Pyruvate kinase deficiency MedDRA version: 20.0 Level: PT Classification code 10037682 Term: Pyruvate kinase deficiency anaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: MERILEN
Product Code: RP-L301
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: MERILEN
CAS Number: N/A
Sponsors
Rocket Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. PKD diagnosis with a confirmed PKLR mutation. 2. Age =18 years old and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Presence of other known causes of hemolysis (in addition to PKD). Patients with concurrent G6PD deficiency diagnosed during pre-study evaluation may be considered for eligibility if in the opinion of the Investigator, the hemolytic anemia is the result of PKD and the G6PD deficiency is considered an incidental finding. 2. A venous thromboembolic event (VTE; i.e., pulmonary embolism or deep vein thrombosis) or arteriothromboembolic event (ATE; including unstable angina, myocardial infarction, stroke or transient ischemic attack) during the prior 12 months. 3. Any evidence of severe iron overload that, per Investigator discretion, warrants exclusion. 4. Evidence of bridging fibrosis, cirrhosis or active hepatitis on liver biopsy. Liver biopsy is required when liver iron concentration (LIC) is =15 mg/g on T2* magnetic resonance imaging (MRI) of liver. If a liver biopsy has been performed less than 6 months prior to enrollment, it does not need to be repeated. 5. Significant medical conditions including documented HIV infection, active viral hepatitis, poorly-controlled hypertension, pulmonary hypertension, cardiac arrhythmia or congestive heart failure; or ATEs (including stroke or myocardial infarction) within the 6 prior months. 6. Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or another carcinoma in situ. Patients with previously resected solid organ malignancies or definitively treated hematologic malignancies may be eligible if there has been no evidence of active malignancy during the prior 3 years. 7. Uncontrolled seizure disorder. 8. Cardiac T2*2.5× the ULN 10. Renal dysfunction defined as serum creatinine >ULN. Patients with creatinine above ULN may be eligible pending documentation of a glomerular filtration rate (GFR) =60 mL/min/1.73m2 as calculated by Modification of Diet in Renal Disease equation, the revised Schwartz formula (for patients under 18 years old), or 24-hour urine collection. 11. Pulmonary dysfunction as defined by either: • Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection) or • Oxygen saturation (by pulse oximetry) <90%. 12. Any medical or other contraindication for both leukapheresis and BM harvest procedure as determined by the treating Investigator. 13. 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. 14. Poor functional status, evidenced by Karnofsky Index <70 in adults or Lansky <70 in children. 15. Participation in another clinical trial with an investigational drug within 14 days before the informed consent signature. Participation in observational studies is allowed. 16. Pregnant women or women with a positive serum pregnancy test at screening or breast feeding or planning to become pregnant within the next 24 months. Women not willing to use highly effective contraceptive methods during the complet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of trial Phase 1 is to characterize the safety and toxicity associated with infusion of the investigational product: autologous CD34+ cells transduced with the therapeutic LV, PGK-coRPK-WPRE.;Secondary Objective: Not applicable;Timepoint(s) of evaluation of this end point: Throughout the duration of the study; Primary end point(s): Safety assessments specifically relevant to gene therapy are as follows: 1. Insertional mutagenesis: Evaluation of gene-modified clonal repertoire and lentiviral ISA in blood and, if feasible, BM cells via modified gene sequencing (MGS)-PCR. 2. RCL (as required and in settings where there is clinical suspicion of unexplained viral illness) in blood. 3. Immunogenicity: Evidence of antibodies against coRPK (or other LV components) in blood (serum) (if necessary in settings where there is clinical suspicion of immunogenic response or evidence of decreasing coRPK expression). Other assessments include: 1. Achievement of stem cell engraftment =45 days after infusion. Engraftment is defined as first day with neutrophil count >500/µL and platelets >20,000/µL on 3 consecutive blood counts. 2. Time to stem cell engraftment. 3. Incidence of respiratory complications (including, but not limited to, pneumonitis). 4. Incidence of hepatic complications (including, but not limited to, veno-occlusive disease (VOD)). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are as follows: 1. PB and BM genetic correction, as demonstrated by VCN subsequent to investigational product infusion and evidence of multi-lineage gene correction in PB and BM cells. 2. Transfusion independence at 12 months defined as need for =1 transfusion in the previous 6 months. 3. Achievement of 50% reduction in transfusion requirements at 12 months (assessed in the previous 6 months for the 12-month assessment) relative to the 1-year period prior to enrollment (not including transfusions administered to support/facilitate HSC collection). 4. Clinically significant reduction of anemia defined as either: - An increase in pre-transfusion Hb levels of 1.5 g/dL (determined by 2 assessments separated at least three months over the first and second year of follow up) relative to the average of a patient’s Hb levels before therapeutic blood transfusion administrations over the year prior to enrollment OR - An increase of at least two-fold in the time to pre-transfusion Hb nadir relative to the average transfusion interval over the year prior to enrollment, where pretransfusion Hb nadir is defined as the average Hb value (during the year prior to enrollment) prior to RBC transfusions. 5. Reduction of hemolysis. The following endpoints will be assessed in accordance: - Clinically significant reduction of reticulocytosis, defined as number of patients with a reduction of 50% from the average of a patient’s absolute reticulocyte counts from therapeutic blood transfusion administrations over the year prior to enrolment at 12 months subsequent to investigational therapy. Exploratory endpoints will include: 1. Assessment of normalization of additional circulating parameters characteristic of anemia and/or hemolysis, including reductions | — |
Countries
Spain, United States
Contacts
Public ContactChief Medical Officer
Rocket Pharmaceuticals, Inc.
Outcome results
None listed