Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Mavorixafor in Patients With WHIM Syndrome With Open-Label Extension

This study has a double-blind, Randomized Placebo-Controlled Period and an Open-Label Period. The primary objective of the Randomized Placebo-Controlled Period is to demonstrate the efficacy of mavorixafor in participants with WHIM syndrome as assessed by increasing levels of circulating neutrophils compared with placebo, and relative to a clinically meaningful threshold. The primary objective of the Open-Label Period is to evaluate the safety and tolerability of mavorixafor in participants with WHIM syndrome. Participants are allowed to continue treatment in the Open-Label Period, if regionally applicable, until mavorixafor becomes commercially available, or until the study is terminated by the Sponsor.

Study Overview

• Status: Active, not recruiting
• Conditions: WHIM Syndrome
• Intervention / Treatment: Drug: Mavorixafor; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Auchenflower, Queensland, Australia, 4006
      • Wesley Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Children's Health Queensland Hospital
• Austria
  • Wien, Austria, 1090
    • Medical University of Vienna - Medizinische Universität Wien
• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital
• France
  • Paris, France, 75743
    • Hopital Necker-Enfants Malades
  • Paris Cedex 12, France, 75571
    • CHU Paris Est, Hôpital d'Enfants Armand-Trousseau
  • Rhne
    • Lyon, Rhne, France, 69008
      • CHU de Lyon, Institut d'Hematologie et d'Oncologie Pediatrique
• Hungary
  • Hajdu-Bihar
    • Debrecen, Hajdu-Bihar, Hungary, H-4031
      • University of Debrecen, Affiliated Department of Infectology
• Israel
  • Afula, Israel, 1834111
    • Haemek Medical Center
• Italy
  • Piazza Del Mercato
    • Brescia, Piazza Del Mercato, Italy, 25123
      • Università degli Studi di Brescia, Scienze Cliniche e Sperimentali
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital, Children's Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Emma Children's Hospital Academic Medical Center (AMC)
• Russian Federation
  • Moscow, Russian Federation, 117997
    • Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
  • Saint Pertersburg, Russian Federation, 197022
    • Academician I.P. Pavlov First Saint Petersburg State Medical University
• Spain
  • Esplugues De Llobregat
    • Barcelona, Esplugues De Llobregat, Spain, 8950
      • Hospital Sant Joan de Déu Barcelona
  • Sevilla
    • Seville, Sevilla, Spain, 41013
      • Hospital Universitario Virgen Del Rocio
• Turkey
  • Adana
    • Sarıcam, Adana, Turkey, 1330
      • Cukurova University Faculty of Medicine
• United States
  • California
    • San Diego, California, United States, 92123
      • University of California San Diego Health/Rady Children's Hospital
    • Thousand Oaks, California, United States, 91320
      • California Dermatology Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-9020
      • University of Texas Southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for the Randomized Placebo-Controlled Period :

• Have signed the current approved informed consent form. Participants under 18 years of age (in the Netherlands and other applicable regions, participants under 16 years of age) will sign an approved informed assent form and must also have a signed parental/legal guardian consent.
• Have a genotype-confirmed mutation of chemokine (C-X-C motif) receptor 4 (CXCR4) consistent with WHIM phenotype.
• Agree to use a highly effective form of contraception.
• Be willing and able to comply with the protocol.
• Have confirmed ANC ≤400 cells/µL during screening, obtained while participant has no clinical evidence of infection.

Inclusion Criteria for the Open-Label Period:

• Completed the Randomized Period; or
• Granted Early Release from the Randomized Period.

Exclusion Criteria:

