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

• ClinicalTrials.gov Identifier: NCT05144386
• Recruitment Status: Recruiting
• First Posted: December 3, 2021
• Last Update Posted: November 7, 2023
• Sponsor: Excision BioTherapeutics
• Information provided by (Responsible Party): Excision BioTherapeutics

Tracking Information

• First Submitted Date: November 22, 2021
• First Posted Date: December 3, 2021
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: January 24, 2022
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 22, 2021)

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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1-infection

Intervention

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

Study Arms

• Experimental: EBT-101 Dose-Level 1
  Cohort A: Participants will be administered dose-level 1 of EBT-101
  Intervention: Biological: EBT-101
• Experimental: EBT-101 Dose-Level 2
  Cohort B: Participants will be administered dose-level 2 of EBT-101
  Intervention: Biological: EBT-101
• Experimental: EBT-101 Dose-Level 3
  Cohort C: Participants will be administered dose-level 3 of EBT-101
  Intervention: Biological: EBT-101

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 22, 2021): 9
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

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).
• Body weight ≥55 and ≤110 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.
• 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 pre-HIV treatment nadir CD4 T cell count <200 cells/mm3 or post-HIV treatment confirmed CD4+ <200 cells/mm3.
• 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.
• Abnormal laboratory values in hematology, hepatic, renal, peripheral blood CD4 T cell count <500 cells/mm3, and other systems for lab safety screening.
• 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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Cohorts A and B will enroll male adults (sex at birth)

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: William Kennedy, MD; 833-214-2241; clinicalscience@excisionbio.com

Contact: Study Lead at ExcisionBio; clinicalscience@excisionbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05144386
• Other Study ID Numbers: EBT-101-001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Excision BioTherapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Excision BioTherapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: William Kennedy, MD; Excision BioTherapeutics

• PRS Account: Excision BioTherapeutics
• Verification Date: November 2023