AmyloidosisPhase 1/2NCT05199337
Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis
A Phase 1/2 study testing ZN-d5 in people with Amyloidosis and AL Amyloidosis, run by K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. at 21 sites in 7 countries.
Trial summary
This is a single arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyloidosis, AL Amyloidosis
- What is being tested?
- ZN-d5
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 21 sitesin 7 countries
- Study dates
- 30 Nov 2021to 14 Feb 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of AL amyloidosis based on histopathology, the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid.
- Prior AL amyloidosis treatment and has received at least one, but no more than three lines of prior therapy;
- At least 3 months from hematopoietic stem cell transplantation or the shorter of 60 days or 5 half-lives for biologics, small molecules, or investigational drugs prior to starting treatment;
- Measurable disease defined by serum differential free light chain;
- Assessment of t(11,14) status by FISH;
- Eastern Cooperative Oncology Group performance status ≤2 ;
Show all 9Show fewer
- History of organ involvement
- Adequate bone marrow function prior to first administration of study drug;
- Adequate organ function;
Who cannot join
- Presence of non-AL amyloidosis, including wild-type or mutated ATTR amyloidosis;
- Diagnosis of multiple myeloma according to the 2014 International Myeloma Working Group diagnostic criteria;
- Mayo 2012 Stage IV disease;
- Cardiac involvement exclusions apply to some subjects, including heart failure and cardiac arrhythmias.
- Prior treatment with other BCL-2 inhibitors;
Trial locations and contacts
21 sites in 7 countries.
21 sites in 7 countries
United States5 sites
Colorado Blood Cancer Institute
Denver, Colorado, 80218
University of Southern California
Los Angeles, California, 90089
Tennessee Oncology
Nashville, Tennessee, 37203
Tulane University
New Orleans, Louisiana, 70112
Washington University
St Louis, Missouri, 63130
Australia4 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Princess Alexandra Hospital
Brisbane, Queensland, 4102
Sir Charles Gairdner Hospital
Nedlands, Western Australia
Blackwater (Westmead) Hospital
Westmead, New South Wales, 2145
Israel4 sites
Rambam Hospital
Haifa, 3109601
Hadassah Medical Center
Jerusalem
Sheba Medical Center
Tel Aviv
Tel Aviv Sourasky Medical Center PPDS
Tel Aviv
Spain4 sites
ICO Badalona-H.U. Germans Trias i Pujol
Barcelona, Badalona
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Clínico Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120
Clinico de Salamanca
Salamanca
Italy2 sites
IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi
Bologna
Fondazione I.R.C.C.S. Policlinico San Matteo
Pavia
About this study
Official title: A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis
This is a single arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis.
Read the detailed description
A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis. The first part of the study is phase 1 dose-escalation and the second part will be phase 2.
- Conditions
- Amyloidosis, AL Amyloidosis
- Being tested
- ZN-d5
- Keywords
- Amyloidosis, AL Amyloidosis, RRAL, BCL2 Inhibitor, t(11;14), ZN-d5, Light Chain Amyloidosis, Light chain (AL) Amyloidosis
- Medical subject headings
- Amyloidosis, Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZN-d5Drug
Also called Study Drug
ZN-d5 will be administered orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | 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. Receives: Drug: ZN-d5 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Measured: 18 Months
Dose limiting toxicities
Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects
Measured: 18 Months
Secondary outcomes (6)
PK Parameter: Finding max concentration (Cmax) of ZN-d5
Determine the maximum observed concentration (Cmax) of ZN-d5 collected in the plasma from subjects at different dose levels.
Measured: 48 months
PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5
The duration (in hours) it takes for ZN-d5 to reach the maximum concentration (or Cmax) collected in the plasma from subjects at different dose levels.
Measured: 48 months
PK Parameter: Finding half-life of ZN-d5
The time takes for half the drug concentration of ZN-d5 to be eliminated (Half-life) from the plasma that was collected from subjects at different dose levels
Measured: 48 months
PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5
The total exposure of ZN-d5 over time (AUC) from the plasma collected by the subject at different dose levels.
Measured: 48 months
Assess the hematologic response to ZN-d5
The number of Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR), Progressive Disease (PD) using the AL Amyloidosis Hematologic Response Criteria.
