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Trial record 2 of 4 for:    mavorixafor

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03995108
Recruitment Status : Active, not recruiting
First Posted : June 21, 2019
Last Update Posted : September 14, 2022
Sponsor:
Information provided by (Responsible Party):
X4 Pharmaceuticals

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.

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 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Mavorixafor
Mavorixafor provided as 100 mg capsules.
Other Name: AMD11070, X4P-001

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.
Drug: Mavorixafor
Mavorixafor provided as 100 mg capsules.
Other Name: AMD11070, X4P-001

Drug: Placebo
Placebo matching to mavorixafor capsules




Primary Outcome Measures :
  1. 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 [ 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 Placebo-Controlled Period: Time (in Hours) Above Threshold-Absolute Lymphocyte Count (TAT-ALC) of ≥ 1000 Cells/µL over a 24-hour period [ 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 Placebo-Controlled Period: Composite Clinical Efficacy for Mavorixafor based on total infection score and total wart change score [ Time Frame: Baseline up to Week 52 ]
  3. Randomized Placebo-Controlled Period: Change From Baseline in Total Warts Score at Week 52 [ Time Frame: Baseline, Week 52 ]
  4. Randomized Placebo-Controlled Period: Total Infection Score for Mavorixafor [ Time Frame: Baseline up to Week 52 ]
  5. Randomized Placebo-Controlled Period: Time to Early Release [ Time Frame: Baseline up to Week 52 ]
  6. Randomized Placebo-Controlled Period: TAT-ALC of ≥ 1000 Cells/µL in Participants With Lymphopenia [ Time Frame: Baseline ]
  7. Randomized Placebo-Controlled Period: Total Infection Score for Participants With Non-Immunoglobulin (non-Ig) Use (Percentage of Participants With Infections) [ Time Frame: Baseline up to Week 52 ]
  8. Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline, Based on Clinical Global Impression of Change (CGI-C) [ Time Frame: Baseline ]
  9. Randomized Placebo-Controlled Period: Composite Clinical Efficacy (Total Infection Score and Total Wart Change Score) for Participants With Non-Ig Use [ Time Frame: Baseline up to Week 52 ]
    Composite clinical efficacy will be calculated using the total infection score and total wart change score for participants with warts at baseline or non-Ig use. It will be analyzed by a blinded, independent AC.

