Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

Study Purpose

This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study of ALXN2050 (120 and 180 milligrams [mg]) in addition to background therapy consistent with the standard of care in adult participants (≥ 18 to ≤ 75 years of age) with either LN or IgAN. The study will consist of an up to 6-week Screening Period, a 26-week blinded Initial Evaluation Period, a 24-week blinded Extended Treatment Period, and an Open-label Extension (OLE) Period of up to 2 years. Safety will be monitored throughout the study.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 75 Years
Gender	All

More Inclusion & Exclusion Criteria

Key

Inclusion Criteria:

Both Cohorts.

- Participants on sodium-glucose cotransporter-2 (SGLT 2) inhibitors (eg, empagliflozin) must be on a stable dose for ≥ 3 months with no planned change in dose during the Blinded Treatment Periods (through Week 50).

LN Cohort.

- Clinical diagnosis of SLE by 2019 American College of Rheumatology and European League Against Rheumatism criteria.

- Diagnosis of 2018 Revised International Society of Nephrology/Renal Pathology Society classification (active focal or diffuse proliferative LN Class III or IV) confirmed by biopsy obtained ≤ 6 months prior to Screening or during Screening Period.

Participants may co-exhibit Class V disease. Participants with de novo or relapsing disease may be eligible.

- Clinically active LN at Screening requiring/receiving immunosuppression induction treatment in the opinion of the Investigator.

- Proteinuria with UPCR ≥ 1 g/g based on one 24 hour urine collection during the Screening Period.

IgAN Cohort.

- Established diagnosis of primary IgAN based on kidney biopsy obtained any time prior to or during the Screening Period.

- Mean proteinuria ≥ 1 g/day on 2 complete and valid 24 hour urine collections during the Screening Period.

- For participants with a kidney biopsy performed > 1 year prior to Screening that was used for eligibility: Presence of hematuria as defined by a positive result for blood on urine dipstick or ≥ 10 red blood cells (RBCs)/high power field (hpf) microscopy on urine sediment (documented by the local laboratory) during Screening Period.

Presence of hematuria documented by the central laboratory may also be acceptable.

- Compliance with stable and optimal dose of RAS inhibitor treatment including maximum allowed or tolerated ACE inhibitor and/or ARB dose for ≥ 3 months prior to Screening with no expected change in dose during the Blinded Treatment Periods (through Week 50) (participants with established intolerance to RAS inhibitors may be included).

- Controlled and stable blood pressure (defined as < 140/90 millimeters of mercury [mmHg]) over the past 3 months prior to randomization.

Key

Exclusion Criteria:

Both Cohorts.

- eGFR ≤ 30 milliliters/minute/1.73 squared meters during Screening calculated by Chronic Kidney Disease Epidemiology Collaboration.

- For participants with eGFR < 45 mL/min/1.73 m2 at Screening, presence of any of the following in glomeruli on most recent kidney biopsy prior to or during the Screening.

Period: 1. ≥ 50% interstitial fibrosis and tubular atrophy. 2. ≥ 50% glomerular sclerosis. 3. ≥ 50% active crescent formation.

- Concomitant significant renal disease other than LN or IgAN on the most recent biopsy prior to or during the Screening Period.

- History of solid organ or bone marrow transplant, or planned transplant during the Blinded Extended Treatment Period (50 weeks).

- Splenectomy or functional asplenia.

- Known or suspected complement deficiency, unless attributable to underlying disease (that is, LN and IgAN).

- Bone marrow insufficiency with absolute neutrophil count < 1.3 × 10^3/microliter; thrombocytopenia (platelet count < 50,000/cubic millimeter).

LN Cohort.

- Participants who have initiated any of the following treatments for the current active LN flare: 1.

Cyclophosphamide ≤ 6 months prior to Screening. 2. CNIs ≤ 1 months prior to Screening. 3. A cumulative dose of intravenous (IV) methylprednisolone > 3 g. 4. Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 8 consecutive weeks prior to Screening. 5. Prednisone or prednisone equivalent ≥ 0.5 mg/kg/day for ≥ 8 consecutive weeks prior to Screening.

- Uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 110 mmHg) on 2 or more measurements during the Screening Period.

- Prior history or clinically active SLE-related cerebritis, seizures, stroke, or stroke syndrome requiring treatment or clinically active pericarditis.

- Inability to take or tolerate the standard of care background therapies.

IgAN Cohort.

- Diagnosis of rapid progressive glomerulonephritis as measured by eGFR loss ≥ 30% over a period of 3 months prior to or during the Screening Period.

- Secondary etiologies of IgAN.

- Prednisone or prednisone equivalent > 20 mg/day for > 14 consecutive days or any other systemic immunosuppression for the treatment of IgAN ≤ 6 months prior to Screening.

- Blood pressure of ≥ 140/90 mmHg during the Screening Period confirmed on 2 measures > 30 minutes apart.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05097989
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Alexion Pharmaceuticals, Inc.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Australia, Brazil, China, Germany, Israel, Italy, Korea, Republic of, Mexico, Peru, Russian Federation, Serbia, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Lupus Nephritis, Immunoglobulin A Nephropathy, IgAN, LN

Arms & Interventions

Arms

Experimental: LN Cohort: ALXN2050 180 mg

Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.

Experimental: LN Cohort: ALXN2050 120 mg

Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.

Placebo Comparator: LN Cohort: Placebo

Participants diagnosed with LN with an active flare will receive matched placebo in addition to standard-of-care background therapy.

Experimental: IgAN Cohort: ALXN2050 180 mg

Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.

Experimental: IgAN Cohort: ALXN2050 120 mg

Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.

Placebo Comparator: IgAN Cohort: Placebo

Participants diagnosed with IgAN will receive matched placebo in addition to standard-of-care background therapy.

Interventions

Drug: - ALXN2050

Oral tablets

Drug: - Placebo

Oral tablets

Contact a Trial Team

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Research Site, Huntsville, Alabama

Status

Recruiting

Address

Research Site

Huntsville, Alabama, 35805

Site Contact

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