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    Summary
    EudraCT Number:2017-001275-23
    Sponsor's Protocol Code Number:OTL-101-5(17IC04)
    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:2017-07-03
    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 number2017-001275-23
    A.3Full title of the trial
    Efficacy and safety of a cryopreserved formulation of autologous CD34+ haematopoietic stem cells transduced ex vivo with EFS lentiviral vector encoding for human ADA gene in subjects with Severe Combined Immunodeficiency (SCID) due to Adenosine Deaminase Deficiency
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial to study the effects of genetically modified patients' CD34+ cells
    A.4.1Sponsor's protocol code numberOTL-101-5(17IC04)
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGreat Ormond Street Hospital for Children NHS Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportOrchard Therapeutics
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUCL Institute of Child Health
    B.5.2Functional name of contact pointCecile Duret
    B.5.3 Address:
    B.5.3.1Street Address30 Guilford Street
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeWC1N 1E
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44(0)2079052292
    B.5.5Fax number+44(0)2079052810
    B.5.6E-mailc.duret@ucl.ac.uk
    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/3/13/1134
    D.3 Description of the IMP
    D.3.1Product namecryopreserved EFS-ADA LV transduced patient CD34+ cells
    D.3.2Product code OTL-101
    D.3.4Pharmaceutical form Solution for infusion
    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 INNThere is no recommended INN
    D.3.9.3Other descriptive nameAutologous CD34+ HSCs transduced ex vivo with EFS lentiviral vector encoding for the human ADA gene
    D.3.9.4EV Substance CodeSUB176697
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number2000000 to 20000000
    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 No
    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 No
    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
    Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. If not treated in a way that restores immune function, children with SCID usually live only a year or two.
    E.1.1.1Medical condition in easily understood language
    Adenosine Deaminase (ADA) is an enzyme, needed by the body to develop lymphocytes of the immune system. Children who are born with mutations in ADA gene have severe combined immunodeficiency (SCID).
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10066372
    E.1.2Term ADA deficiency
    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
    - Efficacy: Evaluate the overall survival and event free survival 12 months post OTL-101 administration.
    - Safety: The safety and tolerability of OTL-101.
    E.2.2Secondary objectives of the trial
    - Evaluate the overall survival and event free survival 24 months post GTMP administration.
    - Immunoglobulin Replacement therapies prior to and after gene therapy.
    - Safety and tolerability.
    - Performance outcomes and quality of life will be measured by the Karnofsky/Lansky scale and questions relevant to general well-being, school attendance and ability to practice sports, respectively.
    - Evaluation of the frequency of severe infections or opportunistic infectious episodes; defines as infections or severe infections requiring hospitalisation or prolonged hospitalisation and/or documented infections by opportunistic pathogens (i.e. interstitial pneumonia, intractable diarrhoea).
    - Response to tetanus vaccination.
    - Immune reconstitution: T and B cell reconstitution.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provision of written informed consent prior to any study related procedures. In this study consent must be provided by the parents/legal guardians and, where applicable according to local laws, a signed assent from the child,
    2. Subjects ≥30 days and <18 years of age,
    3. With a diagnosis of ADA-SCID based on evidence of ADA deficiency or evidence of ADA-SCID,
    4. Ineligible for or with no available matched family donor for allogeneic BM transplantation, defined as the absence of a medically eligible HLA-identical sibling or family donor, with normal immune function, who could serve as an allogeneic bone marrow donor.
    5. Females of child-bearing age will be required to provide a negative pregnancy test 30 days prior to Visit 2,
    6. Subjects and their parents/legal guardians must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow up evaluation as specified in the protocol.
    E.4Principal exclusion criteria
    1. Ineligible for autologous haematopoietic stem cell (HSC) procedure.
    2. Other conditions which in the opinion of the Principal Investigator and/or Co Investigators, contraindicate the harvest of bone marrow, the administration of busulfan and the infusion of transduced cells, or which indicate an inability of the subject or subject’s parent/legal guardian to comply with the protocol
    3. Haematologic abnormality,
    4. Pulmonary abnormality,
    5. Cardiac abnormality,
    6. Neurologic abnormality,
    7. Renal abnormality,
    8. Hepatic/gastrointestinal abnormality,
    9. Oncologic disease,
    10. Known sensitivity to Busulfan,
    11. Confirmation of an infectious disease by deoxyribonucleic acid (DNA) PCR positive at time of assessment for the following: HIV-1, Hepatitis B, Parvovirus B19,
    12. The subject is pregnant or has a major congenital anomaly,
    13. Is likely to require treatment during the study with drugs that are not permitted by the study protocol,
    14. The subject has previously received another form of gene therapy.


    E.5 End points
    E.5.1Primary end point(s)
    Evaluate the overall survival and event free survival 12 months post OTL-101 administration.
    Overall survival is defined as the proportion of subjects alive. Event free survival is defined as the proportion of subjects alive with no “event”; an “event” being the resumption of PEG-ADA ERT or the need for a rescue allogenic HSCT, or death.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months post OTL-101 administration
    E.5.2Secondary end point(s)
    - Evaluate the overall survival and event free survival 24 months post OTL-101 administration
    - Immunoglobulin Replacement therapies prior to and after gene therapy.
    - Safety and tolerability.
    - Performance outcomes and quality of life will be measured by the Karnofsky/Lansky scale and questions relevant to general well-being, school attendance and ability to practice sports.
    - Evaluation of the frequency of severe infections or opportunistic infectious episodes, defines as infections or severe infections requiring hospitalisation or prolonging hospitalisation and/or documented infections by opportunistic pathogens (i.e. interstitial pneumonia, intractable diarrhoea).
    - Response to tetanus vaccination.
    - Immune reconstitution: T and B cell reconstitution.
    E.5.2.1Timepoint(s) of evaluation of this end point
    24 months post OTL-101 administration
    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) No
    E.7.1.1First administration to humans No
    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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    The study will have ended after the last subject has completed the last study visit at 24 months post OTL-101 infusion.
    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 months4
    E.8.9.1In the Member State concerned days
    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: 10
    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: 5
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 4
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 1
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    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 finalisation of this study subjects will be invited and encouraged to participate in a registry for long term data collections according to recommendation by the guidelines.
    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 Decision2017-09-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-09-21
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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