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

Sponsor

X4 Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06056297

Collaborator

(none)

128

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 increasing levels of circulating neutrophils as well as demonstrating its clinical benefit.

Condition or Disease	Intervention/Treatment	Phase
Neutropenia	Drug: Mavorixafor Drug: Placebo	Phase 3

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, G CSF, immunoglobulin replacement therapy, prophylactic antibiotics, or "watchful waiting".

Study Design

Study Type:

Interventional

Anticipated Enrollment :

128 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2024

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Mavorixafor

Participants will receive mavorixafor orally once daily starting from Day 1 through Week 52.

Drug: Mavorixafor

Mavorixafor will be administered per schedule specified in the arm description.

Other Names:

X4P-001

Placebo Comparator: Placebo

Participants will receive placebo matching to mavorixafor orally once daily starting from Day 1 through Week 52.

Drug: Placebo

Placebo will be administered per schedule specified in the arm description.

Outcome Measures

Primary Outcome Measures

Number of Participants Meeting the Definition of a Positive Absolute Neutrophil Count (ANC) Response During the First 3 Months [Baseline up to Month 3]
Positive ANC response: ANC ≥1500 cells/microliter (µL), with the exception of participants with severe congenital neutropenia (SCN); Baseline ANC <500 cells/µL; positive response is defined as a ≥ 2-fold increase in ANC from baseline.
Number of Participants With Decreased Infection Based on Infections Adjudicated by Blinded, Independent Adjudication Committee (AC) During the 12-Month Treatment Period [Baseline up to Month 12]

Secondary Outcome Measures

Number of Participants not on Chronic Granulocyte-colony Stimulating Factor (G-CSF) Treatment Meeting the definition of a Positive ANC Response During the First 3 Months [Baseline up to Month 3]
Positive ANC response: ANC ≥1500 cells/ µL, with the exception of participants with SCN; Baseline ANC <500 cells/µL; positive response is defined as a ≥ 2-fold increase in ANC from baseline.
Number of Participants not on Chronic G-CSF Treatment, With Decreased Infection Based on Infections Adjudicated by Blinded, Independent AC During the 12-Month Treatment Period [Baseline up to Month 12]
Change From Baseline in Patient Reported Outcomes Measurement Information System Short Form (PROMIS SF) Fatigue Questionnaire Total Score at Week 52 [Baseline, Week 52]
Number of Participants With Oral Ulcers [Baseline up to Month 12]
Number of Participants who Use Antibiotics Due to Infection [Baseline up to Month 12]
Duration of Positive ANC Response [Baseline up to Month 12]
Duration of Positive ANC Response in Participants not Receiving Chronic G-CSF [Baseline up to Month 12]
Number of Participants with an Overall Positive ANC Response 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]
Total Absolute Lymphocyte Count [Baseline up to Month 12]
Absolute Monocyte Count (AMC) [Baseline up to Month 12]
ANC [Baseline up to Month 12]
White Blood Cell Count [Baseline up to Month 12]
Number of Participants With Decreased Severity of Infections Adjudicated by Blinded, Independent AC During the 12-Month Treatment Period [Baseline up to Month 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
Participants who are on G-CSF or other active SoC 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 doses/regimens stable (other than for safety reasons) for the duration of the trial.

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).

Known active COVID-19 infection or a positive test within the local accepted clinical and governmental guidelines for a communicable window.
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.