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

Phase 3Active Not RecruitingNCT03995108

X4 Pharmaceuticals31 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

WHIM Syndrome

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Locations (23)

University of California San Diego Health/Rady Children's Hospital

San Diego, California, United States

California Dermatology Institute

Thousand Oaks, California, United States

University of Iowa

Iowa City, Iowa, United States

Johns Hopkins University Medical Center

Baltimore, Maryland, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

University of Washington Medical Center

Seattle, Washington, United States

Wesley Hospital

Auchenflower, Queensland, Australia

Children's Health Queensland Hospital

South Brisbane, Queensland, Australia

Medical University of Vienna - Medizinische Universität Wien

Vienna, Austria

Aarhus University Hospital

Aarhus, Denmark

...and 13 more locations

Outcomes

Primary Outcomes

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 frame: 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)

Time frame: 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 Outcomes

Randomized Placebo-Controlled Period: Time (in Hours) Above Threshold-Absolute Lymphocyte Count (TAT-ALC) of ≥ 1000 Cells/µL over a 24-hour period

Time frame: 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

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Change From Baseline in Total Warts Score at Week 52

Time frame: Baseline, Week 52

Randomized Placebo-Controlled Period: Total Infection Score for Mavorixafor

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Time to Early Release

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: TAT-ALC of ≥ 1000 Cells/µL in Participants With Lymphopenia

Time frame: Baseline

Randomized Placebo-Controlled Period: Total Infection Score for Participants With Non-Immunoglobulin (non-Ig) Use (Percentage of Participants With Infections)

Time frame: 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)

Time frame: 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.

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline (CGI-C), Based on Local Dermatologist Review

Time frame: Baseline

Randomized Placebo-Controlled Period: Participant Global Impression of Change (PGI-C)

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Participant Global Impression of Severity (PGI-S)

Time frame: 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

Time frame: 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)

Time frame: Week 52

Randomized Placebo-Controlled Period: Change From Baseline in Clinical Global Impression of Severity (CGI-S), Based on Local Dermatologist Review

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Number of Participants with Infections

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Infection-Free Time

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Number of Days Lost From Work/School

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Quality of Life as Measured by 36-Item Short Form Survey Score

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Quality of Life as Measured by EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Quality of Life as Measured by Life Quality Index (LQI) Score

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Quality of Life as Measured by Dermatology LQI Score

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) Score

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on Dermatologist CGI-C Assessment

Time frame: Baseline to Week 52

Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on AG Wart Severity Assessment

Time frame: Baseline to Week 52

Randomized Placebo-Controlled Period: Number of Events Requiring Rescue Treatment Due to Infection

Time frame: Baseline to Week 52

Randomized Placebo-Controlled Period: Number of Participants With Incidence and Duration of Hospitalizations Due to Infection

Time frame: Baseline to Week 52

Randomized Placebo-Controlled Period: Number of Participants With Incidence of Newly Developed Warts

Time frame: Baseline to Week 52

Randomized Placebo-Controlled Period: Area Under the Curve for ANC (AUCANC) Using Trapezoidal Method

Randomized Placebo-Controlled Period: Percentage of Neutrophil Responders

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Mavorixafor Treatment Group: AUCANC

Randomized Placebo-Controlled Period: Area Under the Curve for ALC (AUCALC)

Randomized Placebo-Controlled Period: Percentage of Lymphocyte Responders

Time frame: 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

Time frame: Baseline, Week 52

Absolute and Fold Change From Baseline in Absolute T, B and Natural Killer Lymphocyte at Week 52

Time frame: Baseline, Week 52

Randomized Placebo-Controlled Period: Number of Participants With AEs

Time frame: Baseline up to Week 52

Randomized Placebo-Controlled Period: Pharmacokinetics (PK), Maximum Observed Plasma Concentration (Cmax) of Mavorixafor

Time frame: 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 frame: 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

Randomized Placebo-Controlled Period: PK, Area Under the Curve (AUC) of Mavorixafor

Open-Label Period: Percentage of Neutrophil Responders

Time frame: Baseline up to Week 52 of open-label period

Open-Label Period: Percentage of Lymphocyte Responders

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline, Week 52 of open-label period

Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Central Review of CGI-S

Time frame: Baseline, Week 52 of open-label period

Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-C

Time frame: Baseline, Week 52 of open-label period

Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-S

Time frame: Baseline, Week 52 of open-label period

Open-Label Period: Change Over Time in PGI-C

Time frame: Baseline up to Week 52 of open-label period

Open-Label Period: Change Over Time in PGI-S

Time frame: Baseline up to Week 52 of open-label period

Open-Label Period: Total Infection Score (Percentage of Participants With Infections)

Time frame: Baseline up to Week 52 of open-label period