WHIM Syndrome
Conditions
Interventions
Product Name: Mavorixafor
Product Code: X4P-001
Pharmaceutical Form: Capsule
INN or Proposed INN: Mavorixafor
CAS Number: 558447-26-0
Current Sponsor code: X4P-001
Concentration unit: mg milligram(s)
Sponsors
X4 Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for Randomized Period: 1. Be at least 12 years of age. 2. Have signed the current approved ICF. 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. 3. Have a genotype-confirmed mutation of CXCR4 consistent with WHIM phenotype. 4. Agree to use a highly effective form of contraception. 5. Be willing and able to comply with this protocol. 6. Have a confirmed ANC =400 cells/µL during screening, obtained while patient has no clinical evidence of infection. For ANC count >400 cells/µL due to an ongoing infection, patient may be allow to rescreen after the infection is determined by the treating physician to be cleared. The Medical Monitor should be notified and approve each rescreen occurrence. Inclusion criteria for Open-Label Period: 1. Completed the Randomized Placebo-Controlled Period. 2. Granted Early Release from the Randomized Placebo-Controlled Period. 3.Blind broken. Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 14 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: Exclusion criteria for Randomized Period: 1. Has known systemic hypersensitivity to the mavorixafor drug substance, its inactive ingredients, or the placebo. 2. Is pregnant or breastfeeding. 3. Has a known history of a positive serology or viral load for human immunodeficiency virus or a known history of AIDS. 4. Has, at screening, laboratory tests meeting 1 or more of the following criteria: - A positive hepatitis C virus antibody (HCVAb) with confirmation by hepatitis C virus ribonucleic acid polymerase chain reaction reflex testing. - A positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). - NOTE: if a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if the participant tests positive for hepatitis B surface antibody (also referred to as anti-HBsAg) on reflex testing. 5. Has, at screening, safety laboratory tests meeting 1 or more of the following criteria: - Hemoglobin 2.5x the upper limit of normal (ULN) - Serum alanine aminotransferase >2.5x ULN - Total bilirubin >1.5x ULN (unless due to Gilbert’s syndrome, in which case total bilirubin =3.0x ULN and direct bilirubin >1.5x ULN) 6. Had surgery requiring general anesthesia within the 4 weeks prior to Day 1. 7. Received any of the following treatments: - Plerixafor within 6 months prior to Day 1. - Chronic or prophylactic use of antibiotics (systemic or inhaled) within 4 weeks prior to Day 1. - Chronic or prophylactic use of G-CSF or granulocyte macrophage-colony stimulating factor within 2 weeks of Day 1. -Chronic or prophylactic use of systemic glucocorticoid use (>5 mg prednisone equivalent per day) within 2 weeks prior to Day 1. - Any investigational therapy within 5 half-lives or 2 weeks prior to Day 1, whichever is longer. Prior use of any investigational therapies must be discussed with the Medical Monitor. 8. Is currently taking or has, within 2 weeks prior to Day 1, received any medication that is prohibited, based on potential for drug-drug interactions. 9. Has, at the planned initiation of study drug, a clinically diagnosed active infection (excluding warts), that has the potential to raise the ANC counts. 10. Has had a total splenectomy within 1 year. 11. Has a current diagnosis of myelofibrosis. 12. Has a medical history of hematological malignancies. 13. Has any other 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. 14. Has corrected QT interval using Friedericia`s formula of > 450ms. Note: Central results should be used for determination of screening laboratory values when possible. However, local laboratory analysis may be used if central laboratories are not available, or for unscheduled visits, repeated samples, or in place of central laboratory samples that could not be processed or were out of window.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective for Randomized Period: To demonstrate the efficacy of mavorixafor in participants with Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome as assessed by increasing levels of circulating neutrophils compared with placebo, and relative to a clinically meaningful threshold. Primary Objective for Open-Label Period. To evaluate the long-term safety and tolerability of mavorixafor in participants with WHIM syndrome. ;Secondary Objective: Secondary Objective for Randomized Period: 1. To demonstrate the efficacy of mavorixafor in participants with WHIM syndrome as assessed by increasing levels of circulating lymphocytes compared with placebo and relative to a clinically meaningful threshold. 2. To demonstrate the clinical efficacy of mavorixafor in participants with WHIM syndrome as assessed by a composite endpoint of infections and warts. 3. To demonstrate the efficacy of mavorixafor in participants with WHIM syndrome as assessed by improvement in warts. 4. To demonstrate the efficacy of mavorixafor in participants with WHIM syndrome as assessed by reduction in infections. Secondary Objective for Open-Label Period: To evaluate the long-term efficacy of mavorixafor in participants with WHIM syndrome.;Primary end point(s): Primary endpoint in Randomized Period: Time above threshold-absolute neutrophil count (TAT-ANC; in hours) of = 500 cells/µL over a 24-hour period, assessed 4 times throughout the study (every 3 months for 12 months) for the Intent-to-Treat (ITT) Population. Primary Endpoint in Open-Label Period: Safety and tolerability of mavorixafor in participants with WHIM syndrome, as assessed by adverse events (AEs), clinical laboratory evaluations, vital signs,electrocardiogram (ECG), and physical and ophthalmologic examinations.;Timepoint(s) of evaluation of this end point: The primary endpoint analysis will compare the difference between mavorixafor and placebo with respect to the mean time above ANC thr | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints for Randomized period are: 1. Time above threshold-absolute lymphocyte count (TAT-ALC) of = 1000 cells/µL over a 24-hour period assessed 4 times throughout the study (every 3 months for 12 months) in the ITT Population. 2. Composite Clinical Efficacy Endpoint for mavorixafor based on total infection score and total wart change score in the ITT Population. 3. Total wart change score for mavorixafor based on central blinded, independent review of 3 target skin regions in the ITT Population. 4. Total infection score for mavorixafor based on number and severity of infections adjudicated by a blinded, independent Adjudication Committee (AC) in the ITT Population. Some of other secondary endpoints are: 1. Time to Early Release as confirmed by blinded independent AC in the ITT Population. 2. TAT-ALC of = 1000 cells/µL in participants with lymphopenia at baseline. 3. Composite endpoint based on total infection score and total wart change score for participants with warts at baseline or participants with non-Ig use. 4. Total infection score based on infections adjudicated by a blinded, independent AC for participants with non-Ig use. 5. Total wart change score (Clinical Global Impression of Change [CGIC]) based on blinded central review of 3 target skin regions for participants with warts at baseline. 6. Total wart change score (CGI-C) based on local dermatologist review of all regions for participants with warts at baseline. 7. Patient Global Impression of Change (PGI-C) from baseline. 8. Patient Global Impression of Severity (PGI-S) during treatment. 9. Vaccine titer levels at Week 52 in the Randomized Placebo-Controlled Period in all participants vaccinated at Week 13 with tetanus, diphtheria, and pertussis vaccine (Tdap), including pertussis toxin and tetanus. 10. Vaccine titer levels at Week 52 in the Randomized Placebo- Controlled Period for human papillomavirus (HPV) 16 and HPV 18 in all participants receiving vacci | — |
Countries
Australia, Austria, Denmark, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactMichael Tillinger
X4 Pharmaceuticals Incorporated
Outcome results
None listed