Clinical trial NCT05144386: Study of EBT-101 in Aviremic HIV-1 Infected Adults on Stable ART
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1-infection
Keywords: CRISPR
Gene Therapy
AAV9
HIV
SaCas9
Lead sponsor: Excision BioTherapeutics
Sponsor class: INDUSTRY
First posted: 2021-12-03
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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 after Week 12 for ATI participants. Non-ATI participants are followed monthly 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 is 15 years.

Eligibility 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 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.

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 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.
* 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.

Primary outcomes:
measure: Safety and Tolerability of EBT-101
timeFrame: 48 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Camden
country: United States
facility: Cooper Health
state: New Jersey
Study officials:
affiliation: Excision BioTherapeutics
name: William Kennedy, MD
role: STUDY_DIRECTOR
References: