A Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections

Phase 3

Recruiting

• Conditions: Neutropenia
• Interventions: Drug: Mavorixafor; Drug: Placebo

• Registration Number: NCT06056297
• Lead Sponsor: X4 Pharmaceuticals

Brief Summary

The purpose of this study is to demonstrate the efficacy and evaluate the safety, and tolerability of mavorixafor in participants with congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorders who are experiencing recurrent and/or serious infections as assessed by demonstrating its clinical benefit and increasing levels of circulating neutrophils.

Detailed Description

All participants will continue their pre-study background therapy, defined as the participant's current treatment regimen. Options include, but are not limited to granulocyte-colony stimulating factor (G-CSF), immunoglobulin replacement therapy, prophylactic antibiotics, or "watchful waiting".

Study Timeline

• Study First Submitted: 2023-09-20
• Study First Submitted QC: 2023-09-20
• Study First Posted: 2023-09-28
• Status Verified: 2024-07
• Study Start: 2024-07
• Last Update Submitted: 2024-07-02
• Last Update Posted: 2024-07-03
• Primary Completion: 2026-07
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Diagnosis of congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorder ≥6 months prior to the screening visit that is not attributable to medications, active or recent infections or malignancy.

• Have a confirmed trough ANC <1500 cells/µL during the screening visit (single ANC measurement) and at baseline visit (mean ANC over 6 hours) held at least 2 weeks prior to Day 1 dosing, with no clinical evidence of infection.

• Prior history of recurrent and/or serious infections during the 12 months preceding the screening visit (that is, suffering sequelae of chronic neutropenia), as defined by having at least 2 infections in the last 12 months that meet at least 1 of the following criteria:

  • Infection requiring the use of antibiotics (intravenous [IV]/oral/topical)
  • Infection requiring a visit to healthcare facility (including but not limited to emergency room visit, urgent care facility, primary care physician's office, or in-patient hospitalization).

• Participants who are on G-CSF or other active background therapy must have been receiving these therapies for ≥12 months, be on a stable dose and dosing schedule for ≥4 weeks prior to screening visit and remain on this dose and dosing schedule throughout the study (unless ANC >10,000 cells/µL for ≥4 weeks).

• Participants must be willing to keep their G-CSF or other background therapy doses/regimens stable (other than for safety reasons) for the duration of the study.

Key

Read More

Exclusion Criteria

• A diagnosis of secondary neutropenia including those due to:

  1. Hypersplenism
  2. Infection
  3. Malignancy
  4. Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, irritable bowel disease, graft-versus-host disease, thyroid disease
  5. Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition
  6. Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies.

• A diagnosis of any of the following:

  1. Aplastic anemia

  2. Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome

  3. Certain Congenital Neutropenias, including but not limited to these classifications are excluded:

     1. Isolated with a cyclic presentation, for example, elastase, neutrophil expressed (ELANE)
     2. Associated with immune dysregulation, for example, autoimmune lymphoproliferative syndrome, Familial hemophagocytic lymphohistiocytosis, Chédiak-Higashi syndrome
     3. Associated with bone marrow failure, for example, Fanconi Anemia, Diamond-Blackfan anemia, Telomere diseases

  4. Neutropenia associated with a Duffy-null phenotype (formerly known as benign ethnic neutropenia).

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

• Received more than 1 dose of mavorixafor in the past.

• Received C-X-C chemokine receptor 4 (CXCR4) antagonist (other than mavorixafor) in the past 6 months.

• Participants taking pegylated-G-CSF unless they have a diagnosis of congenital neutropenia confirmed at screening.

• Participant is currently taking or have taken other investigational drug at least 30 days prior to the screening visit.

Note: Other protocol-defined inclusion and exclusion criteria may apply.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mavorixafor	Mavorixafor	Participants will receive mavorixafor orally once daily starting from Day 1 through Week 52.
Placebo	Placebo	Participants will receive placebo to match mavorixafor orally once daily starting from Day 1 through Week 52.

Primary Outcome Measures

Name	Time	Method
Annualized Infection Rate Based on Infections Adjudicated by Blinded, Independent Adjudication Committee (BIAC) During the Treatment Period	Up to 52 Weeks
Number of Participants Meeting the Definition of a Positive Absolute Neutrophil Count (ANC) Response	Baseline, Week 52	Positive ANC response: ANC ≥1500 cells/microliter (µL), with the exception of participants with Baseline ANC \<500 cells/µL; and ≥2-fold increase in ANC from baseline, for participants with baseline ANC \< 500 cells/μL.

Secondary Outcome Measures

Name	Time	Method
Infection Severity Based on Common Terminology Criteria for Adverse Events (CTCAE) as Assessed by a BIAC During the Treatment Period	Up to 52 Weeks
Infection Duration Based on Duration of Infections Adjudicated by a BIAC During the Treatment Period in Those Participants who Developed Infections	Up to 52 Weeks
Antibiotic Use Due to Infection, Characterized by the Frequency of Antibiotic Use During the Treatment Period	Up to 52 Weeks
Oral Ulcers, as Assessed by Presence or Absence of Ulcers During the Treatment Period	Up to 52 Weeks
Change From Baseline in Patient Reported Outcomes Measurement Information System Short Form (PROMIS SF) Fatigue Questionnaire Total Score	Baseline, Week 52

Trial Locations

Locations (12)

LTD "Israeli-Georgian Medical Research Clinic Healthycore"; 🇬🇪 Tbilisi, Georgia

LEPL The First University Clinic of Tbilisi State Medical University; 🇬🇪 Tbilisi, Georgia

Hospital Universitario Son Espases; 🇪🇸 Mallorca, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

JSC K. Eristavi National Center of Experimental and Clinical Surgery; 🇬🇪 Tbilisi, Georgia

LTD Multiprofile Clinic Concilium Medulla; 🇬🇪 Tbilisi, Georgia

Hospital San Pedro De Alcantara; 🇪🇸 Cáceres, Spain

Icon Cancer Centre Southport; 🇦🇺 Southport, Australia

Universitaetsklinikum Carl Gustav Carus Tu Dresden; 🇩🇪 Dresden, Germany

Institutul Clinic Fundeni; 🇷🇴 Bucharest, Romania

Spitalul Clinic Județean de Urgență; 🇷🇴 Târgu-Mureş, Romania

Hospital Del Mar; 🇪🇸 Barcelona, Spain