Study of EBT-101 in Aviremic HIV-1 Infected Adults on Stable ART
Study Details
Study Description
Brief Summary
This is a First in Human (FIH) study of EBT-101 administered IV to aviremic HIV-1 infected adults on stable antiretroviral therapy (ART).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a FIH, open-label, sequential cohort, single ascending dose (SAD) study of EBT-101 administered IV to aviremic HIV-1 infected adults on stable ART.
Participants will be asked to attend several visits for screening to determine eligibility. On Day 1, eligible participants will receive a single IV dose of EBT-101. All participants will be assessed for eligibility for an analytical treatment interruption (ATI) of their background ART at Week 12. All participants will be followed through Week 48 (end of study). Participants are required to attend multiple study visits at the clinical site including daily visits for the first 14 days, followed by weekly visits from Week 12 to Week 48. Non-ATI participants are followed less frequently after Week 12.
Eligible participants who are enrolled in the FIH study (EBT-101-001) will also be enrolled in a separate Long Term Follow Up (LTFU) study (EBT-101-002) for safety monitoring. The duration of the LTFU study will be up to 15 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EBT-101 Dose-Level 1 Cohort A: Participants will be administered dose-level 1 of EBT-101 |
Biological: EBT-101
EBT-101 is a HIV-1-specific clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by adenovirus-associated virus vector serotype 9 (AAV9) for intravenous (IV) administration
|
| Experimental: EBT-101 Dose-Level 2 Cohort B: Participants will be administered dose-level 2 of EBT-101 |
Biological: EBT-101
EBT-101 is a HIV-1-specific clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by adenovirus-associated virus vector serotype 9 (AAV9) for intravenous (IV) administration
|
| Experimental: EBT-101 Dose-Level 3 Cohort C: Participants will be administered dose-level 3 of EBT-101 |
Biological: EBT-101
EBT-101 is a HIV-1-specific clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by adenovirus-associated virus vector serotype 9 (AAV9) for intravenous (IV) administration
|
Outcome Measures
Primary Outcome Measures
- Safety and Tolerability of EBT-101 [48 weeks]
Safety and tolerability of EBT-101 will be assessed based on the incidence and severity of adverse events (AEs) according to Division of AIDS (DAIDS) 2017 over 48 weeks
Eligibility Criteria
Criteria
Inclusion Criteria (abbreviated):
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Willing to enroll and sign the written informed consent for EBT-101-001 (current study) and EBT-101-002, the LTFU study.
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Age between 18 and 60 years (both inclusive).
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Body weight ≥45 and ≤90 kg.
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Cohort A will only enroll male subjects (sex at birth).
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Documented chronic HIV-1 infection with the following management status criteria: on a stable regimen defined as continuous ART treatment for >2 years prior to screening; no interruptions within the last 12 months greater than 14 consecutive days; no changes in regimen or doses for >90 days prior to the planned dosing date; regimen will be maintained throughout the study duration.
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Plasma HIV-1 RNA levels below the limit of quantification: on all available results in past 12 months (isolated single values ≥20 but <200 copies/mL will be allowed if they were preceded and followed by undetectable viral load results); within 60 days prior to the planned dosing date; peripheral blood CD4 T cell count >500 cells/mm3 within 60 days prior to the planned dosing date.
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Normal laboratory values in hematology, hepatic, renal and other systems for lab safety screening.
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Willing and able to comply, as assessed by the Investigator, with all study-related procedures.
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Have previously been vaccinated for N. meningitidis with documented history and/or received a N. meningitidis vaccination prior to dosing.
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Willing to stop ART if eligible for analytical treatment interruption.
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Willing to comply with the measures to prevent HIV transmission and reinfection required by the protocol.
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Must have received a COVID-19 vaccine, with the last dose ≥30 days prior to dosing.
Exclusion Criteria (abbreviated):
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Documented prior HIV-1 drug resistance to ≥2 or more classes of ART defined as single key mutations or an accumulation of minor mutations that result in resistance to entire respective drug classes within the past 5 years.
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History of >1 change in ART due to virologic failure during preceding 2 years.
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Receiving or have plans to start long-acting injectable ART.
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Pregnant or breastfeeding or planning to become pregnant (self or partner) or to breastfeed at any time through 48 weeks post dose.
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History of HIV dementia.
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History of progressive multifocal leukoencephalopathy.
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History of known cardiovascular event in the past year or history of HIV-related cardiac disease.
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History of HIV-related kidney disease with abnormal renal function.
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History of one or more HIV-related opportunistic infections or within the past 2 years.
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Evidence of acute or chronic hepatitis B (positive serum hepatitis B surface antigen [HBsAg], positive serum hepatitis B core antibody [anti-HBcAb]) and/or hepatitis C (detectable plasma HCV-RNA).
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Known history or diagnosis of liver cirrhosis, nonalcoholic fatty liver or advanced nonalcoholic steatohepatitis.
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Known history of positive tuberculin skin test.
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Receipt of any investigational HIV vaccine (prophylactic and/or therapeutic) within the year prior to screening.
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Receipt of any gene therapy product approved or experimental, at any time.
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Anti-AAV9 serum neutralizing antibodies (Nabs) >1:20 titer.
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Known positive SARS-CoV-2 test within 30 days prior to screening and/or persistent (long) COVID-19-related symptoms during screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Trial Site | San Francisco | California | United States | 94110 |
| 2 | Washington University | Saint Louis | Missouri | United States | 63110 |
| 3 | Cooper Health | Camden | New Jersey | United States | 08103 |
Sponsors and Collaborators
- Excision BioTherapeutics
Investigators
- Study Director: Study Director, Excision BioTherapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EBT-101-001