Felzartamab for Antibody Mediated Rejection

(TRANSCEND Trial)

Recruiting at 65 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called felzartamab for individuals who have undergone a kidney transplant and are experiencing antibody-mediated rejection (AMR). The trial aims to compare the effectiveness of felzartamab to a placebo in assisting these kidney transplant recipients. Participants must have received their transplant at least six months prior and have a specific type of rejection confirmed by biopsy. This trial may suit those facing ongoing issues with their kidney transplant and have certain antibodies present. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

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.

Is there any evidence suggesting that felzartamab is likely to be safe for humans?

Research has shown that felzartamab is generally safe for patients experiencing antibody-mediated rejection. In earlier studies, most side effects were mild to moderate, indicating they were not very serious. These findings suggest that felzartamab is usually well-tolerated by individuals who have undergone kidney transplants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AMR?

Unlike standard treatments for antibody-mediated rejection, which often rely on broad immunosuppressants, Felzartamab offers a more targeted approach. This experimental drug is designed to specifically deplete CD38-positive plasma cells, which play a critical role in antibody production. By honing in on these cells, Felzartamab has the potential to reduce harmful antibodies more effectively, minimizing the need for generalized immune suppression. Researchers are excited about Felzartamab because it could offer a more precise treatment, potentially leading to better outcomes with fewer side effects.

What evidence suggests that felzartamab might be an effective treatment for AMR?

Research has shown that felzartamab, a monoclonal antibody, may help treat kidney transplant rejection caused by antibodies. In this trial, some participants will receive felzartamab, while others will receive a placebo. Studies have found that felzartamab can reduce the activity of this rejection, both in physical symptoms and lab tests. Patients generally tolerate the treatment well, experiencing side effects similar to those seen when used for other conditions like multiple myeloma. Although results have varied, the potential benefits suggest that felzartamab could be useful for managing certain types of rejection in kidney transplant patients. ^{4 5 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8990453/

Safety, tolerability, and efficacy of monoclonal CD38 antibody ... Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05021484

NCT05021484 | Felzartamab in Late Antibody-Mediated ... This prospective trial will assess the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics and efficacy of the fully human CD38 monoclonal ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/13543784.2025.2463092

Full article: CD38 monoclonal antibody felzartamab for late ... Efficacy outcomes suggested potential therapeutic benefits, including significant reductions in morphologic and molecular AMR activity. Given the mixed results ...

4. kidney-international.org kidney-international.org/article/S0085-2538(25)00488-0/fulltext

Randomized, double-blind, placebo-controlled phase 2a ... Felzartamab was generally well tolerated and had a safety profile consistent with that of felzartamab in patients with antibody-mediated kidney transplant ...

5. frontierspartnerships.org frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.14343/full

Targeting CD38 in Antibody-Mediated Rejection Felzartamab (MOR202; IgG1λ) has shown efficacy in relapsed or refractory multiple myeloma [38], and is now being developed for autoimmune ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38804514/

A Randomized Phase 2 Trial of Felzartamab in Antibody- ... Conclusions: Felzartamab had acceptable safety and side-effect profiles in patients with antibody-mediated rejection. (Funded by MorphoSys ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06685757

Study Details | NCT06685757 | A Trial of Felzartamab in ... 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 ...

8. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06198-9

Safety, tolerability, and efficacy of monoclonal CD38 antibody ... Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol ...