ABBV-383 for Amyloidosis

Recruiting at 25 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AbbVie

Must be taking: Proteasome inhibitors, Anti-CD38 antibodies

Disqualifiers: Multiple myeloma, Plasma cell leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, Etentamig (ABBV-383), for people with AL amyloidosis, a condition where abnormal proteins accumulate in organs, causing damage. Researchers aim to assess the drug's safety and its impact on disease activity by experimenting with different doses. The trial consists of two parts: the first part identifies the best doses, and the second part evaluates safety using those doses. This trial may suit adults with AL amyloidosis who have relapsed or not responded to previous treatments. Participants must visit a hospital or clinic regularly for up to two years. As a Phase 1, Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications for the ABBV-383 trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the investigational drug ABBV-383, also known as Etentamig, is being tested for safety in humans. Early results indicate that ABBV-383 is a bispecific antibody, meaning it can interact with two different targets in the body: CD3 on T-cells (a type of immune cell) and BCMA on certain cancer cells.

Ongoing studies are examining its use in treating multiple myeloma, a type of blood cancer. These studies are important for gathering safety information about the drug's effects on humans. Although detailed safety data for AL amyloidosis is not yet available, these studies are crucial for understanding how well people tolerate the treatment and what side effects might occur.

Since ABBV-383 is in the early stages of clinical testing, researchers are still working to determine its safety and effectiveness. This phase is essential for identifying any adverse effects and ensuring the treatment is safe for humans. Participating in a clinical trial involves regular check-ups and monitoring to ensure participant safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about ABBV-383 (etentamig) for amyloidosis because it targets the disease differently than standard treatments. Most current treatments focus on reducing amyloid production or stabilizing existing amyloid deposits. However, ABBV-383 is designed to directly target and remove amyloid fibrils, potentially offering a more effective way to clear the harmful protein build-up. This novel mechanism could lead to significant improvements in managing amyloidosis, providing hope for better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for AL amyloidosis?

Research has shown that ABBV-383, also known as Etentamig, could be helpful in treating AL amyloidosis. Studies have identified ABBV-383 as a special type of antibody that targets two proteins: BCMA, found on certain cells, and CD3, found on T-cells. This targeting helps the immune system attack the harmful cells causing the disease. Early results from ongoing studies suggest that ABBV-383 can effectively help the immune system fight AL amyloidosis, with promising results in reducing disease activity. These findings offer hope that ABBV-383 might be an effective treatment option for people with this condition. Participants in this trial will receive different doses of ABBV-383 to evaluate its safety and effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for adults with AL amyloidosis, a condition where abnormal proteins build up in organs. Participants must have had prior treatments including proteasome inhibitors and anti-CD38 antibodies, be moderately healthy (ECOG <=2), and have measurable disease impact on at least one organ.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I have been treated with drugs targeting proteins and CD38 before.

I have been diagnosed with AL amyloidosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive one of three doses of ABBV-383 to determine the doses for the next phase

Up to 2 years

Regular visits at a hospital or clinic

Safety Expansion

Participants receive one of two doses determined during the dose escalation phase

Up to 2 years

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-383

Trial Overview The study tests ABBV-383, an experimental drug for AL amyloidosis. It has two parts: first to find the right dose and second to assess safety at selected doses. Patients receive the drug through IV over approximately two years across various global sites.

How Is the Trial Designed?

Group I: Safety Expansion: ABBV-383 (etentamig) Expansion B Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) expansion dose B during the approximately 2 year study duration.

Group II: Safety Expansion: ABBV-383 (etentamig) Expansion A Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) expansion dose A during the approximately 2 year study duration.

Group III: Dose Escalation: ABBV-383 (etentamig) Dose C Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) dose C during the approximately 2 year study duration.

Group IV: Dose Escalation: ABBV-383 (etentamig) Dose B Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) dose B during the approximately 2 year study duration.

Group V: Dose Escalation: ABBV-383 (etentamig) Dose A Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) dose A during the approximately 2 year study duration.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

The fully human bispecific antibody REGN5458, which targets B-cell maturation antigen (BCMA) and CD3, effectively induces T-cell killing of multiple myeloma cells and shows strong antitumor activity in mouse models, demonstrating its potential as a rapid therapeutic option.

