Leukocyte Adhesion Deficiency-I (LAD-I) MedDRA version: 20.0 Level: LLT Classification code 10018137 Term: Genetic anomalies of leukocytes System Organ Class: 100000004850
Conditions
Interventions
Product Name: LADICell
Product Code: RP-L201
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: CD34+CELLS
Other descriptive name: CD34+CELLS
Concentration unit: Other
Concentration ty
Sponsors
Rocket Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A confirmed diagnosis of severe LAD-I as demonstrated by flow cytometry indicating CD18 expression on 2% will be considered eligible with =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Availability of a medically-eligible HLA-identical sibling donor transplant. Subjects may not be included in this trial as an alternative to a clinically-indicated and feasible HLA-matched sibling donor HSCT. If an HLA-identical sibling is identified, but mPB or BM HSC collection is not feasible (for example: donor is in utero, is a newborn from whom cord blood was not collected, or is unable to undergo donation procedure because of medical impairments), then inclusion may be permitted per Investigator discretion. 2. Hepatic dysfunction as defined by either: • Bilirubin >1.5× the ULN or • ALT or AST >2.5×ULN 3. Renal dysfunction as defined by either Grade 3 or higher abnormalities in serum sodium, potassium, calcium, magnesium or phosphate as defined by NCI CTCAE v5.0, or the requirement for either peritoneal dialysis or hemodialysis. 4. Pulmonary dysfunction as defined by either: • need for supplemental oxygen during the prior 2 weeks (in absence of acute infection). • Oxygen saturation (by pulse oximetry) <90%. 5. Evidence of active metastatic or locoregionally advanced malignancy (including hematologic malignancy) for which survival is anticipated to be less than 3 years. 6. Serious infections with persistent bloodstream pathogens at time of trial entry. (Subjects with active infections (e.g., unresolved ulcerative lesions, skin or oral infections) are permitted as long as appropriate antibiotic therapy has been (or is being) administered.) 7. Any medical or other contraindication for both leukapheresis and BM harvest procedure, as determined by the treating Investigator. 8. Any medical or other contraindication for the administration of conditioning therapy, as determined by the treating Investigator. 9. Significant medical conditions, including documented HIV infection, poorly controlled diabetes, poorly-controlled hypertension, poorly-controlled cardiac arrhythmia or congestive heart failure; or arterial thromboembolic events (including stroke or myocardial infarction) within the 6 prior months. 10. Any medical or psychiatric condition that in the opinion of the Investigator renders the subject unfit for trial participation or at higher than acceptable risk for participation. Subjects who are evaluated for the trial and determined ineligible may be subsequently evaluated and declared eligible if the criteria by which they were considered ineligible is reversible (e.g., bloodstream infection, transient increase in liver enzymes) and there is documented and plausible evidence of its resolution in the opinion of the principal investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Trial Phase I : • To characterize the safety and toxicity associated with infusion of investigational product:autologous CD34+ cells transduced with the therapeutic LV (Chim-CD18-WPRE LV) Trial Phase II • Survival, as determined by the proportion of subjects alive at age 2 (24 months) and at least 1-year post-investigational product infusion without allogeneic HSCT. • Characterization of the safety and toxicity associated with infusion of the investigational product: autologous CD34+ cells transduced with the therapeutic LV (Chim-CD18- WPRE LV).;Secondary Objective: • Determination of the percentage of subjects in whom infusion of investigational product results in increase in the percentage of neutrophils expressing CD18 to at least 10%after 6 months. • Determination of the percentage of subjects in whom infusion of investigational product results in at least 10% of PB neutrophils carrying the therapeutic Chim-CD18-WPRE LV provirus at 6 months post-infusion. • Determination of the incidence and severity of bacterial or other infections (subsequent to hematopoietic reconstitution). • Evaluation of decreases (partial or to normal levels) of LAD-I-associated neutrophilia. • Evaluation of resolution (partial or complete) of any underlying skin rash or periodontal abnormalities. • Assessment of overall survival (beyond age 24 months and beyond the initial year subsequent to investigational therapy).;Primary end point(s): Alive at age 2 (24 months) and at least 1-year post-investigational product infusion without allogeneic HSCT post-investigational product infusion.;Timepoint(s) of evaluation of this end point: Throughout the duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: • Change in the CD18 expression from pre-infusion to post-infusion (and increased expression of additional beta-2 integrin components CD11a and CD11b) in PB neutrophils, as determined by flow cytometry, including assessment of the percentage of subjects with CD18 expression on at least 10% of neutrophils. • Overall survival and overall health status. • Chim-CD18-WPRE LV VCN in blood and BM cells, as determined via quantitative PCR (qPCR) or digital droplet (dd)PCR at specified time points pre- and post-infusion, including assessment of the percentage of subjects with PB neutrophil VCN of at least 0.1. Safety endpoints • Insertional mutagenesis: Evaluation of gene modified clonal repertoire and lentiviral ISA in blood and, if feasible, BM cells via linear amplification mediated (LAM)-PCR. • RCL (as required and in settings where there is clinical suspicion of unexplained viral illness) in blood. • Immunogenicity: Evidence of antibodies against CD18 (or other ß2-integrin components CD11a or CD11b, or LV components) in blood (serum) (if necessary, in settings where there is clinical suspicion of immunogenic response or evidence of decreasing CD18 expression). • Incidence of respiratory complications (including, but not limited to, pneumonitis) • Incidence of hepatic complications (including, but not limited to, VOD).;Timepoint(s) of evaluation of this end point: Throughout the duration of the study | — |
Countries
Spain, United Kingdom, United States
Contacts
Public ContactChief Medical Officer
Rocket Pharmaceuticals, Inc
Outcome results
None listed