• Has known systemic hypersensitivity to the mavorixafor drug substance, its inactive ingredients, or the placebo.
• Is pregnant or breastfeeding.
• Has any medical or personal condition, which 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mavorixafor; Participants (adults and adolescents [12 to 17 years of age weighing >50 kilograms [kg]) will receive mavorixafor 400 milligrams (mg) once daily (QD) orally for 52 weeks in the Randomized Placebo-Controlled Period. Adolescents weighing ≤50 kg will receive mavorixafor 200 mg QD. Participants who complete the Randomized Placebo-Controlled Period or are granted Early Release due to recurrent or significant infections, as adjudicated by a blinded, independent adjudication committee (AC), will be offered the opportunity to enroll in the Open-Label Period and receive treatment with mavorixafor 400 mg once daily orally until commercial availability or study termination by the Sponsor.	Drug: Mavorixafor; Mavorixafor provided as 100 mg capsules.; Other Names: AMD11070, X4P-001
Placebo Comparator: Placebo; Participants will receive placebo matching to mavorixafor QD orally for 52 weeks in the Randomized Placebo-Controlled Period. Participants who complete the Randomized Placebo-Controlled Period or are granted Early Release due to recurrent or significant infections, as adjudicated by a blinded, independent AC, will be offered the opportunity to enroll in the Open-Label Period and receive treatment with mavorixafor 400 mg once daily orally until commercial availability or study termination by the Sponsor.	Drug: Mavorixafor; Mavorixafor provided as 100 mg capsules.; Other Names: AMD11070, X4P-001; Drug: Placebo; Placebo matching to mavorixafor capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Randomized Placebo-Controlled Period: Time (in Hours) Above Threshold-Absolute Neutrophil Count (TAT-ANC in hours) of ≥ 500 Cells/Microliter (µL) over a 24-hour period	Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 min (each ± 5 min) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 min) post-dose at Baseline, Weeks 13, 26, 39, and 52
Open-Label Period: Percentage of Participants With Adverse Events (AEs)	From Day 1 (end of randomized period) up to end of study (30 days post-treatment in open-label period [Week 56 of open-label period])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Randomized Placebo-Controlled Period: Time (in Hours) Above Threshold-Absolute Lymphocyte Count (TAT-ALC) of ≥ 1000 Cells/µL over a 24-hour period		Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 minutes) post-dose at Baseline, Weeks 13, 26, 39, and 52
Randomized Placebo-Controlled Period: Composite Clinical Efficacy for Mavorixafor based on total infection score and total wart change score		Baseline up to Week 52
Randomized Placebo-Controlled Period: Change From Baseline in Total Warts Score at Week 52		Baseline, Week 52
Randomized Placebo-Controlled Period: Total Infection Score for Mavorixafor		Baseline up to Week 52
Randomized Placebo-Controlled Period: Time to Early Release		Baseline up to Week 52
Randomized Placebo-Controlled Period: TAT-ALC of ≥ 1000 Cells/µL in Participants With Lymphopenia		Baseline
Randomized Placebo-Controlled Period: Total Infection Score for Participants With Non-Immunoglobulin (non-Ig) Use (Percentage of Participants With Infections)		Baseline up to Week 52
Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline, Based on Clinical Global Impression of Change (CGI-C)		Baseline
Randomized Placebo-Controlled Period: Composite Clinical Efficacy (Total Infection Score and Total Wart Change Score) for Participants With Non-Ig Use	Composite clinical efficacy will be calculated using the total infection score and total wart change score for participants with warts at baseline or non-Ig use. It will be analyzed by a blinded, independent AC.	Baseline up to Week 52
Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline (CGI-C), Based on Local Dermatologist Review		Baseline
Randomized Placebo-Controlled Period: Participant Global Impression of Change (PGI-C)		Baseline up to Week 52
Randomized Placebo-Controlled Period: Participant Global Impression of Severity (PGI-S)		Baseline up to Week 52
Randomized Placebo-Controlled Period: Vaccine Titer Levels at Week 52 in Participants Vaccinated at Week 13, With Tetanus, Diphtheria, and Pertussis (Tdap) Including Pertussis Toxin, and Tetanus		Week 52
Randomized Placebo-Controlled Period: Vaccine Titer Levels at Week 52 for Human Papillomavirus (HPV) 16 and HPV 18 in Participants Receiving Vaccinations With HPV 9-Valent Vaccine, Recombinant (Gardasil®9)		Week 52
Randomized Placebo-Controlled Period: Change From Baseline in Clinical Global Impression of Severity (CGI-S), Based on Local Dermatologist Review		Baseline up to Week 52
Randomized Placebo-Controlled Period: Number of Participants with Infections		Baseline up to Week 52
Randomized Placebo-Controlled Period: Infection-Free Time		Baseline up to Week 52
Randomized Placebo-Controlled Period: Number of Days Lost From Work/School		Baseline up to Week 52
Randomized Placebo-Controlled Period: Quality of Life as Measured by 36-Item Short Form Survey Score		Baseline up to Week 52
Randomized Placebo-Controlled Period: Quality of Life as Measured by EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score		Baseline up to Week 52
