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

NCT05144386 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: EBT-101-001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

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).

Conditions

HIV-1-infection

Keywords

CRISPR; Gene Therapy; AAV9; HIV; SaCas9

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of EBT-101

  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

  48 weeks

Study Arms (2)

EBT-101 Dose-Level 1

EXPERIMENTAL

Cohort A: Participants will be administered dose-level 1 of EBT-101

Biological: EBT-101

EBT-101 Dose-Level 2

EXPERIMENTAL

Cohort B: Participants will be administered dose-level 2 of EBT-101

Biological: EBT-101

Interventions

EBT-101 BIOLOGICAL

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

EBT-101 Dose-Level 1; EBT-101 Dose-Level 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Cohorts A and B will enroll male adults (sex at birth)
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 70 years (both inclusive).
• Weight: Cohort A ≥55 and ≤110 kg, Cohort B ≥55 and ≤90 kg.
• Cohorts A and B will only enroll male subjects (sex at birth).
• Chronic HIV-1 with known subtype B infection
• On stable regimen defined as continuous ART suppressive treatment with HIV RNA level below the level of quantitation for \>1 years prior to screening
• Plasma HIV-1 RNA levels below the limit of quantitation during screening.
• Peripheral blood CD4 T cell count ≥500 cells/mm3 for at least 2 years prior to 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.

You may not qualify if:

• 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 prior to screening.
• Received in the preceding 12 months or HCP plans to prescribe long-acting injectable ART.
• 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.
• Known history and/or documented: pre-HIV treatment nadir CD4+ T cell count \<200 cells/mm3 or post-suppressive HIV treatment confirmed CD4+ T cell \<200 cells/mm3 prior to screening
• History of AIDS-defining opportunistic infection prior to screening.
• 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.
• Predefined abnormal laboratory values within 42 days of dosing per protocol
• Known history of positive tuberculin skin test.
• Receipt of any investigational HIV vaccine (prophylactic and/or therapeutic) within the year prior to screening.

Sponsors & Collaborators

• Excision BioTherapeutics: lead

Study Sites (3)

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Cooper Health

Camden, New Jersey, 08103, United States

Location

Study Officials

• William Kennedy, MD

  Excision BioTherapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 3, 2021
• Study Start: January 24, 2022
• Primary Completion: November 14, 2024
• Study Completion: November 14, 2024
• Last Updated: December 2, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)