorization Date

22-05-2024

Number Of Sites

8

Number Of Participants

12

Primary sponsor

Full Name

Astrazeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden