ALXN2050 for Kidney Disease

No longer recruiting at 192 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alexion Pharmaceuticals, Inc.

Must be taking: SGLT 2 inhibitors, RAS inhibitors

Must not be taking: Cyclophosphamide, CNIs, Prednisone

Disqualifiers: eGFR ≤ 30, Transplant history, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, ALXN2050, for two types of kidney disease: Lupus Nephritis (LN) and IgA Nephropathy (IgAN). The researchers aim to determine if ALXN2050 can improve symptoms of these conditions more effectively than a placebo. Participants will continue their usual treatments while receiving either ALXN2050 or a placebo. Those diagnosed with LN experiencing an active flare, or with IgAN and significant protein in their urine, might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify that you need to stop your current medications. However, if you are on sodium-glucose cotransporter-2 (SGLT 2) inhibitors or RAS inhibitors, you must be on a stable dose for at least 3 months before and during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ALXN2050, a pill that blocks a protein linked to inflammation, is being tested for safety in treating kidney diseases like lupus nephritis (LN) and IgA nephropathy (IgAN). Earlier studies found that patients generally tolerate this treatment well, though some participants experienced mild to moderate side effects, which are common for such treatments.

The current research phase is crucial for assessing how well people can handle the treatment. This step determines if the treatment is safe enough for wider use. While no treatment is perfect, ALXN2050 appears promising in terms of safety, as trials have reported no major safety issues so far. However, researchers will closely monitor participants to ensure their safety throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ALXN2050 because it offers a new approach to treating kidney diseases like lupus nephritis (LN) and IgA nephropathy (IgAN). Unlike the standard treatments, which often involve corticosteroids and immunosuppressants, ALXN2050 specifically targets and inhibits the complement pathway, a part of the immune system involved in inflammation and tissue damage. This novel mechanism of action could lead to more effective control of disease flares with potentially fewer side effects. Additionally, ALXN2050 is being investigated at different dosages to optimize its effectiveness and safety for patients.

What evidence suggests that ALXN2050 might be an effective treatment for kidney disease?

This trial will evaluate ALXN2050 for treating lupus nephritis (LN) and IgA nephropathy (IgAN). Participants in different arms of the trial will receive either ALXN2050 at varying doses or a placebo, alongside standard-of-care background therapy. Research suggests that ALXN2050 blocks a protein called complement factor D, which causes inflammation and kidney damage. Earlier studies have shown that this method can lower protein levels in urine, an important indicator of kidney disease. For LN, some studies have found that similar treatments can improve kidney function and reduce disease symptoms. For IgAN, ALXN2050 aims to prevent worsening kidney damage, which is crucial as this disease often leads to long-term kidney failure. Although more research is needed, these early results are promising. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Adults aged 18-75 with Lupus Nephritis (LN) or IgA Nephropathy (IgAN), who meet specific diagnostic criteria, including certain levels of proteinuria and active disease requiring treatment. Participants must have stable blood pressure and kidney function, and not be planning a transplant or have other significant health issues.

Inclusion Criteria

I have lupus with kidney involvement, confirmed by a recent biopsy, and need strong medication.

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 mmHg) over the past 3 months prior to randomization.

I have been on a stable dose of SGLT2 inhibitors for 3 months or more.

Exclusion Criteria

LN Cohort: Participants who have initiated any of the following treatments for the current active LN flare: Cyclophosphamide ≤ 6 months prior to Screening, CNIs ≤ 1 month prior to Screening, a cumulative dose of intravenous (IV) methylprednisolone > 3 g, Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 8 consecutive weeks prior to Screening, 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.

My kidney function is severely reduced, and my recent biopsy shows significant damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 6 weeks

Initial Evaluation

Participants receive blinded treatment with ALXN2050 or placebo for initial evaluation

26 weeks

Extended Treatment

Participants continue blinded treatment with ALXN2050 or placebo

24 weeks

Open-label Extension

Participants may opt into continuation of treatment with ALXN2050 long-term

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALXN2050

Trial Overview The trial is testing ALXN2050 at two doses versus placebo in addition to standard care for LN or IgAN. It includes an initial evaluation period of 26 weeks, followed by an extended treatment period of 24 weeks, with the possibility of joining a longer open-label extension study.

How Is the Trial Designed?

Group I: LN Cohort: ALXN2050 180 mg Experimental Treatment 1 Intervention

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

Group II: LN Cohort: ALXN2050 120 mg Experimental Treatment 1 Intervention

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

Group III: IgAN Cohort: ALXN2050 180 mg Experimental Treatment 1 Intervention

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

Group IV: IgAN Cohort: ALXN2050 120 mg Experimental Treatment 1 Intervention

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

Group V: LN Cohort: Placebo Placebo Group 1 Intervention

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

Group VI: IgAN Cohort: Placebo Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Alexion Pharmaceuticals

Lead Sponsor

Trials

231

Recruited

36,700+

Marc Dunoyer

Alexion Pharmaceuticals

Chief Executive Officer since 2021

B.A. in Psychology from the University of New Hampshire

Christophe Hotermans

Alexion Pharmaceuticals

Chief Medical Officer since 2023

MD

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2468024923001742

WCN23-0141 A PHASE 2 STUDY EVALUATING THE ... This global, multicenter, phase 2 study (NCT05097989) will evaluate the efficacy and safety of ALXN2050, an oral, small molecule complement factor D inhibitor, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05097989

Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or ... This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study of ALXN2050 (120 and 180 milligrams [mg]) in addition to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10889409/

An Update on Current Therapeutic Options in IgA Nephropathy Immunoglobulin A nephropathy (IgAN) remains the leading cause of primary glomerular disease worldwide. Outcomes are poor with high rates of ...

4. kireports.org kireports.org/article/S2468-0249(23)00174-2/pdf

WCN23-0141 A PHASE 2 STUDY EVALUATING THE ... This global, multicenter, phase 2 study (NCT05097989) will evaluate the efficacy and safety of. ALXN2050, an oral, small molecule complement factor D inhibitor, ...

5. academic.oup.com academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfaf167/8238644

Targeted therapeutic options based on the pathogenesis of ... The disease often results in progressive chronic kidney disease and eventual kidney failure, and has a poor prognosis, significantly increasing ...

6. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/clinicaltrial/2132/phase-2-randomized-double-blind/

Clinical Research Studies - NYU This is a phase 2, randomized, double-blind, placebo-controlled, dose-finding study to evaluate the efficacy and safety of ALXN2050, an oral complement FD ...