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Trial record 1 of 1 for:    AVR-RD-02 | Gaucher Disease, Type 1
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Phase 1/2 Lentiviral Vector Gene Therapy - The GuardOne Trial of AVR-RD-02 for Subjects With Type 1 Gaucher Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04145037
Recruitment Status : Recruiting
First Posted : October 30, 2019
Last Update Posted : February 17, 2020
Information provided by (Responsible Party):

Brief Summary:
This is an adaptive, multinational, open-label study to assess the safety and efficacy of AVR-RD-02 in approximately 8 to 16 subjects (male or female) who are ≥16 and ≤35 years of age and postpubertal at Screening with a confirmed diagnosis of Type 1 Gaucher disease (based on clinical phenotype, genotyping, and deficient GCase enzyme activity in plasma and PBLs).

Condition or disease Intervention/treatment Phase
Gaucher Disease Drug: AVR-RD-02 Phase 1 Phase 2

Detailed Description:

The duration of each subject's participation in this study will be approximately 68 weeks (or 1 year, 16 weeks), comprised of a five study periods (Screening, Baseline, Pre-transplant, Transplant, and Post-transplant Follow-up). During the Screening Period (up to 60 days), written informed consent (and assent, if applicable) will be obtained and the subject will complete other Screening procedures to confirm study eligibility. Once study eligibility is confirmed, subjects will enter the Baseline Period (up to 3 days) during which time assessments will be performed to establish a pre-transplant baseline. Once baseline assessments are complete, the subject will enter the Pre-transplant Period (approximately 6-8 weeks) during which time mobilization, apheresis, AVR-RD-02 drug product preparation and testing for release, and planned conditioning regimen administration will take place. Enzyme replacement therapy must be discontinued at least 2 weeks before the scheduled transplant day. Following completion of the Pre-transplant Period, the subject will enter the Transplant Period (1 day) during which AVR-RD-02 infusion will take place. After AVR-RD-02 infusion, the subject will enter the Post-transplant Follow-up Period (approximately 52 weeks), during which time periodic safety and efficacy assessments will be performed to assess measures of safety, engraftment, and clinical response post-transplant. Post-transplant follow-up will occur at the following time points: Week 1 (Days 1 through 7), Week 2 (Days 10 and 14), Week 4 (Day 28), Week 8 (Day 56), Week 13 (Day 91), Week 26 (Day 182), Week 39 (Day 273), and Week 52 (Day 364). During the post-transplant period, subjects will not receive ERT unless pre-specified clinical criteria, which suggest the need for ERT initiation, are met.

After study completion, subjects enrolled will continue periodic safety and efficacy assessments for approximately 14 years (for a total of 15 years post-transplant follow-up) by way of a follow-up study to AVRO-RD-02-201.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Adaptive, Open-Label, Multinational Phase 1/2 Study Of The Safety and Efficacy of Ex Vivo, Lentiviral Vector-Mediated Gene Therapy AVR-RD-02 for Subjects With Type 1 Gaucher Disease
Actual Study Start Date : May 30, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : September 2022

Arm Intervention/treatment
Experimental: Switch Stable
study arm will include subjects who have been receiving ERT for a minimum of 24 months immediately preceding Screening, have demonstrated clinical stability during the 6 months immediately preceding Screening, and have not been treated with substrate reduction therapy (SRT) during the 24 months immediately preceding Screening (ie, switch-stable subjects). Switch-stable subjects must discontinue ERT prior to transplantation.
Drug: AVR-RD-02
AVR-RD-02 Drug product, ( autologous CD34+ enriched hematopoietic stem cells ( HSCs) that have been genetically modified

Experimental: treatment-naïve
will include subjects who have either never received ERT or SRT, or have not received ERT or SRT within 12 months of screening
Drug: AVR-RD-02
AVR-RD-02 Drug product, ( autologous CD34+ enriched hematopoietic stem cells ( HSCs) that have been genetically modified

Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events of AVR-RD-01 drug product [ Time Frame: baseline to week 52 post gene therapy ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0".

