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Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis

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ClinicalTrials.gov Identifier: NCT05199337
Recruitment Status : Recruiting
First Posted : January 20, 2022
Last Update Posted : January 20, 2022
Sponsor:
Information provided by (Responsible Party):
K-Group Alpha, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Amyloidosis AL Amyloidosis Drug: ZN-d5 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 30, 2021
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis

Arm Intervention/treatment
Experimental: Treatment Arm
Subjects will receive ZN-d5 orally (PO), once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: ZN-d5
ZN-d5 will be administered orally
Other Name: Study Drug




Primary Outcome Measures :
  1. 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

  2. Dose limiting toxicities [ Time Frame: 18 Months ]
    Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects


Secondary Outcome Measures :
  1. PK Parameter: Finding max concentration (Cmax) of ZN-d5 [ Time Frame: 48 months ]
    Determine the maximum observed concentration (Cmax) of ZN-d5 collected in the plasma from subjects at different dose levels.

  2. PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5 [ Time Frame: 48 months ]
    Determine the time it takes for ZN-d5 to reach the maximum concentration (or Cmax) at different dose levels of ZN-d5

  3. PK Parameter: Finding half-life of ZN-d5 [ Time Frame: 48 months ]
    Finding Half-life (t1/2) of ZN-d5 in subjects at different doses the time it takes for half the drug concentration to be eliminated

  4. PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5 [ Time Frame: 48 months ]
    Determine the total exposure (AUC) of ZN-d5 experienced by the subject at different dose levels


Other Outcome Measures:
  1. To assess potential biomarkers of ZN-d5 [ Time Frame: 48 months ]
    Peripheral B-Cell Counts



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of AL amyloidosis based on histopathology, the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid.
  2. Prior AL amyloidosis treatment and has received at least one, but no more than three lines of prior therapy ;
  3. Measurable disease defined by serum differential free light chain;
  4. Bone marrow plasma cells <30%;
  5. Assessment of t(11,14) status by FISH;
  6. Eastern Cooperative Oncology Group performance <2 ;
  7. History of organ involvement (current measurable organ disease is not required for enrollment): Renal, Cardiac, Hepatic, Gastrointestinal, and Neurologic;
  8. Adequate bone marrow function prior to first administration of study drug;
  9. Adequate organ function;

    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN;
    • Alkaline phosphatase ≤5 x ULN;
    • Total bilirubin ≤1.5 x ULN except for subjects with Gilbert syndrome;
    • Estimated glomerular filtration rate (CKD-EPI) ≥45 mL/min/1.73 m2;
  10. Female subjects of childbearing potential must have a negative serum pregnancy test and agree to use contraception while on study.

Exclusion Criteria:

  1. Presence of non-AL amyloidosis, including wild type or mutated ATTR amyloidosis.;
  2. Diagnosis of multiple myeloma;
  3. Mayo2012 Stage IV disease: NT-ProBNP ≥ 1800 ng/L, cTnT ≥ 0.025 ng/mL (0.025 µg/L), and dFLC ≥ 180 mg/L;
  4. Cardiac conditions including:

    • New York Heart Association (NYHA) Class III or IV heart failure;
    • History of sustained ventricular tachycardia or fibrillation, or ventricular arrhythmias
    • QTc >500 msec;
    • Atrial fibrillation with inadequate anti-coagulation;
    • Second- or third-degree atrioventricular block (Mobitz type I is permitted);
    • History of myocardial infarction, coronary stent placement, or coronary artery bypass grafting;
    • Left ventricular ejection fraction (LVEF) by echocardiogram <35%;
    • Supine systolic blood pressure <90 mm Hg or symptomatic orthostatic hypotension (decrease in systolic blood pressure upon standing of >20 mm Hg;
  5. Positive serology for human immunodeficiency virus, hepatitis B, or hepatitis C unless no detectable hepatitis C viral load;
  6. Concurrent treatment with drugs that prolong the QT interval, are strong CYP3A inhibitors or strong or moderate CYP3A inducers, or are P-glycoprotein inhibitors;
  7. Concurrent treatment with agents used to treat plasma cell disorders or AL amyloidosis, including experimental agents;
  8. Prior treatment with venetoclax or other BCL-2 inhibitors;
  9. Other active systemic malignancy or other severe, unstable, or poorly controlled acute, chronic medical conditions or active and uncontrolled clinically significant infection;
  10. Females who are pregnant or intending to become pregnant, or who are breastfeeding or intending to breastfeed, during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05199337


Contacts
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Contact: Anthony Fiorino, MD, PhD 8582634333 info@zenopharma.com

Locations
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United States, Colorado
Site 0198 Not yet recruiting
Denver, Colorado, United States, 80218
United States, Tennessee
Site 0199 Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
K-Group Alpha, Inc.
Investigators
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Study Director: Anthony Fiorino, MD, PhD K-Group Alpha, Inc.
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Responsible Party: K-Group Alpha, Inc.
ClinicalTrials.gov Identifier: NCT05199337    
Other Study ID Numbers: ZN-d5-003
First Posted: January 20, 2022    Key Record Dates
Last Update Posted: January 20, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by K-Group Alpha, Inc.:
Amyloidosis
AL Amyloidosis
RRAL
BCL2 Inhibitor
t(11;14)
ZN-d5
Light Chain Amyloidosis
Light chain (AL) Amyloidosis
Additional relevant MeSH terms:
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Immunoglobulin Light-chain Amyloidosis
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Paraproteinemias