X-linked chronic granulomatous disease MedDRA version: 18.0 Level: PT Classification code 10008906 Term: Chronic granulomatous disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Ibuprofen
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IBUPROFEN
CAS Number: 15687-27-1
Current Sponsor code: NA
Other descriptive name: NA
Concentration unit: mg millig
Sponsors
Ospedale San Raffaele
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: •Genetic diagnosis of X-CGD •18-45 years of age •Karnofsky Index > 80 % •Adequate cardiac, renal, hepatic and pulmonary function. •Negative thrombophilic screen and negative history for previous thrombotic events •Written informed consent. 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 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Previous Bone Marrow Transplantation or previous Gene Therapy. •Use of other investigational agents within 4 weeks prior to study en-rolment (within 6 weeks if use of long-acting agents). •Ongoing IFN-? treatment (within 4 weeks). •Symptomatic inflammatory bowel disease. •Symptomatic viral, bacterial, or fungal infection within 6 weeks of eli-gibility evaluation or active infection (including fever of unknown origin) •Neoplasia (except local skin cancer) or history of “familial” cancer. •Myelodysplasia or other serious hematological disorder •History of uncontrolled seizures and deep venous thrombosis •Other systemic disease judged as incompatible with the procedure •Positivity for HIV and/or HCV RNA and/or HbsAg and/or HBV DNA •Active alcohol or substance abuse within 6 months of the study. •Contraindications to IBU, G-CSF, Plerixafor or Pantoprazole administration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To explore the safety of IBU, G-CSF and Plerixafor when administered as a stem cell mobilization regimen in patients affected by X-CGD. 2.To explore the effect of IBU, G-CSF and Plerixafor in mobilizing CD34+ cells thus allowing the collection of a number of HSPC deemed sufficient for ex vivo gene therapy in patients affected by X-CGD. ;Secondary Objective: 1.To explore the effect of Ibuprofen in mobilizing CD34+ cells in the PB. 2.To explore the in vitro efficacy of a lentiviral vector encoding for a corrective cDNA of the human gp91phox gene in transducing CD34+ cells obtained by the XCGD-MOBI protocol and correcting the func-tional defects in the differentiated myeloid progeny. 3.To functionally characterize the properties of IBU, G-CSF and Plerixafor mobilized CD34+ cells from X-CGD patients ;Primary end point(s): 1) Safety Incidence and severity of adverse events following IBU, G-CSF and Plerixafor administration (any grade) occurring between day 0 and 30 days after the last LP. 2) Efficacy - Harvest of >= 8X10^6 CD34+/Kg in one or more collections;Timepoint(s) of evaluation of this end point: 1) From Day 0 to 30 days after the last LP 2) from the first to the last LP | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Increase in PB CD34+ cell count after administration of Ibuprofen. 2.Efficient transduction of mobilized HSPC and oxidase activity restoration in their myeloid progeny following gene transfer with a lentiviral vector encoding for human gp91phox. 3.Maintenance of repopulating activity of transduced HSPC in immunodeficient mice ;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Italy
Contacts
Public ContactTIGET Clinical Trial Office (TCTO)
Ospedale San Raffaele
Outcome results
None listed