What side effects are associated with this type of intervention?

Common treatments for amyloidosis, including chemotherapy and immunotherapy, often have side effects such as nausea, fatigue, and increased risk of infections due to immunosuppression. Specific agents like those in the ZN-d5 trial may also cause more targeted side effects, such as amyloid-related imaging abnormalities (ARIAs), which can include edema and cerebral hemorrhage. Serious adverse events, although less common, can occur and may include organ toxicity or severe allergic reactions.

What prior FDA approvals exist?

FDA-approved treatments for amyloidosis include several drugs targeting different mechanisms. For AL amyloidosis, treatments like bortezomib, lenalidomide, and daratumumab have been approved, focusing on reducing the production of amyloidogenic light chains. Bortezomib is a proteasome inhibitor, lenalidomide is an immunomodulatory drug, and daratumumab is an anti-CD38 monoclonal antibody. For ATTR amyloidosis, patisiran and inotersen, which are RNA-targeted therapies that reduce hepatic transthyretin (TTR) synthesis, have been approved. These treatments aim to reduce the availability of misfolded proteins that form amyloid deposits. While the specific mechanism of ZN-d5 is not detailed, it is likely being studied in the context of these existing therapeutic strategies.

What other types of research exist?

Promising alternatives to ZN-d5 for Amyloidosis patients in 2024 include recombinant ADAMTS-13 (BAX 930; SHP655), which has shown safety and tolerability in phase 1 trials for congenital thrombotic thrombocytopenic purpura, and cyclic peptide inhibitors like ZD7349, which have demonstrated efficacy in cell adhesion and arthritis models. These alternatives are in advanced stages of development and have shown potential in related conditions.

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ZN-d5 for AL Amyloidosis

Phase 1 & 2

Waitlist Available

Research Sponsored by K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adequate bone marrow function prior to first administration of study drug

Assessment of t(11,14) status by FISH

Must not have

Presence of non-AL amyloidosis, including wild-type or mutated ATTR amyloidosis

Prior treatment with other BCL-2 inhibitors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 48 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called ZN-d5 for patients with Light Chain (AL) Amyloidosis whose condition has come back or did not respond to other treatments. The drug aims to reduce harmful protein production in the body.

Who is the study for?

This trial is for adults with AL Amyloidosis who have tried treatments before but are still sick. They should be fairly active (able to care for themselves), have decent bone marrow function, and no heart failure or serious arrhythmias. People can't join if they've had more than three prior therapies, other types of amyloidosis like ATTR, or a diagnosis of multiple myeloma.

What is being tested?

The study tests ZN-d5 on its own in people whose AL Amyloidosis has come back or didn't respond to treatment. It's an early-stage trial (Phase 1/2) where everyone gets the same experimental drug to see how safe it is and if it works against this disease.

What are the potential side effects?

Since ZN-d5 is new and being tested, side effects aren't fully known yet. However, similar drugs often cause nausea, fatigue, low blood counts that can lead to infections or bleeding problems, and sometimes liver issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My bone marrow is functioning well enough for treatment.

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My cancer has been tested for the t(11,14) genetic change.

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

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I have been diagnosed with AL amyloidosis through tissue testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My condition is non-AL amyloidosis, including wild-type or mutated ATTR.

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I have been treated with BCL-2 inhibitors before.

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My condition is classified as Stage IV according to Mayo 2012.

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I have been diagnosed with multiple myeloma.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 48 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~48 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 48 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose limiting toxicities

Safety and Tolerability

Secondary study objectives

Assess the hematologic response to ZN-d5

Duration and time to hematologic response to ZN-d5

PK Parameter: Finding half-life of ZN-d5

+3 more

Other study objectives

Zinc

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment ArmExperimental Treatment1 Intervention

Subjects will receive ZN-d5 orally (PO), once (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ZN-d5

2021

Completed Phase 2

~80

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for amyloidosis target the reduction of amyloid protein production and deposition. RNA silencing techniques, such as siRNA and ASOs, decrease the levels of precursor proteins, thereby reducing amyloid deposits. Gene editing, like CRISPR-Cas9, aims to knock out genes responsible for amyloidogenic proteins. Inhibition of proteolysis prevents the formation of amyloid fibrils by blocking the cleavage of precursor proteins. Monoclonal antibodies, such as daratumumab, target specific amyloid proteins to enhance their clearance. These mechanisms are vital for amyloidosis patients as they directly address the root cause of amyloid buildup, potentially improving organ function and patient outcomes.

A critical analysis of postulated pathogenetic mechanisms in amyloidogenesis.A clinico-epidemiological study of macular amyloidosis from north India.Diagnosis and immunohistochemical classification of systemic amyloidoses. Report of 43 cases in an unselected autopsy series.