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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03995108




Registration number
NCT03995108
Ethics application status
Date submitted
19/06/2019
Date registered
21/06/2019
Date last updated
30/08/2024

Titles & IDs
Public title
Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Mavorixafor in Patients With WHIM Syndrome With Open-Label Extension
Secondary ID [1] 0 0
2019-001153-10
Secondary ID [2] 0 0
X4P-001-103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
WHIM Syndrome 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mavorixafor
Treatment: Drugs - Placebo

Experimental: Mavorixafor - Participants (adults and adolescents \[12 to 17 years of age weighing \>50 kilograms \[kg\]) will receive mavorixafor 400 milligrams (mg) once daily (QD) orally for 52 weeks in the Randomized Placebo-Controlled Period. Adolescents weighing =50 kg will receive mavorixafor 200 mg QD. Participants who complete the Randomized Placebo-Controlled 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 QD orally for 52 weeks in the Randomized Placebo-Controlled Period. Participants who complete the Randomized Placebo-Controlled 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.


Treatment: Drugs: Mavorixafor
Mavorixafor provided as 100 mg capsules.

Treatment: Drugs: Placebo
Placebo matching to mavorixafor capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Randomized Placebo-Controlled Period: Time (in Hours) Above Threshold-Absolute Neutrophil Count (TAT-ANC in hours) of = 500 Cells/Microliter (µL) over a 24-hour period
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Open-Label Period: Percentage of Participants With Adverse Events (AEs)
Timepoint [2] 0 0
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 outcome [1] 0 0
Randomized Placebo-Controlled Period: Time (in Hours) Above Threshold-Absolute Lymphocyte Count (TAT-ALC) of = 1000 Cells/µL over a 24-hour period
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Randomized Placebo-Controlled Period: Composite Clinical Efficacy for Mavorixafor based on total infection score and total wart change score
Timepoint [2] 0 0
Baseline up to Week 52
Secondary outcome [3] 0 0
Randomized Placebo-Controlled Period: Change From Baseline in Total Warts Score at Week 52
Timepoint [3] 0 0
Baseline, Week 52
Secondary outcome [4] 0 0
Randomized Placebo-Controlled Period: Total Infection Score for Mavorixafor
Timepoint [4] 0 0
Baseline up to Week 52
Secondary outcome [5] 0 0
Randomized Placebo-Controlled Period: Time to Early Release
Timepoint [5] 0 0
Baseline up to Week 52
Secondary outcome [6] 0 0
Randomized Placebo-Controlled Period: TAT-ALC of = 1000 Cells/µL in Participants With Lymphopenia
Timepoint [6] 0 0
Baseline
Secondary outcome [7] 0 0
Randomized Placebo-Controlled Period: Total Infection Score for Participants With Non-Immunoglobulin (non-Ig) Use (Percentage of Participants With Infections)
Timepoint [7] 0 0
Baseline up to Week 52
Secondary outcome [8] 0 0
Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline, Based on Clinical Global Impression of Change (CGI-C)
Timepoint [8] 0 0
Baseline
Secondary outcome [9] 0 0
Randomized Placebo-Controlled Period: Composite Clinical Efficacy (Total Infection Score and Total Wart Change Score) for Participants With Non-Ig Use
Timepoint [9] 0 0
Baseline up to Week 52
Secondary outcome [10] 0 0
Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline (CGI-C), Based on Local Dermatologist Review
Timepoint [10] 0 0
Baseline
Secondary outcome [11] 0 0
Randomized Placebo-Controlled Period: Participant Global Impression of Change (PGI-C)
Timepoint [11] 0 0
Baseline up to Week 52
Secondary outcome [12] 0 0
Randomized Placebo-Controlled Period: Participant Global Impression of Severity (PGI-S)
Timepoint [12] 0 0
Baseline up to Week 52
Secondary outcome [13] 0 0
Randomized Placebo-Controlled Period: Vaccine Titer Levels at Week 52 in Participants Vaccinated at Week 13, With Tetanus, Diphtheria, and Pertussis (Tdap) Including Pertussis Toxin, and Tetanus
Timepoint [13] 0 0
Week 52
Secondary outcome [14] 0 0
Randomized Placebo-Controlled Period: Vaccine Titer Levels at Week 52 for Human Papillomavirus (HPV) 16 and HPV 18 in Participants Receiving Vaccinations With HPV 9-Valent Vaccine, Recombinant (Gardasil®9)
Timepoint [14] 0 0
Week 52
Secondary outcome [15] 0 0
Randomized Placebo-Controlled Period: Change From Baseline in Clinical Global Impression of Severity (CGI-S), Based on Local Dermatologist Review
Timepoint [15] 0 0
Baseline up to Week 52
Secondary outcome [16] 0 0
Randomized Placebo-Controlled Period: Number of Participants with Infections
Timepoint [16] 0 0
Baseline up to Week 52
Secondary outcome [17] 0 0
Randomized Placebo-Controlled Period: Infection-Free Time
Timepoint [17] 0 0
Baseline up to Week 52
Secondary outcome [18] 0 0
Randomized Placebo-Controlled Period: Number of Days Lost From Work/School
Timepoint [18] 0 0
Baseline up to Week 52
Secondary outcome [19] 0 0
Randomized Placebo-Controlled Period: Quality of Life as Measured by 36-Item Short Form Survey Score
Timepoint [19] 0 0
Baseline up to Week 52
Secondary outcome [20] 0 0
Randomized Placebo-Controlled Period: Quality of Life as Measured by EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score
Timepoint [20] 0 0
Baseline up to Week 52
Secondary outcome [21] 0 0
Randomized Placebo-Controlled Period: Quality of Life as Measured by Life Quality Index (LQI) Score
