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

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05097989

Collaborator

(none)

126

Enrollment

Locations

Arms

55.3

Anticipated Duration (Months)

25.2

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis Immunoglobulin A Nephropathy IgAN LN	Drug: ALXN2050 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

126 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Masking of treatment allocation will be observed at least until Week 50.

Primary Purpose:

Treatment

Official Title:

A Phase 2, Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Efficacy and Safety of ALXN2050 in Adult Participants With Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

Actual Study Start Date :

Jan 14, 2022

Anticipated Primary Completion Date :

Jan 5, 2024

Anticipated Study Completion Date :

Aug 24, 2026

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: ALXN2050 Oral tablets Other Names: ACH-0145228 (formerly)
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.	Drug: ALXN2050 Oral tablets Other Names: ACH-0145228 (formerly)
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.	Drug: Placebo Oral tablets
Experimental: IgAN Cohort: ALXN2050 180 mg Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050 Oral tablets Other Names: ACH-0145228 (formerly)
Experimental: IgAN Cohort: ALXN2050 120 mg Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050 Oral tablets Other Names: ACH-0145228 (formerly)
Placebo Comparator: IgAN Cohort: Placebo Participants diagnosed with IgAN will receive matched placebo in addition to standard-of-care background therapy.	Drug: Placebo Oral tablets

Outcome Measures

Primary Outcome Measures

Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26 [Baseline, Week 26]
This will be based on 24-hour urine collection(s).

Secondary Outcome Measures

Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 50 [Baseline, Week 50]
This will be based on 24-hour urine collection(s).
Both Cohorts: Participants Achieving > 30% And > 50% Reduction In Proteinuria At Week 26 And Week 50 Compared To Baseline [Baseline, Week 26 and Week 50]
This will be based on 24-hour urine collection(s) at each time point.
Both Cohorts: Change From Baseline In Estimated Glomerular Filtration Rate (eGFR) At Week 26 And Week 50 [Baseline, Week 26 and Week 50]
LN Cohort: Participants Meeting The Criteria For Complete Renal Response At Week 26 And Week 50 [Week 26 And Week 50]
LN Cohort: Participants Meeting The Criteria For Partial Renal Response At Week 26 And Week 50 [Week 26 And Week 50]
LN Cohort: Time To The First Occurrence Of Urine Protein To Creatinine Ratio (UPCR) ≤ 0.5 Gram/Gram (g/g) As Measured By Spot Urine Sample [Up to Week 50]
LN Cohort: Participants Achieving Corticosteroid Taper To 7.5 mg/Day At Weeks 12, 26, And 50 [Week 12, Week 26, And Week 50]
LN Cohort: Participants Experiencing A Renal Flare Through Week 50 [Baseline through Week 50]
LN Cohort: Participants Experiencing An Extrarenal Systemic Lupus Erythematosus (SLE) Flare Through Week 50 [Baseline through Week 50]
LN Cohort: Participants Meeting The Criteria For Treatment Failure Through Week 50 [Baseline through Week 50]
LN Cohort: Absolute Values And Change From Baseline In Serum Albumin At Week 26 And Week 50 [Baseline, Week 26 and Week 50]
IgAN Cohort: Participants Meeting The Criteria For Partial Remission At Week 26 And Week 50 [Week 26 and Week 50]
Both Cohorts: Observed Plasma Concentrations Of ALXN2050 Over Time [Baseline through Week 50]
Both Cohorts: Absolute Values And Change From Baseline In Plasma Concentration Of Bb Fragment Of Complement Factor B At Week 50 [Baseline, Week 50]
Both Cohorts: Absolute Values And Change From Baseline In Serum Alternative Pathway Activity At Week 50 [Baseline, Week 50]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

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.
Presence of hematuria as defined by 1+ blood based on urine dipstick or ≥ 10 red blood cells/high power field microscopy on urine sediment (performed by the local laboratory) during Screening Period (only applicable if diagnostic biopsy is >2 years prior to Screening).
Compliance with stable and optimal dose of RAS inhibitor treatment including maximum allowed or tolerated angiotensin converting enzyme inhibitor and/or angiotensin receptor blocker dose for ≥ 3 months prior to Screening with no expected change in dose during the study (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.
More than or equal to 50% interstitial fibrosis, tubular atrophy, glomerular sclerosis, or crescent formation in glomeruli on most recent kidney biopsy prior or during the Screening Period.
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 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).

For LN Cohort

Participants who have received any of the following treatments:

Cyclophosphamide ≤ 6 months prior to Screening
Calcineurin inhibitors ≤ 3 months prior to Screening
A cumulative dose of intravenous methylprednisolone > 3 g for the current active renal flare
Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 4 consecutive weeks prior to Screening for the current active renal flare
Prednisone or prednisone equivalent ≥ 0.5 mg/kilogram/day for ≥ 4 consecutive weeks prior to Screening for the current active renal flare

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

For 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 for > 14 consecutive days or any other immunosuppression within 6 months prior to Screening.
Blood pressure of ≥ 140/90 mmHg during the Screening Period confirmed on 2 measures > 30 minutes apart.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Huntsville	Alabama	United States	35805-4104
2	Clinical Trial Site	Northridge	California	United States	91324-3138
3	Clinical Trial Site	Northridge	California	United States	91324-3528
4	Clinical Trial Site	Vacaville	California	United States	95687
5	Clinical Trial Site	Kansas City	Missouri	United States	64111-2925