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

NCT03995108 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: X4P-001-1032019-001153-104WHIM
• Study Type: interventional
• Target: 31
• Locations: 12 countries
• Sites: 21

Brief 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.

Conditions

WHIM Syndrome

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (52)

• 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

Study Arms (2)

Mavorixafor

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

Mavorixafor DRUG

Mavorixafor provided as 100 mg capsules.

Also known as: AMD11070, X4P-001

Mavorixafor; Placebo

Placebo DRUG

Placebo matching to mavorixafor capsules

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• X4 Pharmaceuticals: lead

Study Sites (23)

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

San Diego, California, 92123, United States

Location

California Dermatology Institute

Thousand Oaks, California, 91320, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University Medical Center

Baltimore, Maryland, 21224, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9020, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Wesley Hospital

Auchenflower, Queensland, 4006, Australia

Location

Children's Health Queensland Hospital

South Brisbane, Queensland, 4101, Australia

Location

Medical University of Vienna - Medizinische Universität Wien

Vienna, 1090, Austria

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

CHU de Lyon, Institut d'Hematologie et d'Oncologie Pediatrique

Lyon, Rhne, 69008, France

Location

CHU Paris Est, Hôpital d'Enfants Armand-Trousseau

Paris, 75571, France

Location

Hopital Necker-Enfants Malades

Paris, 75743, France

Location

University of Debrecen, Affiliated Department of Infectology

Debrecen, Hajdú-Bihar, H-4031, Hungary

Location

HaEmek Medical Center

Afula, 1834111, Israel

Location

Università degli Studi di Brescia, Scienze Cliniche e Sperimentali

Brescia, Piazza Del Mercato, 25123, Italy

Location

Emma Children's Hospital Academic Medical Center (AMC)

Amsterdam, 1105 AZ, Netherlands

Location

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Moscow, 117997, Russia

Location

Academician I.P. Pavlov First Saint Petersburg State Medical University

Saint Pertersburg, 197022, Russia

Location

Seoul National University Hospital, Children's Hospital

Seoul, 03080, South Korea

Location

Hospital Sant Joan de Deu Barcelona

Barcelona, Esplugues de Llobregat, 8950, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Sevilla, 41013, Spain

Location

Cukurova University Faculty of Medicine

Sarıçam, Adana, 1330, Turkey (Türkiye)

Location

Related Publications (1)

• Badolato R, Alsina L, Azar A, Bertrand Y, Bolyard AA, Dale D, Deya-Martinez A, Dickerson KE, Ezra N, Hasle H, Kang HJ, Kiani-Alikhan S, Kuijpers TW, Kulagin A, Langguth D, Levin C, Neth O, Olbrich P, Peake J, Rodina Y, Rutten CE, Shcherbina A, Tarrant TK, Vossen MG, Wysocki CA, Belschner A, Bridger GJ, Chen K, Dubuc S, Hu Y, Jiang H, Li S, MacLeod R, Stewart M, Taveras AG, Yan T, Donadieu J. A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome. Blood. 2024 Jul 4;144(1):35-45. doi: 10.1182/blood.2023022658.

  PMID: 38643510 DERIVED

MeSH Terms

Conditions

WHIM syndrome

Interventions

mavorixafor

Study Officials

• Chief Medical Officer

  X4 Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2019
• First Posted: June 21, 2019
• Study Start: October 24, 2019
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); IL (1); RU (2); ES (2); AU (1); FR (3); HU (1); DK (1); IT (1); NL (1); KR (1); TU (1)