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Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome

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ClinicalTrials.gov Identifier: NCT03995108
Recruitment Status : Recruiting
First Posted : June 21, 2019
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
X4 Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
WHIM Syndrome Drug: Mavorixafor Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Mavorixafor in Patients With WHIM Syndrome With Open-Label Extension
Actual Study Start Date : October 17, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Mavorixafor
Participants will receive mavorixafor 400 milligrams (mg) once daily 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 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.
Drug: Mavorixafor
Mavorixafor provided as four 100 mg capsules.
Other Name: AMD11070, X4P-001

Placebo Comparator: Placebo
Participants will receive placebo matching to mavorixafor once daily 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.
Drug: Mavorixafor
Mavorixafor provided as four 100 mg capsules.
Other Name: AMD11070, X4P-001

Drug: Placebo
Placebo matching to mavorixafor provided as four capsules.




Primary Outcome Measures :
  1. Randomized Period: Time (in Hours) Above Absolute Neutrophil Count (ANC) Threshold of 500 Cells/Microliter (µL) [ Time Frame: 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 ]
  2. Open-Label Period: Percentage of Participants With Adverse Events (AEs) [ Time Frame: 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 Measures :
  1. Randomized Period: Area Under the Curve for ANC (AUCANC) Using Trapezoidal Method [ Time Frame: 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 ]
  2. Randomized Period: Infection Rate (Percentage of Participants With Infections) Based on Infections Adjudicated by a Blinded, Independent AC [ Time Frame: Baseline up to Week 52 ]
  3. Randomized Period: Number of Proactive Vaccine Titers at Week 52 [ Time Frame: Week 52 ]
  4. Randomized Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Dermatologist Clinical Global Impression of Change [ Time Frame: Baseline, Week 52 ]
  5. Randomized Period: Percentage of Neutrophil Responders [ Time Frame: Baseline up to Week 52 ]
  6. Randomized Period: Mavorixafor Treatment Group: AUCANC [ Time Frame: 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 ]
  7. Randomized Period: Time (in Hours) Above Absolute Lymphocyte Count (ALC) Threshold of 1000 Cells/µL [ Time Frame: 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 ]
  8. Randomized Period: Area Under the Curve for ALC (AUCALC) [ Time Frame: 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 ]
  9. Randomized Period: Percentage of Lymphocyte Responders [ Time Frame: Baseline up to Week 52 ]
  10. Randomized Period: Duration of Infection [ Time Frame: Baseline up to Week 52 ]
  11. Randomized Period: Infection Characteristics, The Number of Participants With Severe Infections [ Time Frame: Baseline up to Week 52 ]
  12. Randomized Period: Infection-Free Time [ Time Frame: Baseline up to Week 52 ]
  13. Randomized Period: Number of Days Lost From Work/School [ Time Frame: Baseline up to Week 52 ]
  14. Randomized Period: Quality of Life as Measured by 36-Item Short Form Survey Score [ Time Frame: Baseline up to Week 52 ]
  15. Randomized Period: Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) Score [ Time Frame: Baseline up to Week 52 ]
  16. Randomized Period: Quality of Life as Measured by EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score [ Time Frame: Baseline up to Week 52 ]
  17. Randomized Period: Quality of Life as Measured by Life Quality Index (LQI) Score [ Time Frame: Baseline up to Week 52 ]
  18. Randomized Period: Quality of Life as Measured by Dermatology LQI Score [ Time Frame: Baseline up to Week 52 ]
  19. Randomized Period: Pharmacokinetics (PK), Maximum Observed Plasma Concentration (Cmax) of Mavorixafor [ Time Frame: 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 ]
  20. Randomized Period: PK, Time to Reach Cmax (Tmax) of Mavorixafor [ Time Frame: 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 ]
  21. Randomized Period: PK, Half-Life of (T1/2) of Mavorixafor [ Time Frame: 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 ]
  22. Randomized Period: PK, Area Under the Curve (AUC) of Mavorixafor [ Time Frame: 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 ]
  23. Open-Label Period: Number of Proactive Vaccine Titers at Week 13 [ Time Frame: Week 13 of open-label period ]
  24. Open-Label Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Dermatologist Clinical Global Impression of Change [ Time Frame: Baseline, Week 52 of open-label period ]
  25. Open-Label Period: Infection Rate (Percentage of Participants With Infections) Based on Infections Adjudicated by a Blinded, Independent AC [ Time Frame: Baseline up to Week 52 of open-label period ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be at least 12 years of age and Tanner stage greater than or equal to (≥) 3.
  • 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.

Inclusion Criteria for the Open-Label Period:

  • Completed the Randomized Period; or
  • Granted Early Release from the Randomized Period.

Exclusion Criteria:

  • Has known systemic hypersensitivity to the mavorixafor drug substance, its inactive ingredients, or the placebo.
  • Is pregnant or nursing.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03995108


Contacts
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Contact: X4 Pharmaceuticals 857-529-5779 patientinfo@x4pharma.com

Locations
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United States, California
University of California San Diego Health/Rady Children's Hospital Recruiting
San Diego, California, United States, 92123
Contact: Bob Geng, MD    858-966-5961    bgeng@ucsd.edu   
Contact: Diba Mortazavi    858-966-1700 ext 3422    dmortazavi@ucsd.edu   
California Dermatology Institute Recruiting
Thousand Oaks, California, United States, 91320
Contact: Shawn Ahoubim         
Contact    800-222-5803      
Principal Investigator: David Ezra, MD         
United States, Maryland
Johns Hopkins University Medical Center Recruiting
Baltimore, Maryland, United States, 21224
Contact: Antoine Azar, MD    410-550-2300    Antoine.Azar@jhmi.edu   
Contact: Dawn Borst, RN    410-550-2300    dschech2@jhmi.edu   
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-9020
Contact: Kathryn Dickerson, MD    214-645-8300    Kathryn.Dickerson@UTSouthwestern.edu   
Contact: Anna Winborn    214-456-8185    anna.winborn@childrens.com   
Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark, 8000
Contact: Henrik Hasle, MD    45-78-450000    henrik.hasle@skejby.rm.dk   
Contact: Karen Møller, RN    45-78-450000    karemoel@rm.dk   
Korea, Republic of
Seoul National University Hospital, Children's Hospital Recruiting
Seoul, Korea, Republic of, 03080
Contact: Hyoung J Kang, MD    82-2-2072-3304    kanghj@snu.ac.kr   
Contact: Kyung A Kim       edy-jang@hanmail.net   
Spain
Hospital Sant Joan de Deu Barcelona Recruiting
Barcelona, Esplugues De Llobregat, Spain, 8950
Contact: Laia Alsina, MD    34-93280-4000    lalsina@sjdhospitalbarcelona.org   
Contact: Patricia Mendez    34-93280-4000    pmendez@fsjd.org   
Sponsors and Collaborators
X4 Pharmaceuticals
Investigators
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Study Director: Chief Medical Officer X4 Pharmaceuticals
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Responsible Party: X4 Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03995108    
Other Study ID Numbers: X4P-001-103
2019-001153-10 ( EudraCT Number )
4WHIM ( Other Identifier: X4 Pharmaceuticals )
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Syndrome
Disease
Pathologic Processes