WHIM Syndrome
Conditions
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.
Interventions
DRUGX4P-001
Mavorixafor will be provided as either 25 mg or 100 mg capsules.
Sponsors
X4 Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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'. |
Countries
Australia, United States
Participant flow
Pre-assignment details
Each participant was treated at doses that were increased up to a maximum total daily dose of 400 milligrams (mg) based on their individual area under the curve for absolute neutrophil count and absolute leukocyte count (AUCANC/ALC) values.
Participants by arm
| Arm | Count |
|---|---|
| X4P-001 Participants received X4P-001 (mavorixafor) orally QD at doses between 50 mg and 400 mg for the Initial Treatment Period (24 weeks) and could continue participation in the open-label Extension Phase until experiencing a TLT event, X4P-001 was available commercially, or until the study was terminated by the Sponsor. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Initial Treatment Period (24 Weeks) | Adverse Event | 0 | 0 | 1 | 0 |
| Initial Treatment Period (24 Weeks) | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | X4P-001 |
|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 13.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 7 | 0 / 5 | 0 / 8 |
| other Total, other adverse events | 2 / 2 | 2 / 4 | 2 / 3 | 2 / 4 | 6 / 7 | 3 / 5 | 7 / 8 |
| serious Total, serious adverse events | 0 / 2 | 0 / 4 | 0 / 3 | 0 / 4 | 2 / 7 | 1 / 5 | 3 / 8 |
Outcome results
Primary
All Visits: Average Per-Participant Value of the AUCALC
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.
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
Population: The Safety Population included all participants who received at least 1 dose of the study medication (mavorixafor). Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| X4P-001 50 mg | All Visits: Average Per-Participant Value of the AUCALC | 14232.17 cells*hour/μL | Standard Deviation 16789.7 |
Primary
All Visits: Average Per-Participant Value of the AUCANC
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.
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
Population: The Safety Population included all participants who received at least 1 dose of the study medication (mavorixafor). Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| X4P-001 50 mg | All Visits: Average Per-Participant Value of the AUCANC | 27477.00 cells*hour/μL | Standard Deviation 55792.377 |
Primary
Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC)
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.
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
Population: Overall Number of Participants Analyzed=number of participants in safety population (all participants who received at least 1 dose of study medication). 'Number analyzed'=number of participants with data above clinically meaningful thresholds at specified timepoints. Participants included in 1 category may be different than participants in other categories. Data for this Outcome Measure were collected by dose level; therefore, participants may have been included in more than 1 arm (dose level).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| X4P-001 50 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 5 | -5839.54 cells*hour/μL | Standard Deviation 6485.407 |
| X4P-001 100 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 13 | -1006.50 cells*hour/μL | Standard Deviation 10546.262 |
| X4P-001 100 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 5 | 6978.25 cells*hour/μL | Standard Deviation 7435.935 |
| X4P-001 150 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 21 | -2216.17 cells*hour/μL | Standard Deviation 8285.642 |
| X4P-001 200 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 13 | 7023.83 cells*hour/μL | Standard Deviation 1603.482 |
| X4P-001 200 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 5 | 4783.33 cells*hour/μL | — |
| X4P-001 300 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 13 | 2862.50 cells*hour/μL | — |
| X4P-001 300 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 5 | 21837.50 cells*hour/μL | Standard Deviation 24236.085 |
| X4P-001 300 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 21 | 15331.35 cells*hour/μL | Standard Deviation 21250.202 |
| X4P-001 300/400 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 5 | 21837.50 cells*hour/μL | Standard Deviation 24236.085 |
| X4P-001 300/400 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 13 | 2862.50 cells*hour/μL | — |
| X4P-001 300/400 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Lymphocyte Count (AUCALC) | Week 21 | 15331.35 cells*hour/μL | Standard Deviation 21250.202 |
Primary
Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC)
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).
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
Population: Overall Number of Participants Analyzed=number of participants in safety population (all participants who received at least 1 dose of study medication). 'Number analyzed'=number of participants with data above clinically meaningful thresholds at specified timepoints. Participants included in 1 category may be different than participants in other categories. Data for this Outcome Measure were collected by dose level; therefore, participants may have been included in more than 1 arm (dose level).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| X4P-001 50 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 5 | -12574.63 cells*hour/μL | Standard Deviation 156.094 |
| X4P-001 100 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 13 | -11291.96 cells*hour/μL | Standard Deviation 1509.496 |
| X4P-001 100 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 5 | -6206.75 cells*hour/μL | Standard Deviation 4238.28 |
| X4P-001 150 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 21 | -8723.00 cells*hour/μL | Standard Deviation 2695.962 |
| X4P-001 200 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 13 | -7575.21 cells*hour/μL | Standard Deviation 2701.443 |
| X4P-001 200 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 5 | -6949.58 cells*hour/μL | — |
| X4P-001 300 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 13 | -2602.50 cells*hour/μL | — |
| X4P-001 300 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 5 | 24175.00 cells*hour/μL | Standard Deviation 777.817 |
| X4P-001 300 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 21 | 58118.02 cells*hour/μL | Standard Deviation 112851.505 |
| X4P-001 300/400 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 5 | 24175.00 cells*hour/μL | Standard Deviation 777.817 |
| X4P-001 300/400 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 13 | -2602.50 cells*hour/μL | — |
| X4P-001 300/400 mg | Mean Value of the Area Under the Plasma Concentration-time Curve for Absolute Neutrophil Count (AUCANC) | Week 21 | 58118.02 cells*hour/μL | Standard Deviation 112851.505 |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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'.
Time frame: From first dose of study drug through 10 days after the last dose of the study drug (Maximum exposure: 1712 days)
Population: The Safety Population included all participants who received at least 1 dose of the study medication (mavorixafor). Data for this Outcome Measure were collected by dose level; therefore, participants may have been included in more than one arm (dose level).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| X4P-001 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| X4P-001 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| X4P-001 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| X4P-001 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| X4P-001 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
| X4P-001 400 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| X4P-001 300/400 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 7 Participants |