Measured: 48 months
Duration and time to hematologic response to ZN-d5
The rate of, duration of, and time to CR, modified Complete Response (mCR), CR+VGPR, and mCR+VGPR
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2022
- Study start30 Nov 2021
- Primary completion14 Feb 2024
- Study completion14 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Affairs, Study director, K-Group Alpha subsidiary of Zentalis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05199337
- Sponsor's protocol ID
- ZN-d5-003
- Status last verified
- Sep 2024
- First submitted
- 9 Jan 2022
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Locke M, Nieto M. AL Amyloidosis: Current Treatment and Outcomes. Adv Hematol. 2025 Mar 3;2025:7280805. doi: 10.1155/ah/7280805. eCollection 2025.
PubMed 40226119
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis
- ClinicalTrials.gov ID
- NCT05199337
- Acronym / sponsor ID
- ZN-d5-003
- Conditions
- Amyloidosis, AL Amyloidosis
- Keywords
- Amyloidosis, AL Amyloidosis, RRAL, BCL2 Inhibitor, t(11;14), ZN-d5, Light Chain Amyloidosis, Light chain (AL) Amyloidosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 14 Feb 2024 (actual)
- Study completion
- 14 Feb 2024 (actual)
- First posted
- 20 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis.
Detailed description
A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis. The first part of the study is phase 1 dose-escalation and the second part will be phase 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: ZN-d5Subjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis of AL amyloidosis based on histopathology, the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid.
- Prior AL amyloidosis treatment and has received at least one, but no more than three lines of prior therapy;
- At least 3 months from hematopoietic stem cell transplantation or the shorter of 60 days or 5 half-lives for biologics, small molecules, or investigational drugs prior to starting treatment;
- Measurable disease defined by serum differential free light chain;
- Assessment of t(11,14) status by FISH;
Key exclusion criteria (5 listed)
- Presence of non-AL amyloidosis, including wild-type or mutated ATTR amyloidosis;
- Diagnosis of multiple myeloma according to the 2014 International Myeloma Working Group diagnostic criteria;
- Mayo 2012 Stage IV disease;
- Cardiac involvement exclusions apply to some subjects, including heart failure and cardiac arrhythmias.
- Prior treatment with other BCL-2 inhibitors;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZN-d5Also: Study DrugZN-d5 will be administered orally | Drug | Treatment Arm |
Primary outcome
Safety and Tolerability
Time frame: 18 Months
Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Dose limiting toxicities
Time frame: 18 Months
Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects
6 secondary outcomes
PK Parameter: Finding max concentration (Cmax) of ZN-d5
Time frame: 48 months
PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5
Time frame: 48 months
PK Parameter: Finding half-life of ZN-d5
Time frame: 48 months
PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5
Time frame: 48 months
Assess the hematologic response to ZN-d5
Time frame: 48 months
Duration and time to hematologic response to ZN-d5
Time frame: 48 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 40226119Locke M, Nieto M. AL Amyloidosis: Current Treatment and Outcomes. Adv Hematol. 2025 Mar 3;2025:7280805. doi: 10.1155/ah/7280805. eCollection 2025.
- Individual participant dataSharing planned: No
Related trials for Amyloidosis
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
Active, not recruitingPhase 2
A Study to Evaluate the Safety and Biomarker Effects of RO7269162 in Participants at Risk for or at the Prodromal Stage of Alzheimer's Disease (AD)
Alzheimer's Disease
Active, not recruitingObservational study
A Retrospective Observational Study of Epidemiology and Outcomes in Transthyretin Amyloid Cardiomyopathy in Germany
ATTR-CM (Transthyretin Amyloid Cardiomyopathy)
Active, not recruitingPhase 3
EPIC-ATTR: A Study to Evaluate the Effect of Eplontersen on the Transthyretin Reduction and Long-term Safety in Chinese Subjects With Transthyretin Amyloid Cardiomyopathy
Transthyretin Amyloid Cardiomyopathy
RecruitingObservational study
PET Imaging in the Baltimore Longitudinal Study of Aging (BLSA)
Aging
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Affairs study director
K-Group Alpha subsidiary of Zentalis Pharmaceuticals
21 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ZN-d5 in people with Amyloidosis and AL Amyloidosis, run by K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. at 21 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Australia, Israel, Spain, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability (time frame: 18 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05199337, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.