Randomized Placebo-Controlled Period: Quality of Life as Measured by Life Quality Index (LQI) Score		Baseline up to Week 52
Randomized Placebo-Controlled Period: Quality of Life as Measured by Dermatology LQI Score		Baseline up to Week 52
Randomized Placebo-Controlled Period: Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) Score		Baseline up to Week 52
Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on Dermatologist CGI-C Assessment		Baseline to Week 52
Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on AG Wart Severity Assessment		Baseline to Week 52
Randomized Placebo-Controlled Period: Number of Events Requiring Rescue Treatment Due to Infection		Baseline to Week 52
Randomized Placebo-Controlled Period: Number of Participants With Incidence and Duration of Hospitalizations Due to Infection		Baseline to Week 52
Randomized Placebo-Controlled Period: Number of Participants With Incidence of Newly Developed Warts		Baseline to Week 52
Randomized Placebo-Controlled Period: Area Under the Curve for ANC (AUCANC) Using Trapezoidal Method		Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 minutes) post-dose at Baseline, Weeks 13, 26, 39, and 52
Randomized Placebo-Controlled Period: Percentage of Neutrophil Responders		Baseline up to Week 52
Randomized Placebo-Controlled Period: Mavorixafor Treatment Group: AUCANC		Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 minutes) post-dose at Baseline, Weeks 13, 26, 39, and 52
Randomized Placebo-Controlled Period: Area Under the Curve for ALC (AUCALC)		Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 minutes) post-dose at Baseline, Weeks 13, 26, 39, and 52
Randomized Placebo-Controlled Period: Percentage of Lymphocyte Responders		Baseline up to Week 52
Randomized Placebo-Controlled Period: Change From Baseline in Total ALC, Absolute Monocyte Count (AMC), ANC, and White Blood Cell (WBC) at Week 52		Baseline, Week 52
Absolute and Fold Change From Baseline in Absolute T, B and Natural Killer Lymphocyte at Week 52		Baseline, Week 52
Randomized Placebo-Controlled Period: Number of Participants With AEs		Baseline up to Week 52
Randomized Placebo-Controlled Period: Pharmacokinetics (PK), Maximum Observed Plasma Concentration (Cmax) of Mavorixafor		Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 minutes) post-dose at Weeks 13, 26, 39, and 52; and 4 hours post-dose at Baseline
Randomized Placebo-Controlled Period: PK, Time to Reach Cmax (Tmax) of Mavorixafor		Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 min (each ± 5 minutes) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 minutes) post-dose at Weeks 13, 26, 39, and 52; and 4 hours post-dose at Baseline
Randomized Placebo-Controlled Period: PK, Half-Life of (T1/2) of Mavorixafor		Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 minutes) post-dose at Weeks 13, 26, 39, and 52; and 4 hours post-dose at Baseline
Randomized Placebo-Controlled Period: PK, Area Under the Curve (AUC) of Mavorixafor		Time 0 (pre-dose, up to 15 minutes prior), 30, 60, and 90 minutes (each ± 5 minutes) and 2, 3, 4, 8, 12, 16, and 24 hours (each ± 15 minutes) post-dose at Weeks 13, 26, 39, and 52; and 4 hours post-dose at Baseline
Open-Label Period: Percentage of Neutrophil Responders		Baseline up to Week 52 of open-label period
Open-Label Period: Percentage of Lymphocyte Responders		Baseline up to Week 52 of open-label period
Open-Label Period: Absolute and Fold Change From Baseline in Total ALC, AMC, ANC, and WBC at Week 52		Baseline up to Week 52 of open-label period
Open-Label Period: Vaccine Titer Levels During the First Year of Open-Label Period, in Participants Vaccinated With Tdap During the Study Including Pertusis Toxin and Tetanus		Year 1 of open-label period
Open-Label Period: Vaccine Titer Levels During the First Year of the Open-Label Period for HPV 16 and HPV 18 in Participants Receiving Vaccinations With HPV 9-Valent Vaccine, Recombinant (Gardasil®9) During the Study		Year 1 of open-label period
Open-Label Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Central Review of CGI-C		Baseline, Week 52 of open-label period
Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Central Review of CGI-S		Baseline, Week 52 of open-label period
Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-C		Baseline, Week 52 of open-label period
Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-S		Baseline, Week 52 of open-label period
Open-Label Period: Change Over Time in PGI-C		Baseline up to Week 52 of open-label period
Open-Label Period: Change Over Time in PGI-S		Baseline up to Week 52 of open-label period
Open-Label Period: Total Infection Score (Percentage of Participants With Infections)		Baseline up to Week 52 of open-label period

Collaborators and Investigators

• Sponsor: X4 Pharmaceuticals
• Investigators: Study Director: Chief Medical Officer, X4 Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2019
• Primary Completion (Actual): October 10, 2022
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: June 19, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome
• Other Study ID Numbers: X4P-001-103; 2019-001153-10 (EudraCT Number); 4WHIM (Other Identifier: X4 Pharmaceuticals)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No