Clinical trial NCT03005327: A Dose Determination and Safety Study of X4P-001 (Mavorixafor) in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome
Official title: A Phase 2, Open-Label, Multi-Center Trial of Mavorixafor in Patients With WHIM Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: WHIM Syndrome
Lead sponsor: X4 Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-12-29
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC)
timeFrame: 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
measure: All Visits: Average Per-Participant Value of the AUCANC
timeFrame: 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
measure: Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC)
timeFrame: 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
measure: All Visits: Average Per-Participant Value of the AUCALC
timeFrame: 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
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug through 10 days after the last dose of the study drug (Maximum exposure: 1712 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital
state: Victoria
Study officials:
References:
citation: Dale DC, Firkin F, Bolyard AA, Kelley M, Makaryan V, Gorelick KJ, Ebrahim T, Garg V, Tang W, Jiang H, Skerlj R, Beaussant Cohen S. Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome. Blood. 2020 Dec 24;136(26):2994-3003. doi: 10.1182/blood.2020007197.