CTRI/2025/02/080276Other (Terminated)3 期
A Phase 3 randomized double-blind placebo-controlled multicenter study of mavorixafor in participants with congenital and acquired primary autoimmune and idiopathic chronic neutropenic disorders who are experiencing recurrent and or serious infections
Novotech Clinical Research India Private Limited4 个研究点 分布在 1 个国家目标入组 150 人开始时间: 2025年2月25日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- Other (Terminated)
- 发起方
- 入组人数
- 150
- 试验地点
- 4
- 主要终点
- Annualized infection rate based on infections adjudicated by a Blinded Infection Adjudication Committee (BIAC) during the 52-week treatment period
研究概览
简要总结
The purpose of this study is to demonstrate the efficacy and evaluate the safety, and tolerability of mavorixafor in participants with congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorders who are experiencing recurrent and or serious infections as assessed by demonstrating its clinical benefit and increasing levels of circulating neutrophils.
All participants will continue their pre-study background therapy, defined as the participants current treatment regimen. Options include, but are not limited to granulocyte-colony stimulating factor, immunoglobulin replacement therapy, prophylactic antibiotics, or watchful waiting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 12.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Participants must be at least 12 years of age, at the time of signing the informed consent or assent, as per the local regulations and guidelines.
- •Diagnosis of congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorder more than or equals to 6 months prior to the screening visit that is NOT attributable to medications, active or recent infections or malignancy.
- ••Congenital Neutropenia, including but not limited to these classifications: a.
- •Isolated with a permanent (non-cyclic) presentation, example, ELANE, CSF3R, CXCR2, WAS b.
- •Associated with extra hematological manifestations, example, Barth syndrome, Cohen syndrome, G6PC3, Kostmann disease c.
- •Associated with metabolic disorders, example, glycogen storage disease 1b (GSD1b) d.
- •Shwachman-Diamond syndrome •Acquired Primary Neutropenia a.
- •Chronic idiopathic neutropenia b.
- •Have a confirmed trough ANC less than 1500 cells per microliter during the screening visit (single ANC measurement) and at baseline visit (mean ANC over 6 hours) held at least 2 weeks prior to Day 1 dosing, with no clinical evidence of systemic infection.
- •Prior history of recurrent and or serious infections during the 12 months preceding the screening visit (suffering sequelae of CN), as defined by having at least 2 infections in the last 12 months that meet at least 1 of the following criteria: Infection requiring the use of antibiotics (intravenous or oral or topical) Infection requiring a visit to healthcare facility (including but not limited to emergency room visit, urgent care facility, primary care physicians office, or inpatient hospitalization).
- •Participants who are on G-CSF or other active background therapy must have been receiving these therapies during the previous 12 months while continuing to suffer from infections, be on a stable dose and dosing schedule for more than equal to 4 weeks prior to screening visit and remain on this dose and dosing schedule throughout the study.
- •Participants must be willing to keep their G-CSF or other background therapy doses per regimens stable (other than for safety reasons) for the duration of the study.
- •Bone marrow aspirate with minus–plus without biopsy during the screening visit (or prior documentation of bone marrow aspirate minus–plus biopsy within previous 9 months submitted for review and considered adequate for type of CN by central review hematopathologist) does not demonstrate evidence of hematological malignancy or high risk for transformation by central review hematopathologist.
- •Body weight of more than equal to 15 kg (inclusive).
- •Contraceptive use by men and women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Participant, parent, and or appropriate legally designated representative is capable of giving signed ICF and or assent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
排除标准
- •Participant is incapacitated and unable to comply with protocol-specific requirements
- •A diagnosis of secondary neutropenia including those due to: a.
- •Hypersplenism b.
- •Infection c.
- •Malignancy d.
- •Autoimmune disease, Example, systemic lupus erythematosus, rheumatoid arthritis, irritable bowel disease, graft-versus-host disease, thyroid disease e.
- •Nutritional deficiency, Example, vitamin B12, folic acid, copper, caloric malnutrition f.
- •Drug-induced cause, Example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies.
- •A diagnosis of any of the following: • Aplastic anemia • WHIM syndrome • Certain CNs, including but not limited to these classifications, are excluded: a.
- •Isolated with a cyclic presentation, example, ELANE b.
- •Associated with immune dysregulation, example, CVID, ALPS, familial hemophagocytic lymphohistiocytosis, Chediak-Higashi syndrome, GATA2 deficiency syndrome c.
- •Associated with bone marrow failure, example, Fanconi anemia, Diamond-Blackfan anemia.
- •Neutropenia associated with a Duffy-null phenotype (formerly known as benign ethnic neutropenia).
- •However, a participant with an autosomal dominant pathogenic variant in a gene associated with CN on a Duffy-null background may be eligible for inclusion.
- •A history of HIV and an acquired immunodeficiency syndrome-defining condition other than CD4 plus count less than 200 cells per microliter.
- •Participants with HIV may be enrolled if viral load as determined by routinely used tests has been undetectable for at least 6 months prior to the screening visit; if the participant is taking effective antiretroviral therapy (ART), regimen must have been stable for more than 4 weeks prior to the screening visit.
- •Known active COVID-19 infection or a positive test within the local accepted clinical and governmental guidelines for a communicable window.
