Health Condition 1: D80-D89- Certain disorders involving the immune mechanism
Conditions
Interventions
Intervention1: Mavorixafor: Oral tablet 100 mg each administered up to 400mg/day (up to 4 tablets) from Day 1 through Week 52
Control Intervention1: Placebo: Placebo matching to mavorixafor orally onc
Sponsors
Novotech Clinical Research India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. 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. 2. 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. Primary autoimmune neutropenia 3. 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. 4. 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). 5. 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. 6. 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. 7. 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. 8. Body weight of more than equal to 15 kg (inclusive). 9. Contraceptive use by men and women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 10. 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.
Exclusion criteria
Exclusion criteria: 1. Participant is incapacitated and unable to comply with protocol-specific requirements 2. 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. 3. 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. 4. 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. 5. Known active COVID-19 infection or a positive test within the local accepted clinical and governmental guidelines for a communicable window. 6. 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. 7. 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. 8. An active malignancy or history (less than equals to 5 years prior to enrollment in the study) of solid or hematologic malignancy. 9. 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. 10. Participants who are awaiting HSCT due to somatic variants in genes associated with high risk for clonal proliferation. 11. 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. 12. Receiving or requiring any medication or therapy that is prohibited. 13. Received more than 1 dose of mavorixafor in the past. 14. Received a CXCR4 antagonist (other than mavorixafor) in the pa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annualized infection rate based on infections adjudicated by a Blinded Infection Adjudication Committee (BIAC) during the 52-week treatment periodTimepoint: Baseline to Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 periodTimepoint: Baseline to Week 52;Infection severity based on CTCAE grading, adjudicated by a BIAC during the 52-week treatment periodTimepoint: Baseline to Week 52;Infection duration based on duration of infections adjudicated by a BIAC during the 52-week treatment periodTimepoint: Baseline to week 52;Antibiotic Use Due to Infection, Characterized by the Frequency of Antibiotic use during the 52-week teatment PeriodTimepoint: Baseline to week 52;Change from baseline to Week 52/Day 365 in PROMIS SF Fatigue Questionnaire total scoreTimepoint: Baseline to Week 52;Oral ulcers, as assessed by presence or absence of ulcers, during the 52-week treatment periodTimepoint: Baseline to Week 52 | — |
Countries
Argentina, Australia, Brazil, Canada, Colombia, Czech Republic, France, Georgia, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Malaysia, Portugal, Republic of Korea, Romania, Serbia, Spain, Switzerland, Thailand, Turkey, Ukraine, United Kingdom, United States of America
Contacts
Public ContactKanhaiya Choudhary
Novotech India Private Limited
Outcome results
None listed