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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 4 September 2023
Main ID:  NCT04145037
Date of registration: 27/08/2019
Prospective Registration: No
Primary sponsor: AVROBIO
Public title: Lentiviral Vector Gene Therapy - The Guard1 Trial of AVR-RD-02 for Subjects With Type 1 Gaucher Disease
Scientific title: The Guard1 Trial, an 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
Date of first enrolment: May 30, 2019
Target sample size: 7
Recruitment status: Terminated
URL:  https://clinicaltrials.gov/ct2/show/NCT04145037
Study type:  Interventional
Study design:  Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 1/Phase 2
Countries of recruitment
Australia Canada United States
Contacts
Name:     Milena Veselinovic, MD
Address: 
Telephone:
Email:
Affiliation:  AVROBIO
Key inclusion & exclusion criteria

INCLUSION CRITERIA for all Enrolled (Switch-stable and Treatment-naïve) Subjects:

1. Subject is =18 and =50 years old and post pubertal

2. Subject has a confirmed diagnosis of Type 1 Gaucher disease based on deficient GCase
enzyme at Screening.

a. For switch-stable subjects, documentation of GCase enzyme activity prior to having
been started on ERT or if GCase levels prior to ERT are not available, deficient
trough GCase enzyme activity in peripheral blood at Screening.

3. Female subjects of reproductive potential will be counseled regarding the risks,
benefits, limitations, and alternatives associated with female fertility preservation.
Oocyte harvesting and cryopreservation will be offered

4. Male subjects must be willing to refrain from donating sperm at any time after
receiving conditioning therapy. For subjects planning on (or for whom there is a
possibility of) fathering children in the future, sperm cryopreservation before
administration of the conditioning regimen will be recommended.

5. All subjects who have not undergone successful surgical sterilization (ie, vasectomy,
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) must agree to
remain sexually abstinent or use two effective methods of contraception while sexually
active from the day of conditioning administration until 52 weeks post-gene therapy
infusion. Two methods of contraception are required even with documented medical
assessment of surgical success of sterilization.

1. For male subjects and for male spouses/partners of female subjects, condoms are
an acceptable method of barrier contraception

2. For female subjects and for female spouses/partners of male subjects, acceptable
methods of barrier contraception include diaphragm, cervical cap, or
contraceptive sponge

6. Male and female subjects must agree to refrain from donating sperm and eggs,
respectively, after undergoing conditioning.

7. Subject must be willing to refrain from donating blood, organs, tissues, or cells for
gene therapy infusion any time after AVR-RD-02 treatment.

8. Subject must be willing and able to provide written informed consent for the study in
accordance with applicable regulations and guidelines and to comply with all study
visits and procedures, including the use of any data collection device(s) that may be
used to directly record subject data.

9. Subject must be willing to receive blood or blood products transfusion to manage
adverse events (AEs).

Additional Inclusion Criteria for Switch-stable Subjects (in addition to criteria 1-9
above):

10. Subject has undergone a stable dose (within 75% to125% of the prescribed dose) of ERT
= 15 U/kg and = 60 U/kg every other week (or equivalent) for = 24 consecutive months
with no significant interruptions, in dosing over the last 6 months, in the opinion of
the Investigator, prior to Screening

11. Subject has normal or near-normal hematologic values at Screening defined as one or
more of the following:

1. Hemoglobin concentration =10 g/dL

2. Platelet count =80 x 10^9/L

12. Subject has stable Gaucher disease during the 6 months immediately preceding Screening
defined by:

1. Stable hemoglobin concentration (i.e., within a range of ±2 g/dL of the Screening
value) based on documented historical clinical laboratory results and

2. Stable platelet count (within ±20% of the Screening value) based on documented
historical clinical laboratory results

13. Subject has not received SRT for Gaucher disease within 12 months of Screening.

Additional Inclusion Criteria for Treatment-naïve Subjects (in addition to inclusion
criteria 1 through 9, above, treatment-naïve subjects must meet the following
inclusion criteria for participation in this study):

14. Subject has neither received ERT nor SRT for Gaucher disease nor has received neither
ERT nor SRT for Gaucher disease within 12 months of Screening.