In head-to-head comparisons, REGN5458 cleared tumors more quickly than anti-BCMA CAR T cells, suggesting that bispecific antibodies can engage existing T cells at the tumor site for immediate action, while CAR T cells require time to activate and expand before they can attack the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. DiLillo, DJ., Olson, K., Mohrs, K., et al.[2021]

A study compared the efficacy of a CD3 bispecific antibody and two types of antibody-drug conjugates (ADCs) targeting B-cell maturation antigen (BCMA) in treating myeloma, showing that both modalities effectively killed myeloma cells in vitro and in vivo.

The CD3 bispecific antibody demonstrated superior potency and consistency in killing primary patient cells compared to ADCs, leading to its advancement into phase I clinical trials due to its better efficacy and improved toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma. Panowski, SH., Kuo, TC., Zhang, Y., et al.[2020]

The study developed several bispecific BCMA-CD3 antibodies that effectively target and kill multiple myeloma cells, demonstrating specific binding and cytotoxic activity in vitro with a strong affinity in the nanomolar range.

In vivo testing in a mouse model showed that these BCMA bispecific antibodies had high efficacy against multiple myeloma, supporting their potential for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. Wu, L., Huang, Y., Sienkiewicz, J., et al.[2022]

ABBV-383, a bispecific antibody targeting B-cell maturation antigen and CD3, showed a promising overall response rate (ORR) of 68% in patients with relapsed/refractory multiple myeloma (RRMM) at doses of 40 mg or higher, indicating its potential efficacy as a treatment option.

The treatment was generally well tolerated, with common side effects including neutropenia (37%) and cytokine release syndrome (57%), and no deaths were deemed related to the study drug, suggesting a favorable safety profile for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. D'Souza, A., Shah, N., Rodriguez, C., et al.[2023]

BCMA-targeting bispecific antibodies, like teclistamab, show significant effectiveness in treating heavily pretreated multiple myeloma patients, utilizing mechanisms such as T-cell redirection to eliminate cancer cells.

Cytokine release syndrome is the most common side effect of these treatments, but it can be effectively managed with medications like tocilizumab or steroids, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma. Verkleij, CPM., Frerichs, KA., Broekmans, M., et al.[2020]

In a phase 3 trial involving 260 newly diagnosed patients with AL amyloidosis, birtamimab did not show a significant improvement in overall survival or hospitalization rates compared to placebo, leading to the trial's early termination due to futility.

However, a post hoc analysis revealed that patients with Mayo stage IV AL amyloidosis treated with birtamimab had a significant survival advantage at 9 months, with 74% survival compared to 49% in the placebo group, suggesting potential efficacy in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Birtamimab plus standard of care in light-chain amyloidosis: the phase 3 randomized placebo-controlled VITAL trial. Gertz, MA., Cohen, AD., Comenzo, RL., et al.[2023]

TNB-383B effectively induces the killing of plasma cells in bone marrow from patients with relapsed multiple myeloma, showing dose-dependent lysis starting at very low doses (0.001 μg).

The treatment leads to significant degranulation of cytotoxic T lymphocytes (CTLs) and modulates cytokine responses, with notable increases in IL-2/TNFα and IP10, indicating a robust immune response without significant T cell expansion or severe cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. Foureau, DM., Bhutani, M., Robinson, M., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36029527/

A Phase I First-in-Human Study of ABBV-383, a B-Cell ... ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study.

2. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/etentamig

Definition of anti-BCMA/anti-CD3 T-cell engaging bispecific ... Upon administration, anti-BCMA/anti-CD3 T-cell engaging bispecific antibody ABBV-383 binds to both CD3 on cytotoxic T lymphocytes (CTLs) and BCMA found on BCMA- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03933735

NCT03933735 | A Study of TNB-383B in Participants With ... This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-383B, a BCMA x CD3 T-cell engaging bispecific ...

4. news.abbvie.com news.abbvie.com/2024-06-05-AbbVie-Advances-Oncology-Pipeline-With-Start-of-Multiple-Myeloma-Phase-3-Clinical-Trial-for-Investigational-Asset-ABBV-383

AbbVie Advances Oncology Pipeline With Start of Multiple ... ABBV-383 is a distinctive B-cell maturation antigen (BCMA) and CD3 bispecific antibody T-cell engager composed of bivalent BCMA-binding domains ...

5. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=TNB383B.0001

A Study of TNB-383B in Participants With Relapsed or ... This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-383B, a BCMA x CD3 T-cell engaging bispecific ...