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

X4 Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Neutropenia

Treatments: Drug: Mavorixafor

Study type: Interventional

Funder types: Industry

Identifiers

NCT04154488

X4P-001-104

Details and patient eligibility

About

This is a 2-part study of mavorixafor in participants diagnosed with chronic neutropenia. The main goal of Part 1 (Phase 1b) is to help researchers learn more about how the investigational medicine, mavorixafor, impacts people living with chronic neutropenia (including congenital, idiopathic, and cyclic). In Part 2 (Phase 2), the safety and tolerability of chronic dosing of mavorixafor will be evaluated in a larger participant population and the impact of 6-month chronic dosing of mavorixafor on participant neutropenia.

Full description

Part 1: Participants will receive one oral dose of mavorixafor and be monitored for 8 hours to see if neutrophil cell counts increase. Participants screened after implementation of Protocol Version 8.0, do not need to enter Part 1 and can start with the Part 2 Screening visit (Day -28 to Day -1).

Part 2: For participants enrolled in the study before implementation of Protocol Version 8.0, Part 2 will include those who completed Part 1 and exhibited a response to treatment. Eligible participants from Part 1 enrolled in the study before implementation of Protocol Version 8.0, can directly roll-over to the Baseline (Day -3 to Day -1) visit in Part 2. Participants will receive once daily oral dosing of mavorixafor for 6 months and be monitored throughout to see if neutrophil cell counts increase.

Study visits can be conducted at-home or at one of many study clinic locations, depending on the participant's preference.

Enrollment: 32 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

For all participants (Parts 1 and 2):

• Sign the informed consent form (ICF) and be willing and able to comply with the protocol.

• Weigh ≥15 kg

• Agree to use a highly effective form of contraception if sexually active.

• Participants may be eligible for the study whether they are on or off granulocyte-colony stimulating factor (G-CSF) treatment.

  • Note: Participants who are on G-CSF must be on a stable dose for ≥14 days prior to the Baseline visit and should not have an ANC ≥10,000 cells/μL.
  • Note: Participants who are not on G-CSF must be off for ≥14 days prior to the Baseline visit and have an ANC ≤1000 cells/µL at the Screening visit.
  • Note: Participants with Shwachman-Diamond syndrome, Cohensyndrome, and warts, hypogammaglobulinemia, infections and myelokathexis syndrome are eligible. Other types of chronic neutropenic disorders may also be eligible for enrollment upon discussion and approval with Sponsor and Study Medical Monitor.

• Have been diagnosed with chronic neutropenia for ≥6 months prior to the Screening visit that is not attributable to medications, active or recent (≤3 months) infections, or malignant cause.

Part 2 only:

• Participants enrolled in the study before implementation of Protocol Version 8.0 must have completed Part 1 and exhibited a positive response to treatment.
• Participant has a history of symptomatic chronic neutropenia confirmed by the Investigator.

Key Exclusion Criteria (Parts 1 and 2):

• Known systemic hypersensitivity to the mavorixafor drug substance or its inactive ingredients.

• Is pregnant, breastfeeding, or plans to become pregnant over the next 8 months.

• Known history of a positive serology or viral load for human immunodeficiency virus (HIV) or a known history of acquired immune deficiency syndrome.

• Known active SARS-CoV-2 virus (COVID-19) infection or a positive test within the local accepted clinical and governmental guidelines for a communicable window.

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

  • Hemoglobin <9.0 grams/deciliter (g/dL)
  • Platelets <30,000/μL
  • Estimated glomerular filtration rate (eGFR) ≤60 mL/minute/1.73 meter (m)^2, as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
  • Serum aspartate transaminase >2.5 x upper limit of normal (ULN)
  • Serum alanine transaminase >2.5 x ULN
  • Total bilirubin >1.5 x ULN (unless due to Gilbert's syndrome, in which case total bilirubin greater than or equal to (≥) 3.0 x ULN and direct bilirubin >1.5 x ULN)

• ≤14 days before Day 1, received any of the following treatments:

  • Systemic glucocorticoids (>5 mg prednisone equivalent per day).
  • Medication prohibited based on cytochrome P450 (CYP)2D6 potential for interaction.

• Is taking a medication which is a strong inhibitor of CYP3A4, unless the Investigator and Medical Monitor conclude that the medication must be used during the study and is permissible with modification of mavorixafor dose.

• Has an infection requiring use of systemic antibiotics ≤4 weeks before the Baseline visit.

• Has a medical or personal condition that may potentially compromise the safety or compliance of the participant, or may preclude the participant's successful completion of the clinical study or that in the opinion of the Investigator or the Sponsor could interfere with the objectives of the study.

• Has had major surgery ≤4 weeks before the Baseline visit.

• Inability to ingest mavorixafor capsules.

• Has an active malignancy or history of (≤5 years prior to enrollment) in the study of solid, metastatic, or hematologic malignancy. Exception: basal cell carcinoma in situ of the skin that has been adequately treated.

• Diagnosed or has 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 using Fridericia's formula at the Screening visit electrocardiogram (ECG) (>450 milliseconds [ms])

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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32 participants in 1 patient group

Mavorixafor

Experimental group

Description:

Part 1: 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 on Day 1. Adolescents weighing less than or equal to 50 kg will receive mavorixafor 200 mg (2 capsules of 100 mg each), orally once on Day 1. Part 2: Eligible participants from Part 1 will receive once daily dosing of mavorixafor for 6 months.

Treatment:

Drug: Mavorixafor