NCT03005327

A Phase 2, Open-Label, Multi-Center Trial of Mavorixafor in Patients With WHIM Syndrome

Completed Phase 2 Results posted Last updated 8 October 2024

What this trial tests

Phase 2 trial testing X4P-001 in WHIM Syndrome in 8 participants. Completed in 16 June 2022.

Timeline

1 December 2016

Primary endpoint
16 June 2022

16 June 2022

Quick facts

Lead sponsor	X4 Pharmaceuticals
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	8
Start date	1 December 2016
Primary completion	16 June 2022
Estimated completion	16 June 2022
Sites	2 locations across United States, Australia

Drugs / interventions tested

• X4P-001 — full drug profile →

Conditions studied

• WHIM Syndrome — all drugs for WHIM Syndrome →

Sponsor

X4 Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with WHIM Syndrome. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC)
  Time frame: Time 0 (-15 minutes [min] pre-dose), 30, 60, and 90 min (each ± 5 min) and 2, 3, 4, 8, 12, 16, and 24 hours (each ±15 min) at Weeks 5, 13, and 21
  AUCANC was collected over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated participants over 6 months. The absolute neutrophil count (ANC) clinically meaningful threshold was defined as ANC ≥ 600/microliter (μL).
• All Visits: Average Per-Participant Value of the AUCANC
  Time frame: Time 0 (-15 min pre-dose), 30, 60, and 90 min (each ± 5 min) and 2, 3, 4, 8, 12, 16, and 24 hours (each ±15 min) at Weeks 5, 13, and 21
  AUCANC was collected over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated participants over 6 months. The ANC clinically meaningful threshold was defined as ANC ≥ 600/μL. Data for this outcome measure are reported as an "All Visits" summary based on the mean of AUCs that is, the per-participant average of the AUCANC across the 3 visits where participant was tre
• Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC)
  Time frame: Time 0 (-15 min pre-dose), 30, 60, and 90 min (each ± 5 min) and 2, 3, 4, 8, 12, 16, and 24 hours (each ±15 min) at Weeks 5, 13, and 21
  AUCALC was collected over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated participants over 6 months. The absolute lymphocyte count (ALC) clinically meaningful threshold was defined as ALC ≥ 1000/μL.
• All Visits: Average Per-Participant Value of the AUCALC
  Time frame: Time 0 (-15 min pre-dose), 30, 60, and 90 min (each ± 5 min) and 2, 3, 4, 8, 12, 16, and 24 hours (each ±15 min) at Weeks 5, 13, and 21
  AUCALC was collected over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated participants over 6 months. The ALC clinically meaningful threshold was defined as ALC ≥ 1000/μL. Data for this outcome measure are reported as an "All Visits" summary based on the mean of AUCs that is, the per-participant average of the AUCALC across the 3 visits where participant was tr
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
  Time frame: From first dose of study drug through 10 days after the last dose of the study drug (Maximum exposure: 1712 days)
  An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and did not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a con

Sponsor's own description

This is a Phase 2 study with an initial 24-week Treatment Period and an Extension Phase. The primary objectives of this Phase 2 study are to determine the safety, tolerability, and dose selection of mavorixafor in participants with WHIM syndrome. Participants may continue treatment in an Extension Phase, if regionally applicable, until mavorixafor becomes available via an alternative mechanism (for example, drug is commercially available, an expanded access program, etc.) or until the study is terminated by the Sponsor for any reason.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
   Cambier S, Gouwy M, Proost P. · · 2023 · cited 387× · PMID 36725964 · DOI 10.1038/s41423-023-00974-6
2. CXCR4 and CXCR7 Signaling Pathways: A Focus on the Cross-Talk Between Cancer Cells and Tumor Microenvironment.
   Santagata S, Ieranò C, Trotta AM, Capiluongo A, et al · · 2021 · cited 74× · PMID 33937018 · DOI 10.3389/fonc.2021.591386
3. Multisystem multitasking by CXCL12 and its receptors CXCR4 and ACKR3.
   Murphy PM, Heusinkveld L. · · 2018 · cited 56× · PMID 29398278 · DOI 10.1016/j.cyto.2017.12.022
4. Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome.
   Dale DC, Firkin F, Bolyard AA, Kelley M, et al · · 2020 · cited 49× · PMID 32870250 · DOI 10.1182/blood.2020007197
5. A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome.
   Badolato R, Alsina L, Azar A, Bertrand Y, et al · · 2024 · cited 42× · PMID 38643510 · DOI 10.1182/blood.2023022658
6. Pathogenesis, diagnosis and therapeutic strategies in WHIM syndrome immunodeficiency.
   Heusinkveld LE, Yim E, Yang A, Azani AB, et al · · 2017 · cited 40× · PMID 29057173 · DOI 10.1080/21678707.2017.1375403
7. Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization.
   Jørgensen AS, Daugvilaite V, De Filippo K, Berg C, et al · · 2021 · cited 34× · PMID 33980979 · DOI 10.1038/s42003-021-02070-9
8. Genotype-phenotype correlations in WHIM syndrome: a systematic characterization of CXCR4^WHIM variants.
   Zmajkovicova K, Pawar S, Maier-Munsa S, Maierhofer B, et al · · 2022 · cited 13× · PMID 36089616 · DOI 10.1038/s41435-022-00181-9