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

WHIM Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03995108
• Other study ID #: X4P-001-103
• Secondary ID: 2019-001153-104W
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 24, 2019
• Est. completion date: December 2024

Study information

• Verified date: October 2023
• Source: X4 Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Syndrome
• WHIM Syndrome

Intervention

Drug:
• Mavorixafor
Mavorixafor provided as 100 mg capsules.
• Placebo
Placebo matching to mavorixafor capsules

Locations

Country	Name	City	State
Australia	Wesley Hospital	Auchenflower	Queensland
Australia	Children's Health Queensland Hospital	South Brisbane	Queensland
Austria	Medical University of Vienna - Medizinische Universität Wien	Wien
Denmark	Aarhus University Hospital	Aarhus
France	CHU de Lyon, Institut d'Hematologie et d'Oncologie Pediatrique	Lyon	Rhne
France	Hopital Necker-Enfants Malades	Paris
France	CHU Paris Est, Hôpital d'Enfants Armand-Trousseau	Paris Cedex 12
Hungary	University of Debrecen, Affiliated Department of Infectology	Debrecen	Hajdu-Bihar
Israel	HaEmek Medical Center	Afula
Italy	Università degli Studi di Brescia, Scienze Cliniche e Sperimentali	Brescia	Piazza Del Mercato
Korea, Republic of	Seoul National University Hospital, Children's Hospital	Seoul
Netherlands	Emma Children's Hospital Academic Medical Center (AMC)	Amsterdam
Russian Federation	Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology	Moscow
Russian Federation	Academician I.P. Pavlov First Saint Petersburg State Medical University	Saint Pertersburg
Spain	Hospital Sant Joan de Deu Barcelona	Barcelona	Esplugues De Llobregat
Spain	Hospital Universitario Virgen del Rocío	Seville	Sevilla
Turkey	Cukurova University Faculty of Medicine	Saricam	Adana
United States	Johns Hopkins University Medical Center	Baltimore	Maryland
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of California San Diego Health/Rady Children's Hospital	San Diego	California
United States	University of Washington Medical Center	Seattle	Washington
United States	California Dermatology Institute	Thousand Oaks	California

Sponsors (1)

Lead Sponsor	Collaborator
X4 Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Denmark,  France,  Hungary,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Russian Federation,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Randomized Placebo-Controlled Period: Composite Clinical Efficacy for Mavorixafor based on total infection score and total wart change score		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Change From Baseline in Total Warts Score at Week 52		Baseline, Week 52
Secondary	Randomized Placebo-Controlled Period: Total Infection Score for Mavorixafor		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Time to Early Release		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: TAT-ALC of = 1000 Cells/µL in Participants With Lymphopenia		Baseline
Secondary	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
Secondary	Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline, Based on Clinical Global Impression of Change (CGI-C)		Baseline
Secondary	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
Secondary	Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline (CGI-C), Based on Local Dermatologist Review		Baseline
Secondary	Randomized Placebo-Controlled Period: Participant Global Impression of Change (PGI-C)		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Participant Global Impression of Severity (PGI-S)		Baseline up to Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	Randomized Placebo-Controlled Period: Number of Participants with Infections		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Infection-Free Time		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Number of Days Lost From Work/School		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Quality of Life as Measured by 36-Item Short Form Survey Score		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Quality of Life as Measured by EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Quality of Life as Measured by Life Quality Index (LQI) Score		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Quality of Life as Measured by Dermatology LQI Score		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) Score		Baseline up to Week 52
Secondary	Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on Dermatologist CGI-C Assessment		Baseline to Week 52
Secondary	Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on AG Wart Severity Assessment		Baseline to Week 52
Secondary	Randomized Placebo-Controlled Period: Number of Events Requiring Rescue Treatment Due to Infection		Baseline to Week 52
Secondary	Randomized Placebo-Controlled Period: Number of Participants With Incidence and Duration of Hospitalizations Due to Infection		Baseline to Week 52
Secondary	Randomized Placebo-Controlled Period: Number of Participants With Incidence of Newly Developed Warts		Baseline to Week 52
Secondary	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
Secondary	Randomized Placebo-Controlled Period: Percentage of Neutrophil Responders		Baseline up to Week 52
Secondary	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
Secondary	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
Secondary	Randomized Placebo-Controlled Period: Percentage of Lymphocyte Responders		Baseline up to Week 52
Secondary	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
Secondary	Absolute and Fold Change From Baseline in Absolute T, B and Natural Killer Lymphocyte at Week 52		Baseline, Week 52
Secondary	Randomized Placebo-Controlled Period: Number of Participants With AEs		Baseline up to Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Open-Label Period: Percentage of Neutrophil Responders		Baseline up to Week 52 of open-label period
Secondary	Open-Label Period: Percentage of Lymphocyte Responders		Baseline up to Week 52 of open-label period
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Central Review of CGI-S		Baseline, Week 52 of open-label period
Secondary	Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-C		Baseline, Week 52 of open-label period
Secondary	Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-S		Baseline, Week 52 of open-label period
Secondary	Open-Label Period: Change Over Time in PGI-C		Baseline up to Week 52 of open-label period
Secondary	Open-Label Period: Change Over Time in PGI-S		Baseline up to Week 52 of open-label period
Secondary	Open-Label Period: Total Infection Score (Percentage of Participants With Infections)		Baseline up to Week 52 of open-label period