2024-518461-10-00招募中3 期
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Mavorixafor in Patients with WHIM Syndrome with Open-Label Extension
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Randomized Placebo-Controlled 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.
研究概览
简要总结
-Randomized Placebo-Controlled 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. -Open label period: To evaluate the long-term safety and tolerability of mavorixafor in participants with WHIM syndrome
入排标准
- 年龄范围
- 0 years 至 65+ years（0-17 Years, 18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for Randomized Period:
- •Be at least 12 years of age.
- •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 CXCR4 consistent with WHIM phenotype.
- •Agree to use a highly effective form of contraception, as detailed in Section 5.3.
- •Be willing and able to comply with this protocol.
- •Have a confirmed ANC ≤ 400 cells/μL during screening, obtained while participant has no clinical evidence of infection.
- •Inclusion criteria for Open-Label Period:
- •Completed the Randomized Placebo-Controlled Period.
- •Granted Early Release from the Randomized Placebo-Controlled Period.
- •Blind broken.
排除标准
- •Exclusion criteria for Randomized Period:
- •Has known systemic hypersensitivity to the mavorixafor drug substance, its inactive ingredients, or the placebo.
- •Is pregnant or breastfeeding.
- •Has a known history of a positive serology or viral load for HIV or a known history of AIDS.
- •Has, at screening, laboratory tests meeting 1 or more of the following criteria: − A positive hepatitis C virus antibody 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.
- •Has, at screening, safety laboratory tests meeting 1 or more of the following criteria: − Hemoglobin < 8.0 g/dL − Platelets < 75,000 cells/μL − Estimated glomerular filtration rate based on the Modification of Diet in Renal Disease of ≤ 29 mL/min/1.73 m2 (Stage 4 or 5 chronic kidney disease) − Serum aspartate aminotransferase > 2.5 × ULN − Serum alanine aminotransferase > 2.5 × ULN − Total bilirubin > 1.5 × ULN (unless due to Gilbert’s syndrome, in which case total bilirubin ≥ 3.0 × ULN and direct bilirubin > 1.5 × ULN)
- •Had surgery requiring general anesthesia within the 4 weeks prior to Day
- •Received any of the following treatments: − Plerixafor within 6 months prior to Day
- •− Chronic or prophylactic use of antibiotics (systemic or inhaled) within 4 weeks prior to Day
- •− Chronic or prophylactic use of G-CSF or granulocyte macrophage-colony stimulating factor within 2 weeks of Day
- •− Chronic or prophylactic use of systemic glucocorticoid use (> 5 mg prednisone equivalent per day) within 2 weeks prior to Day
- •− 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.
- •Is currently taking or has, within 2 weeks prior to Day 1, received any medication that is prohibited (see Section 6.4.1), based on potential for drug-drug interactions.
- •Has, at the planned initiation of study drug, a clinically diagnosed active infection (excluding warts) that has the potential to raise the ANC counts.
- •Has had a total splenectomy within 1 year.
- •Has a current diagnosis of myelofibrosis.
- •Has a medical history of hematological malignancies.
- •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.
- •Has corrected QT interval using Fridericia’s formula of > 450 ms.
结局指标
主要结局
Randomized Placebo-Controlled 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.
Randomized Placebo-Controlled 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.
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) assessments, physical and ophthalmologic examinations.
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) assessments, physical and ophthalmologic examinations.
次要结局
- Randomized Placebo-Controlled Period: 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.
- Open-Label Period: 1. Proportion of neutrophil responders, defined as participants with ANC ≥ 500 cells/μL threshold. 2. Proportion of lymphocyte responders, defined as participants with baseline ALC below the lower limit of normal who achieve on-treatment ALC ≥ 1000 cells/μL threshold.
- 3. Absolute and fold change from baseline for total ALC, AMC, ANC, and WBC count. 4. Vaccine titer levels during the Open-Label Period in all participants vaccinated with Tdap) during the study, including pertussis toxin and tetanus.
- 5. Vaccine titer levels during the Open-Label Period for HPV 16 and HPV 18 in all participants receiving vaccinations with HPV 9-valent vaccine, recombinant (Gardasil®9) during the study. 6. Change from baseline in cutaneous warts, based on central review of CGI-C and CGI-S.
- 7. Change from baseline in cutaneous warts, based on local dermatologist review of CGI-C and CGI-S. 8. Change over time in PGI-S and PGI-C. 9. Total infection score as adjudicated by an independent AC.
- For the full list of endpoints please refer to the protocol.
研究者
Kathleen Galvez
Scientific
X4 Pharmaceuticals Inc.
研究点 (6)
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