15. Subject has a hemoglobin level =2 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 <120 x 10^9/L

2. Enlarged liver by palpation, confirmed on abdominal MRI

3. Moderate splenomegaly by palpation, confirmed on abdominal MRI

16. For any subject who is treatment-naïve, ERT peri-procedurally (from the Screening
Period throughout 2 weeks prior to Gene Therapy Infusion) will be considered in
consultation with the PI and Sponsor Medical Monitor.

EXCLUSION CRITERIA:

1. Subject has Type 2 or 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.

2. Subject has any one of the following:

1. Hemoglobin value <9.0 g/dL, or

2. Platelet count <70 x 10^9/L, or

3. Spleen volume >10 x normal, or

4. Pulmonary hypertension

3. Subject has experienced a prior anaphylactic or anaphylactoid reaction (of any
severity) to ERT.

4. Treatment-naïve subject has history of clinically significant (CS) anti-GCase
antibodies.

5. Subject has a contraindication to ERT, in the opinion of the Investigator.

6. Subject has a contraindication to HSC transplantation (HSCT), in the opinion of the
Investigator.

7. Subject presents with iron, folic acid, and/or vitamin B12 deficiency sustained anemia
during Screening.

8. Subject has idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic
purpura (TTP), thrombocytopenia, anemia, hepatomegaly, splenomegaly, and/or
osteoporosis, unrelated to Gaucher disease, in the opinion of the Investigator.

9. Subject has a clinical co-morbidity such as neurologic, cardiovascular, pulmonary,
hepatic, gastrointestinal, renal, hematologic, endocrine, metabolic, genetic,
immunologic, neoplastic, or psychiatric disease, other medical condition(s), or
intercurrent illnesses that may confound the study results or, in the opinion of the
Investigator, may preclude participation in the study.

10. Subject is a pregnant and/or lactating female.

11. Subject is unable to understand the nature, scope, and possible consequences of the
study.

12. Subject has diabetes mellitus (Type 1 or Type 2).




Age minimum: 18 Years
Age maximum: 50 Years
Gender: All
Health Condition(s) or Problem(s) studied
Gaucher Disease
Intervention(s)
Drug: AVR-RD-02
Primary Outcome(s)
Change from Baseline in plasma lyso-Gb1 levels by liquid chromatography tandem mass spectrometry (LC/MS/MS) [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Change from Baseline in platelet count [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Change from Baseline in hemoglobin concentration [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Change from Baseline in spleen volume assessed by abdominal MRI [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Incidence of clinically significant Adverse Events and Serious Adverse Events of AVR-RD-02 [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Number of participants with clinically relevant abnormalities, as assessed by electrocardiograms (ECGs) [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Number of participants with clinically relevant abnormalities, as assessed by clinical laboratory tests [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Number of participants with clinically relevant abnormalities, as assessed by vital signs [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Average Vector Copy Number (VCN) in bone marrow as assessed by quantitative polymerase chain reaction (qPCR) and/or droplet digital polymerase chain reaction (ddPCR) [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Average Vector Copy Number (VCN) in peripheral blood as assessed by quantitative polymerase chain reaction (qPCR) and/or droplet digital polymerase chain reaction (ddPCR) [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Change from Baseline in liver volume assessed by abdominal MRI [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Secondary Outcome(s)
Change from average of Screening and Baseline over time in glucocerebrosidase (GCase) enzyme activity [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Change from Baseline in Bone Mineral Density (BMD) assessed by Bone Density Scan (DXA) [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Change from Baseline in anti-GCase total antibodies and subsequent titers by an electrochemiluminescence method [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Change from Baseline in plasma Chitotriosidase activity levels measured by fluorometric enzyme assay [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Change from Baseline in Bone Marrow Burden (BMB) Score as assessed by bone Magnetic Resonance Imaging (MRI) [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Incidence of Enzyme Replacement Therapy (ERT) utilized following treatment with AVR-RD-02 [Time Frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up]
Secondary ID(s)
AVRO-RD-02-201
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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