  10. Randomized Placebo-Controlled Period: Change in Total Wart Score at Baseline (CGI-C), Based on Local Dermatologist Review [ Time Frame: Baseline ]
  11. Randomized Placebo-Controlled Period: Participant Global Impression of Change (PGI-C) [ Time Frame: Baseline up to Week 52 ]
  12. Randomized Placebo-Controlled Period: Participant Global Impression of Severity (PGI-S) [ Time Frame: Baseline up to Week 52 ]
  13. 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 [ Time Frame: Week 52 ]
  14. 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) [ Time Frame: Week 52 ]
  15. Randomized Placebo-Controlled Period: Change From Baseline in Clinical Global Impression of Severity (CGI-S), Based on Local Dermatologist Review [ Time Frame: Baseline up to Week 52 ]
  16. Randomized Placebo-Controlled Period: Number of Participants with Infections [ Time Frame: Baseline up to Week 52 ]
  17. Randomized Placebo-Controlled Period: Infection-Free Time [ Time Frame: Baseline up to Week 52 ]
  18. Randomized Placebo-Controlled Period: Number of Days Lost From Work/School [ Time Frame: Baseline up to Week 52 ]
  19. Randomized Placebo-Controlled Period: Quality of Life as Measured by 36-Item Short Form Survey Score [ Time Frame: Baseline up to Week 52 ]
  20. Randomized Placebo-Controlled Period: Quality of Life as Measured by EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score [ Time Frame: Baseline up to Week 52 ]
  21. Randomized Placebo-Controlled Period: Quality of Life as Measured by Life Quality Index (LQI) Score [ Time Frame: Baseline up to Week 52 ]
  22. Randomized Placebo-Controlled Period: Quality of Life as Measured by Dermatology LQI Score [ Time Frame: Baseline up to Week 52 ]
  23. Randomized Placebo-Controlled Period: Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL) Score [ Time Frame: Baseline up to Week 52 ]
  24. Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on Dermatologist CGI-C Assessment [ Time Frame: Baseline to Week 52 ]
  25. Randomized Placebo-Controlled Period: Change From Baseline in Anogenital (AG) Warts Based on AG Wart Severity Assessment [ Time Frame: Baseline to Week 52 ]
  26. Randomized Placebo-Controlled Period: Number of Events Requiring Rescue Treatment Due to Infection [ Time Frame: Baseline to Week 52 ]
  27. Randomized Placebo-Controlled Period: Number of Participants With Incidence and Duration of Hospitalizations Due to Infection [ Time Frame: Baseline to Week 52 ]
  28. Randomized Placebo-Controlled Period: Number of Participants With Incidence of Newly Developed Warts [ Time Frame: Baseline to Week 52 ]
  29. Randomized Placebo-Controlled 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 ]
  30. Randomized Placebo-Controlled Period: Percentage of Neutrophil Responders [ Time Frame: Baseline up to Week 52 ]
  31. Randomized Placebo-Controlled 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 ]
  32. Randomized Placebo-Controlled 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 ]
  33. Randomized Placebo-Controlled Period: Percentage of Lymphocyte Responders [ Time Frame: Baseline up to Week 52 ]
  34. Randomized Placebo-Controlled Period: Change From Baseline in Total ALC, Absolute Monocyte Count (AMC), ANC, and White Blood Cell (WBC) at Week 52 [ Time Frame: Baseline, Week 52 ]
  35. Absolute and Fold Change From Baseline in Absolute T, B and Natural Killer Lymphocyte at Week 52 [ Time Frame: Baseline, Week 52 ]
  36. Randomized Placebo-Controlled Period: Number of Participants With AEs [ Time Frame: Baseline up to Week 52 ]
  37. Randomized Placebo-Controlled 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 ]
  38. Randomized Placebo-Controlled 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 ]
  39. Randomized Placebo-Controlled 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 ]
  40. Randomized Placebo-Controlled 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 ]
  41. Open-Label Period: Percentage of Neutrophil Responders [ Time Frame: Baseline up to Week 52 of open-label period ]
  42. Open-Label Period: Percentage of Lymphocyte Responders [ Time Frame: Baseline up to Week 52 of open-label period ]
  43. Open-Label Period: Absolute and Fold Change From Baseline in Total ALC, AMC, ANC, and WBC at Week 52 [ Time Frame: Baseline up to Week 52 of open-label period ]
  44. 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 [ Time Frame: Year 1 of open-label period ]
  45. 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 [ Time Frame: Year 1 of open-label period ]
  46. Open-Label Period: Change From Baseline in Cutaneous Warts at Week 52, Based on Central Review of CGI-C [ Time Frame: Baseline, Week 52 of open-label period ]
  47. Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Central Review of CGI-S [ Time Frame: Baseline, Week 52 of open-label period ]
  48. Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-C [ Time Frame: Baseline, Week 52 of open-label period ]
  49. Open-Label Period: Change From Baseline in Cutaneous Warts, Based on Local Dermatologist CGI-S [ Time Frame: Baseline, Week 52 of open-label period ]
  50. Open-Label Period: Change Over Time in PGI-C [ Time Frame: Baseline up to Week 52 of open-label period ]
  51. Open-Label Period: Change Over Time in PGI-S [ Time Frame: Baseline up to Week 52 of open-label period ]
  52. Open-Label Period: Total Infection Score (Percentage of Participants With Infections) [ 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 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.

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.

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


Locations
Show Show 23 study locations
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: September 14, 2022
Last Verified: September 2022

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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