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Study of EBT-101 in Aviremic HIV-1 Infected Adults on Stable ART

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.
 
ClinicalTrials.gov Identifier: NCT05144386
Recruitment Status : Recruiting
First Posted : December 3, 2021
Last Update Posted : October 19, 2022
Sponsor:
Information provided by (Responsible Party):
Excision BioTherapeutics

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
HIV-1-infection Biological: EBT-101 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a, Sequential Cohort, Single Ascending Dose Study of the Safety, Tolerability, Biodistribution, and Pharmacodynamics of EBT 101 in Aviremic HIV-1 Infected Adults on Stable Antiretroviral Therapy
Actual Study Start Date : January 24, 2022
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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




Primary Outcome Measures :
  1. Safety and Tolerability of EBT-101 [ Time Frame: 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



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:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Cohort A will enroll male adults (sex at birth)
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (abbreviated):

  • Willing to enroll and sign the written informed consent for EBT-101-001 (current study) and EBT-101-002, the LTFU study.
  • Age between 18 and 65 years (both inclusive).
  • Body weight ≥45 and ≤90 kg.
  • Cohort A will only enroll male subjects (sex at birth).
  • Chronic HIV-1 infection
  • On stable regimen defined as continuous ART treatment for >2 years prior to screening; no changes in regimen or missed doses for ≤90 days prior to the planned dosing date.
  • 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 42 days prior to the planned dosing date
  • Peripheral blood CD4 T cell count >350 cells/mm3 within the last 2 years prior to screening
  • Normal laboratory values in hematology, hepatic, renal and other systems for lab safety screening.
  • Willing and able to comply, as assessed by the Investigator, with all study-related procedures.
  • Have previously been vaccinated for N. meningitidis with documented history and/or received a N. meningitidis vaccination prior to dosing.
  • Willing to stop ART if eligible for analytical treatment interruption.
  • Willing to comply with the measures to prevent HIV transmission and reinfection required by the protocol.
  • Must have received a COVID-19 vaccination series and boosters as specified by current federal (CDC) recommendations, with the last dose ≥30 days prior to dosing.

Exclusion Criteria (abbreviated):

  • 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.
  • History of >1 change in ART due to virologic failure during preceding 2 years.
  • Received in the preceding 12 months or HCP plans to prescribe long-acting injectable ART.
  • Pregnant or breastfeeding or planning to become pregnant (self or partner) or to breastfeed at any time through 48 weeks post dose.
  • History of HIV dementia.
  • History of progressive multifocal leukoencephalopathy.
  • History of significant cardiac disease in last 2 years.
  • History of HIV-related kidney disease with abnormal renal function.
  • History of one or more HIV-related opportunistic infections or within the past 2 years.
  • Evidence of acute or chronic hepatitis B and/or hepatitis C.
  • Known history or diagnosis of liver cirrhosis.
  • Diagnosis of nonalcoholic fatty liver or advanced nonalcoholic steatohepatitis.
  • Known history of positive tuberculin skin test.
  • Receipt of any investigational HIV vaccine (prophylactic and/or therapeutic) within the year prior to screening.
  • Receipt of any gene therapy product approved or experimental, at any time.
  • Anti-AAV9 serum neutralizing antibodies (Nabs) >1:20 titer.
  • Known positive SARS-CoV-2 test within 48 hours prior to planned dosing date.

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 ClinicalTrials.gov identifier (NCT number): NCT05144386


Contacts
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Contact: Study Director at ExcisionBio 833-214-2241 clinicalscience@excisionbio.com
Contact: Study Lead at ExcisionBio clinicalscience@excisionbio.com

Locations
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United States, California
University of California San Francisco Recruiting
San Francisco, California, United States, 94110
Contact: Shreya Swaminathan    628-206-5801    Shreya.Swaminathan@ucsf.edu   
Contact: Victor Arechiga    628-206-5432    Victor.Arechiga@ucsf.edu   
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Michael Klebert    314-454-0058    mklebert@wustl.edu   
United States, New Jersey
Cooper Health Recruiting
Camden, New Jersey, United States, 08103
Contact: Yolanda Smith    856-968-8651    smith-yolanda@cooperhealth.edu   
Sponsors and Collaborators
Excision BioTherapeutics
Investigators
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Study Director: Study Director Excision BioTherapeutics
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Responsible Party: Excision BioTherapeutics
ClinicalTrials.gov Identifier: NCT05144386    
Other Study ID Numbers: EBT-101-001
First Posted: December 3, 2021    Key Record Dates
Last Update Posted: October 19, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Excision BioTherapeutics:
CRISPR
Gene Therapy
AAV9
HIV