Invasive Aspergillosis MedDRA version: 20.1 Level: PT Classification code 10051597 Term: Cerebral aspergillosis System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.1 Level: PT Classification code 10006473 Term: Bronchopulmonary aspergillosis System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: VL-2397 for Injection
Product Code: VL-2397
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: An INN has not
AS2102397-00
SVS-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical Form:
Sponsors
Vical Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion into the VL2397-201 study, participants must meet all of the following criteria: 1. Male or female (non-pregnant) participants, = age 18 years at the time of consent, and hospitalized at randomization; women of childbearing potential must have a negative serum pregnancy test during screening 2. New diagnosis of possible, probable, or proven pulmonary (or sinopulmonary) IA as defined by the 2008 EORTC/MSG criteria with at least one of the following host factors: ? Acute leukemia (AML or ALL) or other hematological condition (chronic leukemia, myelodysplastic syndrome, multiple myeloma, or aplastic anemia) with severe neutropenia temporally related to the onset of IA ? Allogeneic HCT recipient ? Hematological condition (acute or chronic leukemia, myelodysplastic syndrome, multiple myeloma, or aplastic anemia), lymphoma, solid organ transplant or autologous HCT recipient receiving immunosuppressive therapy. Note: Immunosuppressive therapy is recent use of corticosteroids (at a mean minimum dose of 0.3 mg/kg/day of prednisone or equivalent for > 3 weeks) or other immunosuppressants such as calcineurin inhibitors, TNF-a blockers, T-cell-specific monoclonal antibodies, or nucleoside analogs. 3. Able to provide informed consent and willing to comply with the study requirements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Potential participants will be excluded from the study if any of the following criteria are met: 1. Respiratory failure on mechanical ventilation 2. Refractory or relapsed leukemia unlikely to respond to reinduction chemotherapy (unless the participant is an allo-HCT recipient) 3. Severe neutropenia (absolute neutrophil count 10 days that is unlikely to recover during the study 4. Unlikely to survive 30 days after first dose of Study Drug due to graft failure, severe (grade 4) acute graft-versus-host disease (GvHD), refractory chronic GvHD, or other life-threatening condition 5. IA (proven or suspected) involving sites other than lungs and sinuses, including central nervous system (CNS), skin, or liver, and/or disseminated disease 6. Suspected or proven infection with Candida krusei 7. Systemic infection with a bacterial or viral pathogen that is not under control or cannot be treated, or systemic infection with a fungal pathogen other than Aspergillus. Note: Uncomplicated bacteremia, uncomplicated urinary tract infection, and CMV viremia without end organ disease are allowed. 8. Uncontrolled diabetes (given the inherent higher risk for mucormycosis), unless the diagnosis is proven or probable IA 9. Recent episode of acute IA not responding to treatment, chronic aspergillosis, aspergilloma in pre-existing cavity, or allergic aspergillosis 10. Receipt of > 4 cumulative days of systemic antifungal treatment for IA within 7 days prior to study entry. Note: Recent or prior use of a mold-active antifungal for prophylaxis, as determined by the Investigator, is allowed. 11. Hepatic dysfunction, defined as any one of the following: total bilirubin = 3 x the upper limit of normal (ULN), alanine transaminase (ALT) or aspartate transaminase (AST) = 5 x ULN, cirrhosis, or chronic hepatic failure 12. Moderate to severe renal dysfunction defined as any one of the following: creatinine clearance < 50 mL/min at screening, currently on dialysis, or likely to require dialysis during administration of Study Drug 13. Treatment with any investigational drug in a clinical trial within 14 days prior to the first dose of Study Drug 14. Any known or suspected condition of the potential participant that could jeopardize participant adherence to study requirements or impede the accurate assessments of efficacy 15. Males and females of childbearing potential who are unwilling to use highly effective contraceptive methods throughout the study 16. Pregnant or breastfeeding females 17. Alcohol intolerance or dependence (alcoholism) 18. Epilepsy that may be exacerbated by alcohol intake
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that treatment with VL-2397 is non-inferior to standard treatment (voriconazole (with TDM), isavuconazole, or liposomal amphotericin) in the comparison of ACM at 4 weeks in immunocompromised adults with possible, probable, or proven IA. ; Secondary Objective: To demonstrate that treatment with VL-2397 for 28 days followed by voriconazole, isavuconazole, or liposomal amphotericin B is non-inferior to Standard Treatment in the comparison of ACM at 6 weeks in immunocompromised adults with possible, probable, or proven IA. To provide supportive information for the primary and key secondary endpoints and to provide further information on potential uses and benefits of VL-2397. To analyze the full (intensive) PK profile of VL-2397 in at least 10 participants; to analyze sparse PK from all other participants. ;Primary end point(s): ACM at 4 weeks in the ITT population;Timepoint(s) of evaluation of this end point: at 4 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ACM at 6 weeks in the ITT Population. To provide supportive information for the primary and key secondary endpoints and to provide further information on potential uses and benefits of VL-2397 ;Timepoint(s) of evaluation of this end point: at 6 weeks | — |
Countries
Belgium, Canada, France, Germany, Korea, Republic of, United States
Contacts
Public ContactMammen P. Mammen, Jr.
Vical Incorporated
Outcome results
None listed