- •Major surgery less than equal to 6 weeks before the baseline visit requiring general anesthesia or which, in the opinion of the Investigator, may compromise the safety of the participant.
- •A medical or personal condition that may potentially compromise the safety of the participant, may preclude the participants successful completion of the clinical study, or could, in the opinion of the Investigator or the Sponsor, interfere with the objectives of the study.
- •An active malignancy or history (less than equals to 5 years prior to enrollment in the study) of solid or hematologic malignancy.
- •Exception: Adequately treated basal cell or squamous cell skin cancer, localized prostate cancer, carcinoma in situ of the cervix, or in situ ductal or lobular carcinoma of the breast.
- •Participants who are awaiting HSCT due to somatic variants in genes associated with high risk for clonal proliferation.
- •Diagnosed or suspected congenital long QT syndrome or any history of clinically significant (CS) ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes).
- •Any history of arrhythmia will be discussed with the Sponsors Medical Monitor before the participants entry into the study.
- •Receiving or requiring any medication or therapy that is prohibited.
- •Received more than 1 dose of mavorixafor in the past.
- •Received a CXCR4 antagonist (other than mavorixafor) in the past 6 months.
- •Participants taking pegylated-G-CSF unless they have a diagnosis of congenital neutropenia confirmed at the screening visit.
- •Unless otherwise indicated by the Medical Monitor following review, drugs which are highly dependent on CYP2D6 for clearance are prohibited for a period starting 14 days or 5 half-lives, whichever is longer, prior to administration of mavorixafor and during the study.
- •Systemic glucocorticoids (more than 5 mg prednisone equivalent per day) are prohibited for a period starting 14 days or 5 half-lives, whichever is longer, prior to administration of mavorixafor and during the study.
- •Grapefruit-containing products, which are variable inhibitors of CYP3A4, are prohibited for a period starting 5 days prior to administration of mavorixafor and during the study.
- •St. Johns wort, which is an inducer of CYP3A4, is prohibited for a period starting 7 days prior to administration of mavorixafor and during the study.
- •Positive hepatitis C virus (HCV) antibodies with confirmation by HCV ribonucleic acid polymerase chain reaction reflex testing.
- •Positive hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb).
- •If the participant tests HbsAg negative, HbcAb positive, and hepatitis B surface antibody positive upon reflex testing, the participant would be considered eligible.
- •Laboratory test results meeting more than equal to 1 of the following criteria at the screening visit: • Hemoglobin less than 9.0 g per dL • Platelets less than 30,000 per microliter • Estimated glomerular filtration rate less than 30 mL per min per 1.73 m2, as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation • Serum aspartate transaminase more than 2.5 times upper limit of normal (ULN) • Serum alanine transaminase more than 2.5 times ULN • Total bilirubin more than 1.5 times ULN (unless due to Gilberts syndrome, in which case total bilirubin more than equal to 3.0 times ULN and direct bilirubin more than 1.5 times ULN)
- •Prolonged corrected QT interval more than 450 ms using Fridericias formula at the screening visit.
- •Participant is currently taking or has taken an investigational drug less than 30 days prior to the screening visit.
- •Participant is pregnant or breastfeeding.
- •Unable and or unwilling to swallow capsules.
- •Known systemic hypersensitivity to the mavorixafor drug substance, its inactive ingredients, or the place.
结局指标
主要结局
Annualized infection rate based on infections adjudicated by a Blinded Infection Adjudication Committee (BIAC) during the 52-week treatment period
时间窗: Baseline to Week 52
次要结局
- Proportion of ANC responders. An ANC responder is a participant meeting the definition of a positive ANC(response at least 3 out of 6 visits [Weeks 4, 8, 13,26, 39, and 52] during the 52-week treatment period)
- Infection severity based on CTCAE grading, adjudicated by a(BIAC during the 52-week treatment period)
- Infection duration based on duration of infections adjudicated by a BIAC during the 52-week treatment period(Baseline to week 52)
- Antibiotic Use Due to Infection, Characterized by the Frequency of Antibiotic use during the 52-week teatment Period(Baseline to week 52)
- Change from baseline to Week 52/Day 365 in PROMIS SF Fatigue Questionnaire total score(Baseline to Week 52)
- Oral ulcers, as assessed by presence or absence of ulcers, during the 52-week treatment period(Baseline to Week 52)
研究者
Dr Alok Ranjan
Assistant Professor
研究点 (4)
Loading locations...
相似试验
尚未招募
3 期
A Phase 3 Trial of JKN2401 Injection in COPDNCT07330310Joincare Pharmaceutical Group Industry Co., Ltd888
尚未招募
不适用
A Clinical Study to Assess the Safety and Efficacy of Scalp Cream in patients with DandruffCTRI/2025/07/090946Blossom Microbiotics LLC34
招募中
2 期
Study to Assess Efficacy and Safety of HSK39297 Tablets in Patients With LNNCT07363460Haisco Pharmaceutical Group Co., Ltd.105
进行中（未招募）
2 期
A Study to Evaluate the Efficacy, Safety, and Tolerability of ASC30 Tablets in Participants With Type 2 Diabetes MellitusNCT07321678Ascletis Pharma (China) Co., Limited100
招募中
2 期
Efficacy and Safety of GL0034 in Overweight or Obese Adults With Type II Diabetes MellitusNCT07282743Sun Pharmaceutical Industries Limited285