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A Study of Mavorixafor in Participants With Severe Congenital Neutropenia and Chronic Neutropenia Disorders

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ClinicalTrials.gov Identifier: NCT04154488
Recruitment Status : Recruiting
First Posted : November 6, 2019
Last Update Posted : July 30, 2021
Sponsor:
Information provided by (Responsible Party):
X4 Pharmaceuticals

Brief Summary:
This Phase 1b study will determine the safety and tolerability of mavorixafor in participants with severe chronic idiopathic neutropenia (CIN) and selected congenital neutropenia disorders. The anticipated enrollment is up to 45 participants.

Condition or disease Intervention/treatment Phase
Neutropenia Drug: Mavorixafor Phase 1

Detailed Description:
Following the 28 day screening period, participants will return to the clinic for their interim visits up to Day 45 or end of study visit. Visits occurring between screening and the Day 45 or end of study visit may be conducted as at-home study visits at the discretion of the Investigator. The total time on study for each participant is approximately 6 weeks.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1B, Open-Label, Multicenter Study of Mavorixafor in Patients With Severe Congenital Neutropenia and Chronic Neutropenia Disorders
Actual Study Start Date : October 16, 2020
Estimated Primary Completion Date : October 15, 2021
Estimated Study Completion Date : December 15, 2021


Arm Intervention/treatment
Experimental: Mavorixafor
Adult participants and adolescent participants who weigh more than 50 kilograms (kg) will receive mavorixafor 400 milligrams (mg) (4 capsules of 100 mg each) orally once daily (QD) in the morning for 14 days. Adolescents weighing less than or equal to 50 kg will receive mavorixafor 200 mg (2 capsules of 100 mg each) QD in the morning for 14 days.
Drug: Mavorixafor
Mavorixafor capsules will be administered per dose and schedule specified in the arm.
Other Name: X4P-001




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline (Day -1) up to end of study (Day 44) ]

Secondary Outcome Measures :
  1. Absolute Neutrophil Count (ANC) of Mavorixafor in Participants With Severe CIN in Combination With Steady-State Granulocyte-Colony Stimulating Factor (G-CSF) [ Time Frame: Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, and 6 hours (each ± 15 minutes) post-dose at Day 1, 8, and 14 ]
  2. Area Under the Curve for ANC (AUCANC) of Mavorixafor in Participants With Severe CIN in Combination With Steady-State G-CSF [ Time Frame: Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, and 6 hours (each ± 15 minutes) post-dose at Day 1, 8, and 14 ]
  3. Serum Concentration of Mavorixafor in Relation to ANC and AUCANC in Participants With Severe CIN [ Time Frame: Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, and 6 hours (each ± 15 minutes) post-dose at Day 1, 8, and 14 ]


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For all participants:

    • Sign the informed consent form (ICF) and be willing and able to comply with the protocol.
    • Weigh ≥15 kg
    • Agree to use contraception as follows:

      i) For women of childbearing potential (WOCBP): agree to use highly effective contraceptive methods from screening through the study and for at least 4 weeks after the last dose of study drug.

ii) For male participants: agree to use a condom with any WOCBP sexual partner from screening through the study and for at least 4 weeks after the last dose of study drug.

  • Participants with severe chronic idiopathic neutropenia (CIN):

    • Have a history of ANC ≤500 cells/microliter (μL), lasting for more than 3 months at any time since diagnosis.
    • Have been diagnosed with severe CIN more than 12 months ago that is not attributable to medications, infectious, genetic, inflammatory, autoimmune, or malignant causes.
    • Be currently treated with a steady-state G-CSF regimen for greater than (>) 15 days before receiving the first dose of study drug.
    • Have cytogenetics that do not suggest clonal evolution on the most recent bone marrow biopsy/aspirate, if performed.
    • Have no history of associated thrombocytopenia (platelets < 75,000/uL) nor anemia <10.0 g/dL before G-CSF therapy initiation.
    • Not have neutropenia secondary to another pathology, such as a systemic autoimmune disorder and in particular rheumatological or hematological.
  • Participants with selected congenital neutropenia conditions including GSD1b (GSD1b; SLC37A4), G6PC3 deficiency (G6PC3), or GATA2 deficiency (GATA2):

    • May be currently receiving steady-state G-CSF dosing or not have been on G-CSF for >15 days.
    • Must have documentation of the mutational status before enrolling in the study.

