Felzartamab for Antibody Mediated Rejection

(TRANSCEND Trial)

Recruiting at 23 trial locations

Overseen By Global Biogen Clinical Trial Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: HI-Bio, A Biogen Company

Must not be taking: Immunoglobulins, Complement inhibitors

Disqualifiers: ABO-incompatible transplant, Multiple organ transplants, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have received certain treatments for AMR in the past 3 to 6 months, you may need to have additional tests to confirm eligibility.

What makes the drug Felzartamab unique for treating antibody-mediated rejection?

Felzartamab is unique because it targets CD38, a protein on the surface of certain immune cells, which may help reduce the harmful antibodies causing rejection. This mechanism is different from other treatments like tocilizumab and bortezomib, which target different pathways in the immune system. ^{1 2 3 4 5}

What is the purpose of this trial?

The main goal of this trial is to evaluate the efficacy of felzartamab compared to placebo in kidney transplant recipients diagnosed with late active or chronic active AMR.

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

This trial is for kidney transplant recipients who are experiencing late active or chronic active antibody-mediated rejection (AMR). Specific eligibility criteria details were not provided, so it's important to consult the study team for more information.

Inclusion Criteria

Active or chronic active AMR (biopsy-confirmed) without TCMR per central reading, as defined by the Banff 2022 criteria

I had a kidney transplant more than 6 months ago.

I have antibodies against my transplant as confirmed by a test in the last 6 months.

Exclusion Criteria

I have had more than one organ transplant.

I am receiving a transplant from a donor with a different blood type.

My kidney function is rapidly declining, and I might need dialysis soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either felzartamab or placebo to evaluate efficacy in treating late antibody-mediated rejection in kidney transplant recipients

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Felzartamab

Trial Overview The trial aims to assess how effective felzartamab is compared to a placebo in treating AMR in those who have received a kidney transplant. Participants will be randomly assigned to receive either felzartamab or a placebo.

Participant Groups

Group I: Felzartamab Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

HI-Bio, A Biogen Company

Lead Sponsor

Trials

7

Recruited

300+

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Findings from Research

In a small observational study of 5 renal transplant patients with chronic active antibody-mediated rejection (cAMR), treatment with tocilizumab (TCZ) did not stabilize renal function or reduce donor-specific HLA antibodies (DSAs).

Despite administering TCZ, there was no improvement in inflammation of microcirculation or transplant glomerulopathy, indicating that TCZ may not be an effective treatment for cAMR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in the treatment of active chronic humoral rejection resistant to standard therapy. Chamoun, B., Sánchez-Sancho, P., Torres, IB., et al.[2023]

Bortezomib showed potential in improving renal function in two sensitized transplant recipients experiencing antibody-mediated rejection that was resistant to other treatments like intravenous immunoglobulin and plasmapheresis.

While bortezomib treatment led to some changes in antibody levels, the results were mixed, indicating a need for further research to understand its long-term effects on HLA removal and graft function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib for acute humoral rejection in two repeat transplant recipients. Hardinger, KL., Alford, K., Murillo, D.[2015]

Tocilizumab (TCZ) treatment in 12 patients with chronic antibody-mediated rejection (cAMR) significantly reduced total IgG and IgG1-3 levels, indicating its potential to suppress antibody production in B cells.

The reduction in anti-HLA-total IgG and IgG3 levels in 73% of patients suggests that TCZ may effectively target the underlying mechanisms of cAMR, likely through inhibition of interleukin 6 signaling, which could contribute to its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Tocilizumab (Anti-IL-6R) Treatment on Immunoglobulins and Anti-HLA Antibodies in Kidney Transplant Patients With Chronic Antibody-mediated Rejection. Shin, BH., Everly, MJ., Zhang, H., et al.[2021]

In a study of 11 kidney transplant recipients with chronic active antibody-mediated rejection (ca-AMR), treatment with tocilizumab (TCZ) led to a significant reduction in donor-derived cell-free DNA (dd-cfDNA), indicating decreased graft injury, with 8 out of 11 patients achieving dd-cfDNA levels below 1% after 6 months.

TCZ treatment also stabilized donor-specific antibodies (DSA) and maintained stable graft function without any graft loss, although two patients experienced moderate to severe infections during the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for treatment of chronic active antibody-mediated rejection in kidney transplant recipients. Boonpheng, B., De Castro, ICC., Ng, YH., et al.[2023]

Bortezomib showed promising results in treating humoral rejection in four transplant recipients, with all patients experiencing improved renal function and three out of four showing negative biopsy results for c4d, indicating a reduction in rejection.

No significant adverse drug events were reported, although two patients did experience infections, suggesting that bortezomib may be a safe option for patients with refractory antibody-mediated rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib as rescue therapy for antibody mediated rejection: a single-center experience. Hardinger, KL., Alford, K., Murillo, D.[2015]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Tocilizumab in the treatment of active chronic humoral rejection resistant to standard therapy. [2023]

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

Bortezomib for acute humoral rejection in two repeat transplant recipients. [2015]

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

Impact of Tocilizumab (Anti-IL-6R) Treatment on Immunoglobulins and Anti-HLA Antibodies in Kidney Transplant Patients With Chronic Antibody-mediated Rejection. [2021]

4. Denmark pubmed.ncbi.nlm.nih.gov

Tocilizumab for treatment of chronic active antibody-mediated rejection in kidney transplant recipients. [2023]

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

Bortezomib as rescue therapy for antibody mediated rejection: a single-center experience. [2015]