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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03995108
Ethics application status
Date submitted
19/06/2019
Date registered
21/06/2019
Date last updated
7/05/2021

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 Period. Adolescents weighing =50 kg will receive mavorixafor 200 mg QD. Participants who complete the Randomized 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 Period. Participants who complete the Randomized 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 Period: Time (in Hours) Above Absolute Neutrophil Count (ANC) Threshold of 500 Cells/Microliter (µL)
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 Period: Area Under the Curve for ANC (AUCANC) Using Trapezoidal Method
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 Period: Infection Rate (Percentage of Participants With Infections) Based on Infections Adjudicated by a Blinded, Independent AC
Timepoint [2] 0 0
Baseline up to Week 52
Secondary outcome [3] 0 0
Randomized 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 [3] 0 0
Week 52
Secondary outcome [4] 0 0
Randomized 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 [4] 0 0
Week 52
Secondary outcome [5] 0 0
Randomized Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Dermatologist Clinical Global Impression of Change (CGI-C)
Timepoint [5] 0 0
Baseline, Week 52
Secondary outcome [6] 0 0
Randomized Period: Time to Early Release as Confirmed by Blinded Independent AC
Timepoint [6] 0 0
Baseline up to Week 52
Secondary outcome [7] 0 0
Randomized Period: Percentage of Neutrophil Responders
Timepoint [7] 0 0
Baseline up to Week 52
Secondary outcome [8] 0 0
Randomized Period: Mavorixafor Treatment Group: AUCANC
Timepoint [8] 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 [9] 0 0
Randomized Period: Time (in Hours) Above Absolute Lymphocyte Count (ALC) Threshold of 1000 Cells/µL
Timepoint [9] 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 [10] 0 0
Randomized Period: Area Under the Curve for ALC (AUCALC)
Timepoint [10] 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 [11] 0 0
Randomized Period: Percentage of Lymphocyte Responders
Timepoint [11] 0 0
Baseline up to Week 52
Secondary outcome [12] 0 0
Change From Baseline in Total ALC, Absolute Monocyte Count (AMC), ANC, and White Blood Cell (WBC) at Week 52
Timepoint [12] 0 0
Baseline, Week 52
Secondary outcome [13] 0 0
Randomized Period: Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 52
Timepoint [13] 0 0
Baseline, Week 52
Secondary outcome [14] 0 0
Randomized Period: Infection Characteristics, The Number of Participants With Severe Infections
Timepoint [14] 0 0
Baseline up to Week 52
Secondary outcome [15] 0 0
Randomized Period: Infection Duration
Timepoint [15] 0 0
Baseline up to Week 52
Secondary outcome [16] 0 0
Randomized Period: Infection-Free Time
Timepoint [16] 0 0
Baseline up to Week 52
Secondary outcome [17] 0 0
Randomized Period: Number of Days Lost From Work/School
Timepoint [17] 0 0
Baseline up to Week 52
Secondary outcome [18] 0 0
Randomized Period: Quality of Life as Measured by 36-Item Short Form Survey Score
Timepoint [18] 0 0
Baseline up to Week 52
Secondary outcome [19] 0 0
Randomized Period: Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) Score
Timepoint [19] 0 0
Baseline up to Week 52
Secondary outcome [20] 0 0
Randomized 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 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 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 Period: Pharmacokinetics (PK), Maximum Observed Plasma Concentration (Cmax) of Mavorixafor
Timepoint [23] 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 [24] 0 0
Randomized Period: PK, Time to Reach Cmax (Tmax) of Mavorixafor
Timepoint [24] 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 [25] 0 0
Randomized Period: PK, Half-Life of (T1/2) of Mavorixafor
Timepoint [25] 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 [26] 0 0
Randomized Period: PK, Area Under the Curve (AUC) of Mavorixafor
Timepoint [26] 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 [27] 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 [27] 0 0
Year 1 of open-label period
Secondary outcome [28] 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 [28] 0 0
Year 1 of open-label period
Secondary outcome [29] 0 0
Open-Label Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Dermatologist CGI-C
Timepoint [29] 0 0
Baseline, Week 52 of open-label period
Secondary outcome [30] 0 0
Open-Label Period: Infection Rate (Percentage of Participants With Infections) Based on Infections Adjudicated by an AC
Timepoint [30] 0 0
Baseline up to Week 52 of open-label period

Eligibility
Key inclusion criteria
- 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
Gender
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.

Exclusion Criteria for the Open-Label Period:

- Participants who experience any treatment-limiting toxicity (TLT) will be excluded
from participating in the Open-Label Period.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Russian Federation
State/province [15] 0 0
Moscow
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Saint Pertersburg
Country [17] 0 0
Spain
State/province [17] 0 0
Esplugues De Llobregat
Country [18] 0 0
Spain
State/province [18] 0 0
Sevilla

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, placebo-controlled Randomized Period and an Open-Label
extension Period. The primary objective of the Randomized 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 extension Period, if regionally applicable, until
mavorixafor becomes commercially available, or until the study is terminated by the Sponsor.
Trial website
https://clinicaltrials.gov/show/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
X4 Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
857-529-5779
Fax 0 0
Email 0 0
patientinfo@x4pharma.com
Contact person for scientific queries

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