Exclusion Criteria:

  • Known systemic hypersensitivity to the mavorixafor drug substance or its inactive ingredients.
  • Diagnosis of cyclical neutropenia.
  • Is pregnant or nursing.
  • Known history of a positive serology or viral load for human immunodeficiency virus (HIV) or a known history of acquired immune deficiency syndrome.
  • At screening, has laboratory test results meeting one or more of the following criteria:

    • Positive hepatitis C virus (HCV) antibodies with confirmation by HCV-ribonucleic acid polymerase chain reaction reflex testing.
    • Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb).

Note: If a participant tests negative for HBsAg but positive for HBcAb, the participant would be considered eligible if the participant tests positive for antibody to HBsAg reflex testing.

  • At screening, has laboratory test results meeting one or more of the following criteria:

    • Hemoglobin <10.0 grams/deciliter (g/dL)
    • Platelet count <75,000/μL
    • Mild/moderate renal impairment 30 to 60 glomerular filtration rate
    • Serum aspartate transaminase >2.5 * upper limit of normal (ULN)
    • Serum alanine transaminase >2.5 * ULN
    • Total bilirubin >1.5 * ULN (unless due to Gilbert's syndrome, in which case total bilirubin greater than or equal to (≥) 3.0 * ULN and direct bilirubin >1.5 * ULN)
  • Within 2 weeks before Day 1, received any of the following treatments:

    • Glucocorticoids (>5 mg prednisone equivalent per day)
    • Medication prohibited based on cytochrome P450 (CYP) and/or P-glycoprotein (P-gp) interaction.
  • At the planned initiation of study drug, has an uncontrolled infection requiring chronic or prophylactic use of antibiotics (systemic or inhaled) within 4 weeks before Day 1.
  • Has any other medical or personal condition that, in the opinion of the Investigator, may potentially compromise the safety or compliance of the participant, or may preclude the participant's successful completion of the clinical study.
  • Inability to ingest study drug as presented.
  • Has a history of any hematologic malignancy.
  • Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); any history of arrhythmia will be discussed with the sponsor's medical monitor before participant's entry into the study.
  • Prolonged corrected QT interval (QTc) using Fridericia's formula (QTcF) on pre-entry electrocardiogram (ECG) (≥450 milliseconds [ms]).
  • Has an associated diagnosis of rheumatoid arthritis, systemic lupus erythematosus, or inflammatory bowel disease (IBD).

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): NCT04154488


Contacts
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Contact: Patient Affairs and Advocacy 857-529-5779 patientinfo@x4pharma.com
Contact: Patient Affairs and Advocacy patientinfo@x4pharma.com

Locations
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United States, Iowa
University of Iowa Hospital and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Anjali Sharathkumar         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Kelly Jo Walkovich         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: David Wilson         
United States, New York
Northwell Feinstein Institutes for Medical Research Not yet recruiting
Manhasset, New York, United States, 11030
Contact: Adrianna Vlachos         
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Seth Corey         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: David C. Dale         
Sponsors and Collaborators
X4 Pharmaceuticals
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Responsible Party: X4 Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04154488    
Other Study ID Numbers: X4P-001-104
First Posted: November 6, 2019    Key Record Dates
Last Update Posted: July 30, 2021
Last Verified: July 2021

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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 X4 Pharmaceuticals:
Chronic congenital neutropenia
Chronic idiopathic neutropenia
SCN
CIN
CXCR4
Mavorixafor
Neutropenia glycogen storage disease type 1b
GSD1b
G6PC3
SLC37A4
GATA2
Additional relevant MeSH terms:
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Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases