Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)

Recruiting at 154 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

244 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Rozibafusp Alfa to see if it can help patients with active SLE who haven't improved with standard treatments. The medication works by calming the overactive immune system. Rozibafusp Alfa is a new treatment being tested for systemic lupus erythematosus (SLE).

Will I have to stop taking my current medications?

The trial requires that you continue taking certain SLE treatments, such as anti-malarials or other specified medications, for at least 12 weeks before screening and maintain a stable dose for at least 8 weeks. If you're on oral corticosteroids, the dose must be stable and not exceed 20 mg/day of prednisone or its equivalent.

What data supports the effectiveness of the drug Rozibafusp Alfa?

Rozibafusp Alfa has shown effectiveness in reducing certain immune cells in patients with rheumatoid arthritis, which suggests it may help in conditions involving the immune system. It works by targeting specific proteins that play a role in immune responses, and this mechanism has been studied in early clinical trials. ^{1 2 3 4 5}

How is the drug Rozibafusp Alfa different from other treatments for autoimmune conditions?

Rozibafusp Alfa is unique because it is a first-in-class bispecific inhibitor that targets both the inducible T-cell costimulator ligand (ICOSL) and B-cell activating factor (BAFF), which are involved in immune system regulation. This dual-target approach is different from other treatments that typically focus on a single pathway, potentially offering a more comprehensive modulation of the immune response. ^{1 2 6 7 8}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

Inclusion Criteria

You have a high score on a test that measures the severity of your lupus symptoms, and your symptoms are mostly related to how you feel rather than test results.

You have provided informed consent prior to any study-specific activities/procedures.

Scleritis and Episcleritis: the presence of stable SLE-related scleritis and episcleritis must be documented by an ophthalmologist and other causes excluded.

Exclusion Criteria

You have experienced certain serious brain or nervous system conditions within the past year, such as meningitis, difficulty with coordination, inflammation of blood vessels in the brain, nerve damage, vision problems, mental health issues, seizures, or spinal cord inflammation.

Urine protein creatinine ratio ≥ 3000 mg/g (or equivalent) at screening or induction therapy for lupus nephritis within 1 year prior to screening visit.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rozibafusp Alfa or placebo in a double-blind, randomized, placebo-controlled setting for dose-ranging over 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Treatment Details

Interventions

• Rozibafusp Alfa

Participant Groups

Group I: Rozibafusp Alfa, Dose C Experimental Treatment 1 Intervention

Investigational product solution in vial

Group II: Rozibafusp Alfa, Dose B Experimental Treatment 1 Intervention

Investigational product solution in vial

Group III: Rozibafusp Alfa, Dose A Experimental Treatment 1 Intervention

Investigational product solution in vial

Group IV: Placebo for Rozibafusp Alfa Placebo Group 1 Intervention

Placebo Investigational product solution in vial

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

Rozibafusp alfa, a bispecific antibody-peptide conjugate, was well tolerated in a phase 1b study with 34 patients suffering from rheumatoid arthritis, showing that most treatment-emergent adverse events were mild or moderate in severity.

The treatment demonstrated significant biological activity, with dose-related effects on immune cell populations and greater improvements in rheumatoid arthritis disease activity compared to placebo, particularly in higher dose cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Biological Activity of Rozibafusp alfa, a Bispecific Inhibitor of Inducible Costimulator Ligand and B Cell Activating Factor, in Patients With Rheumatoid Arthritis: Results of a Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study. Abuqayyas, L., Cheng, LE., Teixeira Dos Santos, M., et al.[2022]

Bintrafusp alfa, a novel treatment for advanced solid tumors, demonstrated a manageable safety profile and clinical activity in phase I studies involving heavily pretreated patients.

The recommended phase 2 dose of bintrafusp alfa is 1,200 mg every 2 weeks or 2,400 mg every 3 weeks, which effectively maintains drug levels that inhibit its targets in over 95% of patients, with exposure showing a weak correlation to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection of the Recommended Phase 2 Dose for Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1. Vugmeyster, Y., Wilkins, J., Koenig, A., et al.[2021]

In a study involving 83 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone anti-PD-(L)1 therapy, bintrafusp alfa demonstrated a modest objective response rate of 4.8%, indicating some clinical activity despite not meeting the primary endpoint.

The treatment was generally well-tolerated, with 22.9% of patients experiencing grade ≥3 treatment-related adverse events, suggesting a manageable safety profile for this heavily pretreated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors. Barlesi, F., Isambert, N., Felip, E., et al.[2023]

Bintrafusp alfa (BA) effectively enhances antitumor activity by simultaneously targeting PD-L1 and TGF-β in the tumor microenvironment, leading to a significant increase in binding affinity and improved T cell activation compared to traditional therapies.

BA induces distinct changes in the tumor microenvironment, including upregulation of immune-related gene signatures and reduction of TGF-β-regulated pathways, resulting in superior antitumor responses over standard combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses. Lan, Y., Yeung, TL., Huang, H., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Properties of Rozibafusp Alfa, a Bispecific Inhibitor of BAFF and ICOSL: Analyses of Phase I Clinical Trials. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and Biological Activity of Rozibafusp alfa, a Bispecific Inhibitor of Inducible Costimulator Ligand and B Cell Activating Factor, in Patients With Rheumatoid Arthritis: Results of a Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Selection of the Recommended Phase 2 Dose for Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Tebentafusp in Patients with Metastatic Uveal Melanoma: A Real-Life Retrospective Multicenter Study. [2023]