A Dose Determination and Safety Study of X4P-001 (Mavorixafor) in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome

Phase 2

Completed

• Conditions: WHIM Syndrome
• Interventions: Drug: X4P-001

• Registration Number: NCT03005327
• Lead Sponsor: X4 Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12
• Study First Submitted: 2016-12-20
• Study First Submitted QC: 2016-12-23
• Study First Posted: 2016-12-29
• Primary Completion: 2022-06-16
• Study Completion: 2022-06-16
• Results First Submitted: 2024-05-28
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-08
• Last Update Submitted: 2024-10-08
• Results First Posted: 2024-10-30
• Last Update Posted: 2024-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

Participants with a clinical diagnosis of WHIM syndrome must meet all of the following criteria to be eligible for study participation:

1. Be at least 18 years of age.
2. Has signed the current approved informed consent form.
3. Has a genotype-confirmed mutation of chemokine receptor type 4 (CXCR4) consistent with WHIM syndrome.
4. Agree to use effective contraception.
5. Be willing and able to comply with this protocol.
6. Has confirmed ANC less than or equal to (≤) 400/µL or ALC ≤650/µL or both.

Exclusion Criteria

Participants with any of the following will be excluded from participation in the study:

1. Has known systemic hypersensitivity to the mavorixafor drug substance or its inactive ingredients.

2. Is pregnant or nursing.

3. Has a known history of a positive serology or viral load for human immunodeficiency virus (HIV) or a known history of acquired immunodeficiency syndrome (AIDS).

4. Has, at Screening, laboratory tests meeting one or more of the following criteria:

   • A positive antibody test for hepatitis C virus (HCV), unless documented to have no detectable viral load on 2 independent samples.
   • A positive test for hepatitis B surface antigen (HBsAg).

5. Has any medical or personal condition that, 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
X4P-001	X4P-001	Initial Treatment Phase: Participants will initiate treatment with mavorixafor at 50 milligrams (mg) once daily (QD) orally or a higher dose, with potential escalation based on area under the curve for absolute neutrophil count and absolute leukocyte count (AUCANC/ALC) values to a maximum total daily dose of 400 mg. Participants are expected to receive treatment for 24 weeks in the initial Treatment Period or until development of a treatment-limiting toxicity (TLT). Extension Phase: All participants will receive mavorixafor; the dose will not exceed 400 mg. In the Extension Phase, treatment may continue 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.

Primary Outcome Measures

Name	Time	Method
Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC)	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 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 treated with at least 300/400 mg dose. Time frame reported is based on data collection time points.
Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC)	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 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 treated with at least 300/400 mg dose. Time frame reported is based on data collection time points.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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 congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was defined as any AE that began or worsened in severity or frequency on or after the start of study drug through 10 days after the last dose of the study drug. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.

Trial Locations

Locations (2)

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States

St. Vincent's Hospital; 🇦🇺 Fitzroy, Victoria, Australia