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    Summary
    EudraCT Number:2020-000517-33
    Sponsor's Protocol Code Number:RP-L201-0318
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2020-02-21
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2020-000517-33
    A.3Full title of the trial
    Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I):A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced with a Lentiviral Vector Encoding the ITGB2 Gene
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I):A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced with a Lentiviral Vector Encoding the ITGB2 Gene
    A.4.1Sponsor's protocol code numberRP-L201-0318
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorRocket Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportRocket Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRocket Pharmaceuticals, Inc
    B.5.2Functional name of contact pointChief Medical Officer
    B.5.3 Address:
    B.5.3.1Street Address350 5th Avenue, Suite 7530
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 10118
    B.5.3.4CountryUnited States
    B.5.4Telephone number01646440-9100
    B.5.6E-mailjs@rocketpharma.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/16/1753
    D.3 Description of the IMP
    D.3.1Product nameLADICell
    D.3.2Product code RP-L201
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCD34+CELLS
    D.3.9.3Other descriptive nameCD34+CELLS
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number2000000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Yes
    D.3.11.3.5.1CAT classification and reference numberATMP designation H0005238
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeLADICell (RP-L201): Autologous CD34+-enriched cells from patients with LAD-I transduced ex vivo with the therapeutic lentiviral vector encoding for the ITGB2 gene, Chim-CD18-WPRE LV.
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Leukocyte Adhesion Deficiency-I (LAD-I)
    E.1.1.1Medical condition in easily understood language
    Leukocyte Adhesion Deficiency-I (LAD-I)
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10018137
    E.1.2Term Genetic anomalies of leukocytes
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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).
    E.2.2Secondary objectives of the trial
    • 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).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. A confirmed diagnosis of severe LAD-I as demonstrated by flow cytometry indicating CD18 expression on <2% neutrophils (PMNs). Subjects in which CD18+ PMNs are >2% will be considered eligible with <2% CD11a or CD11b expressing PMNs and if there is a documented ITGB2 mutation and clinical history consistent with LAD-I (or known family history).
    2. At least one (1) prior significant bacterial or fungal infection (US NCI CTCAE v5.0, Grade ≥2). This criterion is not required for subjects with documented family history who meet the above inclusion criteria.
    3. Age ≥3 months.
    4. Considered to be an appropriate candidate for autologous transplantation of HSCs.
    5. A competent custodial parent with legal capacity to execute an IRB/EC-approved consent form must be available to participate in the consent process. (Informed assent will be sought from capable subjects, in accordance with the directive of the IRB/EC and with local requirements.)
    6. Ability to comply with trial procedures including investigational therapy and follow up evaluations.
    E.4Principal 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.
    E.5 End points
    E.5.1Primary 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.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Throughout the duration of the study
    E.5.2Secondary 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 β2-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).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the duration of the study
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA2
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 9
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 3
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 6
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children under 12 years old will signed an informed consent form by Legal Representative
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Children under 12 years old will signed an informed consent form by Legal Representative
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 3
    F.4.2.2In the whole clinical trial 9
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After the end of the follow-up period, patients will enter a follow up extension trial for at least 13 additional years (total follow-up 15 years).
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-04-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-07-14
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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