Rozibafusp Alfa for SLE

No longer recruiting at 197 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

Must be taking: Anti-malarials, Immunosuppressants

Disqualifiers: Active CNS lupus, High proteinuria, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Rozibafusp Alfa, an experimental treatment, to determine its effectiveness for people with systemic lupus erythematosus (SLE), particularly those with persistent symptoms despite standard treatments. Participants will receive varying doses of Rozibafusp Alfa or a placebo to compare effects. The trial seeks individuals diagnosed with SLE who experience active joint pain or swelling and have not fully responded to standard treatments like hydroxychloroquine or methotrexate. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

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

Research has shown that Rozibafusp Alfa is generally well tolerated. In studies, 96.2% of patients taking Rozibafusp Alfa experienced treatment-related side effects, but most were mild or moderate, indicating they were not very serious. For comparison, 87.5% of patients taking a placebo (a harmless, inactive substance) also experienced similar mild or moderate side effects.

Rozibafusp Alfa is considered safe for individuals with active systemic lupus erythematosus (SLE), a condition where the immune system attacks the body's own tissues. Although it did not consistently show significant improvement over standard treatments, its safety profile is reassuring. Most participants did not encounter serious issues while on the treatment, making it a potential option worth considering. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Rozibafusp Alfa is unique because it targets a specific pathway involved in systemic lupus erythematosus (SLE) by modulating the activity of both B cells and T cells. Unlike traditional treatments for SLE, which often include corticosteroids and immunosuppressants that broadly dampen the immune system, Rozibafusp Alfa aims to be more precise in its action. This specificity has the potential to reduce disease activity while minimizing side effects. Researchers are excited about Rozibafusp Alfa because it represents a more targeted approach, which could lead to better management of SLE with fewer complications.

What evidence suggests that Rozibafusp Alfa could be an effective treatment for SLE?

Research has shown that Rozibafusp Alfa is a new treatment being tested for systemic lupus erythematosus (SLE). Earlier studies found that it effectively targets a specific part of the immune system, crucial for its function. Rozibafusp Alfa is designed to affect both T-cells and B-cells, which play roles in the immune response in SLE. However, some studies suggest it may not offer significantly more benefit than standard SLE treatments. Despite this, it has been found safe and well-tolerated by patients. Therefore, Rozibafusp Alfa could still be a promising option for those whose disease remains active despite current treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Rozibafusp Alfa

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 (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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9555197/

Safety and Biological Activity of Rozibafusp alfa, a Bispecific ... The current results showed that multiple doses of rozibafusp alfa achieved greater than 90% mean ICOSL RO in the 210‐ and 420‐mg dose cohorts.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04058028

NCT04058028 | Efficacy and Safety of AMG 570 in ... The purpose of this study is to determine if Rozibafusp Alfa could be a useful therapeutic agent in the current treatment landscape where subjects with SLE have ...

3. jrheum.org jrheum.org/content/52/Suppl_1/73

ROZIBAFUSP ALFA IN PATIENTS WITH ACTIVE ... Rozibafusp alfa did not show substantial added benefit over SOC for SLE treatment. Rozibafusp alfa was safe and well tolerated in patients with active SLE.

4. amgentrials.com amgentrials.com/study/?id=20170588

Efficacy and Safety of AMG 570 in Subjects With Active ... The purpose of this study is to determine if Rozibafusp Alfa could be a useful therapeutic agent in the current treatment landscape where subjects with SLE have ...

5. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.2929

Pharmacokinetics and Pharmacokinetic/Pharmacodynamic ... Rozibafusp alfa (AMG 570) is a first-in-class bispecific IgG2-peptide fusion designed to inhibit inducible T-cell costimulator ligand (ICOSL) and B-cell ...

6. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/acr2.11487

Safety and Biological Activity of Rozibafusp alfa, a Bispecific ... TEAEs occurred in 96.2% and 87.5% of patients receiving rozibafusp alfa and the placebo, respectively; most were mild or moderate in severity.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496724676600

Scientific Abstracts FRI0084 SAFETY, ... As of June 5, 2019, 34 subjects were enrolled and included in this interim analysis. Rozibafusp alfa was generally well tolerated. TEAEs occurred in 92.3% and ...