Timepoint [21] 0 0
Baseline up to Week 52
Secondary outcome [22] 0 0
Randomized Placebo-Controlled Period: Quality of Life as Measured by Dermatology LQI Score
Timepoint [22] 0 0
Baseline up to Week 52
Secondary outcome [23] 0 0
Randomized Placebo-Controlled Period: Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) Score
Timepoint [23] 0 0
Baseline up to Week 52
Secondary outcome [24] 0 0
Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on Dermatologist CGI-C Assessment
Timepoint [24] 0 0
Baseline to Week 52
Secondary outcome [25] 0 0
Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on AG Wart Severity Assessment
Timepoint [25] 0 0
Baseline to Week 52
Secondary outcome [26] 0 0
Randomized Placebo-Controlled Period: Number of Events Requiring Rescue Treatment Due to Infection
Timepoint [26] 0 0
Baseline to Week 52
Secondary outcome [27] 0 0
Randomized Placebo-Controlled Period: Number of Participants With Incidence and Duration of Hospitalizations Due to Infection
Timepoint [27] 0 0
Baseline to Week 52
Secondary outcome [28] 0 0
Randomized Placebo-Controlled Period: Number of Participants With Incidence of Newly Developed Warts
Timepoint [28] 0 0
Baseline to Week 52
Secondary outcome [29] 0 0
Randomized Placebo-Controlled Period: Area Under the Curve for ANC (AUCANC) Using Trapezoidal Method
Timepoint [29] 0 0
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
Secondary outcome [30] 0 0
Randomized Placebo-Controlled Period: Percentage of Neutrophil Responders
Timepoint [30] 0 0
Baseline up to Week 52
Secondary outcome [31] 0 0
Randomized Placebo-Controlled Period: Mavorixafor Treatment Group: AUCANC
Timepoint [31] 0 0
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
Secondary outcome [32] 0 0
Randomized Placebo-Controlled Period: Area Under the Curve for ALC (AUCALC)
Timepoint [32] 0 0
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
Secondary outcome [33] 0 0
Randomized Placebo-Controlled Period: Percentage of Lymphocyte Responders
Timepoint [33] 0 0
Baseline up to Week 52
Secondary outcome [34] 0 0
Randomized Placebo-Controlled Period: Change From Baseline in Total ALC, Absolute Monocyte Count (AMC), ANC, and White Blood Cell (WBC) at Week 52
Timepoint [34] 0 0
Baseline, Week 52
Secondary outcome [35] 0 0
Absolute and Fold Change From Baseline in Absolute T, B and Natural Killer Lymphocyte at Week 52
Timepoint [35] 0 0
Baseline, Week 52
Secondary outcome [36] 0 0
Randomized Placebo-Controlled Period: Number of Participants With AEs
Timepoint [36] 0 0
Baseline up to Week 52
Secondary outcome [37] 0 0
Randomized Placebo-Controlled Period: Pharmacokinetics (PK), Maximum Observed Plasma Concentration (Cmax) of Mavorixafor
Timepoint [37] 0 0
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
Secondary outcome [38] 0 0
Randomized Placebo-Controlled Period: PK, Time to Reach Cmax (Tmax) of Mavorixafor
Timepoint [38] 0 0
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
Secondary outcome [39] 0 0
Randomized Placebo-Controlled Period: PK, Half-Life of (T1/2) of Mavorixafor
Timepoint [39] 0 0
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
Secondary outcome [40] 0 0
Randomized Placebo-Controlled Period: PK, Area Under the Curve (AUC) of Mavorixafor
Timepoint [40] 0 0
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
Secondary outcome [41] 0 0
Open-Label Period: Percentage of Neutrophil Responders
Timepoint [41] 0 0
Baseline up to Week 52 of open-label period
Secondary outcome [42] 0 0
Open-Label Period: Percentage of Lymphocyte Responders
Timepoint [42] 0 0
Baseline up to Week 52 of open-label period
Secondary outcome [43] 0 0
Open-Label Period: Absolute and Fold Change From Baseline in Total ALC, AMC, ANC, and WBC at Week 52
Timepoint [43] 0 0
Baseline up to Week 52 of open-label period
Secondary outcome [44] 0 0
Open-Label Period: Vaccine Titer Levels During the First Year of Open-Label Period, in Participants Vaccinated With Tdap During the Study Including Pertusis Toxin and Tetanus
Timepoint [44] 0 0
Year 1 of open-label period
Secondary outcome [45] 0 0
Open-Label Period: Vaccine Titer Levels During the First Year of the Open-Label Period for HPV 16 and HPV 18 in Participants Receiving Vaccinations With HPV 9-Valent Vaccine, Recombinant (Gardasil®9) During the Study
Timepoint [45] 0 0
Year 1 of open-label period
Secondary outcome [46] 0 0
Open-Label Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Central Review of CGI-C
Timepoint [46] 0 0
Baseline, Week 52 of open-label period
Secondary outcome [47] 0 0
Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Central Review of CGI-S
Timepoint [47] 0 0
Baseline, Week 52 of open-label period
Secondary outcome [48] 0 0
Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-C
Timepoint [48] 0 0
Baseline, Week 52 of open-label period
Secondary outcome [49] 0 0
Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-S
Timepoint [49] 0 0
Baseline, Week 52 of open-label period
Secondary outcome [50] 0 0
Open-Label Period: Change Over Time in PGI-C
Timepoint [50] 0 0
Baseline up to Week 52 of open-label period
Secondary outcome [51] 0 0
Open-Label Period: Change Over Time in PGI-S
Timepoint [51] 0 0
Baseline up to Week 52 of open-label period
Secondary outcome [52] 0 0
Open-Label Period: Total Infection Score (Percentage of Participants With Infections)
Timepoint [52] 0 0
Baseline up to Week 52 of open-label period

