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

Overview

This study has a double-blind, placebo-controlled Randomized Period and an Open-Label extension Period. The primary objective of the Randomized 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 extension Period, if regionally applicable, until mavorixafor becomes commercially available, or until the study is terminated by the Sponsor.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: September 2021

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Mavorixafor
    • Participants will receive mavorixafor 400 milligrams (mg) once daily orally for 52 weeks in the Randomized Period. Participants who complete the Randomized 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.
  • Placebo Comparator: Placebo
    • Participants will receive placebo matching to mavorixafor once daily orally for 52 weeks in the Randomized Period. Participants who complete the Randomized 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.

Clinical Trial Outcome Measures

Primary Measures

  • Randomized Period: Time (in Hours) Above Absolute Neutrophil Count (ANC) Threshold of 500 Cells/Microliter (µL)
    • 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 Measures

  • Randomized Period: Area Under the Curve for ANC (AUCANC) Using Trapezoidal Method
    • 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 Period: Infection Rate (Percentage of Participants With Infections) Based on Infections Adjudicated by a Blinded, Independent AC
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Number of Proactive Vaccine Titers at Week 52
    • Time Frame: Week 52
  • Randomized Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Dermatologist Clinical Global Impression of Change
    • Time Frame: Baseline, Week 52
  • Randomized Period: Percentage of Neutrophil Responders
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Mavorixafor Treatment Group: AUCANC
    • 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 Period: Time (in Hours) Above Absolute Lymphocyte Count (ALC) Threshold of 1000 Cells/µL
    • 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 Period: Area Under the Curve for ALC (AUCALC)
    • 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 Period: Percentage of Lymphocyte Responders
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Duration of Infection
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Infection Characteristics, The Number of Participants With Severe Infections
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Infection-Free Time
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Number of Days Lost From Work/School
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Quality of Life as Measured by 36-Item Short Form Survey Score
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) Score
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Quality of Life as Measured by EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Quality of Life as Measured by Life Quality Index (LQI) Score
    • Time Frame: Baseline up to Week 52
  • Randomized Period: Quality of Life as Measured by Dermatology LQI Score
    • Time Frame: Baseline up to Week 52
  • Randomized 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 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 Period: PK, Half-Life of (T1/2) 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 Period: PK, Area Under the Curve (AUC) 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
  • Open-Label Period: Number of Proactive Vaccine Titers at Week 13
    • Time Frame: Week 13 of open-label period
  • Open-Label Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Dermatologist Clinical Global Impression of Change
    • Time Frame: Baseline, Week 52 of open-label period
  • Open-Label Period: Infection Rate (Percentage of Participants With Infections) Based on Infections Adjudicated by a Blinded, Independent AC
    • Time Frame: Baseline up to Week 52 of open-label period

Participating in This Clinical Trial

Inclusion Criteria

  • Be at least 12 years of age and Tanner stage greater than or equal to (≥) 3. – 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. 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 nursing. – 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. Exclusion Criteria for the Open-Label Period: – Participants who experience any treatment-limiting toxicity (TLT) will be excluded from participating in the Open-Label Period.
  • Gender Eligibility: All

    Minimum Age: 12 Years

    Maximum Age: N/A

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • X4 Pharmaceuticals
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Chief Medical Officer, Study Director, X4 Pharmaceuticals
    • Overall Contact(s)
      • X4 Pharmaceuticals, 857-529-5779, patientinfo@x4pharma.com

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