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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections

Conditions
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Neutropenia

Intervention / Treatment
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* Drug: Mavorixafor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key 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 Exclusion Criteria: A diagnosis of secondary neutropenia including those due to: Hypersplenism Infection Malignancy Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, irritable bowel disease, graft-versus-host disease, thyroid disease Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies. A diagnosis of any of the following: Aplastic anemia Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome Certain Congenital Neutropenias, including but not limited to these classifications are excluded: Isolated with a cyclic presentation, for example, elastase, neutrophil expressed (ELANE) Associated with immune dysregulation, for example, autoimmune lymphoproliferative syndrome, Familial hemophagocytic lymphohistiocytosis, Chédiak-Higashi syndrome Associated with bone marrow failure, for example, Fanconi Anemia, Diamond-Blackfan anemia, Telomere diseases 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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mavorixafor<br>Participants will receive mavorixafor orally once daily starting from Day 1 through Week 52. | Drug: Mavorixafor<br>* Mavorixafor will be administered per schedule specified in the arm description.<br>* Other names: X4P-001;|
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to mavorixafor orally once daily starting from Day 1 through Week 52. | Drug: Placebo<br>* Placebo will be administered per schedule specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infection Rate Based on Infections Adjudicated by Blinded, Independent Adjudication Committee (AC) During the 12-Month Treatment Period |  | Baseline up to Month 12 | 
| Proportion of Participants Meeting the Definition of a Positive Absolute Neutrophil Count (ANC) Response During the First 3 Months | 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. | Baseline up to Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infection Severity Based on Severity of Infections Adjudicated by a Blinded Independent AC During the 12-Month Treatment Period |  | Baseline up to Month 12 | 
| Infection Duration Based on Duration of Infections Adjudicated by Blinded, Independent AC During the 12-Month Treatment Period in Those Participants who Developed Infections |  | Baseline up to Month 12 | 
| Antibiotic Use Due to Infection, Characterized by the Frequency of Antibiotic Use During the 12-Month Treatment Period |  | Baseline up to Month 12 | 
| Change From Baseline to Week 52 in Patient Reported Outcomes Measurement Information System Short Form (PROMIS SF) Fatigue Questionnaire Total Score |  | Baseline, Week 52 | 
| Oral Ulcers, as Assessed by Presence or Absence of Ulcers During the 12-Month Treatment Period |  | Baseline up to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCN, Mavorixafor, Chronic neutropenia, Chronic idiopathic neutropenia, CXCR4, Congenital and acquired neutropenia, autoimmune disease