Eligibility
Key inclusion criteria
Inclusion Criteria for the Randomized Placebo-Controlled Period :

* 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, obtained while participant has no clinical evidence of infection.

Inclusion Criteria for the Open-Label Period:

* Completed the Randomized Period; or
* Granted Early Release from the Randomized Period.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has known systemic hypersensitivity to the mavorixafor drug substance, its inactive ingredients, or the placebo.
* Is pregnant or breastfeeding.
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
31
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Wesley Hospital - Auchenflower
Recruitment hospital [2] 0 0
Children's Health Queensland Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Auchenflower
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
Austria
State/province [6] 0 0
Wien
Country [7] 0 0
Denmark
State/province [7] 0 0
Aarhus
Country [8] 0 0
France
State/province [8] 0 0
Rhne
Country [9] 0 0
France
State/province [9] 0 0
Paris Cedex 12
Country [10] 0 0
France
State/province [10] 0 0
Paris
Country [11] 0 0
Hungary
State/province [11] 0 0
Hajdu-Bihar
Country [12] 0 0
Israel
State/province [12] 0 0
Afula
Country [13] 0 0
Italy
State/province [13] 0 0
Piazza Del Mercato
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Netherlands
State/province [15] 0 0
Amsterdam
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Moscow
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Saint Pertersburg
Country [18] 0 0
Spain
State/province [18] 0 0
Esplugues De Llobregat
Country [19] 0 0
Spain
State/province [19] 0 0
Sevilla
Country [20] 0 0
Turkey
State/province [20] 0 0
Adana

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
X4 Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study has a double-blind, Randomized Placebo-Controlled Period and an Open-Label Period. The primary objective of the Randomized Placebo-Controlled 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 Period, if regionally applicable, until mavorixafor becomes commercially available, or until the study is terminated by the Sponsor.
Trial website
https://clinicaltrials.gov/study/NCT03995108
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Chief Medical Officer
Address 0 0
X4 Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03995108