  2. Evaluate GCase enzyme activity following treatment with AVR-RD-02 investigational product. [ Time Frame: baseline to week 52 post gene therapy ]
    Evaluate GCase enzyme activity in plasma and peripheral blood leukocytes in addition to the need for enzyme replacement therapy (ERT) following treatment with AVR-RD-02 investigational product.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   16 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Common Inclusion Criteria for all Enrolled (Switch-stable and Treatment-naïve) Subjects:

  1. Subject is ≥16 and ≤35 years old and postpubertal
  2. Subject has a confirmed diagnosis of Type 1 Gaucher disease based on genotyping, deficient GCase enzyme activity (defined as ≤15%) in PBLs, and clinical phenotype.

    a. For switch-stable subjects documentation of GCase enzyme activity (≤15%) prior to having been started on ERT is required. If GCase levels prior to ERT are not available, trough GCase enzyme activity (≤15%) is required.

    Additional Inclusion Criteria for Switch-stable Subjects:

  3. Subject has undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; any combination of infusions resulting in a total monthly ERT dose of >30 U/kg and <120 U/kg) for ≥24 consecutive months for Gaucher disease at the time of Screening.
  4. Subject has normal or near-normal hematologic values at Screening.
  5. Subject has stable Gaucher disease during the 6 months immediately preceding Screening.
  6. Subject has not received SRT for Gaucher disease during the 24 months immediately preceding Screening.

    Additional Inclusion Criteria for Treatment-naïve Subjects:

  7. Subject has never received either ERT or SRT for Gaucher disease or has not received either ERT or SRT for Gaucher disease within 12 months of Screening.
  8. Subject has a hemoglobin level ≤1 g/dL below the lower limit of normal (LLN) for age and sex at Screening and at least one of the following at Screening:

    1. Platelet count <120X10/9L
    2. Enlarged liver by palpation, confirmed on abdominal MRI
    3. Moderate splenomegaly on abdominal MRI.

    Exclusion Criteria:

    • Exclusion Criteria:
  9. Subject has Type 2 or 3 Gaucher disease, is suspected of having Type 3 Gaucher disease, has severe neurological signs and symptoms, defined as complete ocular paralysis, overt myoclonus or history of seizures, characteristic of neuronopathic Gaucher disease, or has a tremor, peripheral neuropathy or symptoms of Parkinson's disease.
  10. Subject has any one of the following:

    1. Hemoglobin value <9.0 g/dL, or
    2. Platelet count <70X109/L, or
    3. Spleen volume >5 X normal, or
    4. Pulmonary hypertension
  11. Subject has had or is scheduled to undergo a partial or total splenectomy.
  12. Subject has experienced a prior anaphylactic or anaphylactoid reaction (of any severity) to ERT.
  13. Treatment-naïve subject is antibody-positive to GCase.
  14. Subject has a contraindication to ERT.
  15. Subject has idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), thrombocytopenia, anemia, hepatomegaly, splenomegaly, and/or osteoporosis, unrelated to Gaucher disease.
  16. Subject has active, progressive bone necrosis.
  17. Subject has an active chronic infection during the Screening, Baseline, or Pre-transplant Period of the study.
  18. Subject has a prior history of (or current) cancer or precancerous lesion or has a known genetic predisposition to cancer. The one exception is a prior history of resected squamous cell carcinoma.
  19. Subject has previously received treatment with AVR-RD-02 or any other gene therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04145037

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Contact: lisamarie fahy 6179148417

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Australia, Parkville, VIC
Royal Melbourne Hospital Recruiting
Melbourne, Parkville, VIC, Australia, 3050
Contact: joyce wang    0436853838   
Principal Investigator: Kylie Mason, MD         
Canada, Calgary Alberta
University of Calgary Recruiting
Calgary, Calgary Alberta, Canada, T2N 1N4
Contact: Shelly Jelinska    4039557874   
Principal Investigator: Aneal Kahn, MD         
Sponsors and Collaborators
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Study Director: Birgitte Volck, MD AvroBio
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Responsible Party: AvroBio Identifier: NCT04145037    
Other Study ID Numbers: AVRO-RD-02-201
First Posted: October 30, 2019    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Gaucher Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors