EBT-101 for HIV

No longer recruiting at 7 trial locations

Overseen By William Kennedy, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Excision BioTherapeutics

Must be taking: Antiretrovirals

Must not be taking: Injectable ART

Disqualifiers: HIV dementia, Cardiac disease, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EBT-101 for individuals with HIV who currently control the virus with antiretroviral therapy (ART). The study evaluates the safety and effectiveness of EBT-101 when administered intravenously, with participants receiving one of two different dose levels. It specifically targets men with HIV-1, subtype B, who have managed the virus well with ART for over a year and have no detectable virus in their blood. Participants should also have a healthy immune cell count (CD4 T cells) and be willing to stop ART if eligible. This trial helps researchers learn more about potential new treatments for HIV. As a Phase 1 trial, this research focuses on understanding how EBT-101 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable antiretroviral therapy (ART) regimen before joining, and they must be willing to stop ART if eligible for a treatment interruption. The protocol does not specify stopping other medications.

Is there any evidence suggesting that EBT-101 is likely to be safe for humans?

Research has shown that EBT-101 is generally safe for people. In earlier studies, participants did not experience serious side effects or reach unsafe dose levels, indicating that the treatment did not cause harm at the doses tested. Additionally, EBT-101 was well-tolerated, with no major issues reported by participants. Although the treatment did not cure HIV or prevent the virus from returning, its safety record was positive. This suggests that EBT-101, which uses a new method called CRISPR-based gene editing, might be safe to try in this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

EBT-101 is unique because it utilizes CRISPR gene-editing technology to target and potentially remove the HIV genome from infected cells, a groundbreaking approach compared to current antiretroviral therapies that only suppress the virus. Most treatments for HIV, like antiretroviral drugs, work by keeping the virus at bay, requiring lifelong adherence to medication. Researchers are excited about EBT-101 because it offers the potential for a one-time treatment that could result in a functional cure, meaning the virus could be controlled without continuous medication. This innovative method represents a significant shift in how HIV might be managed in the future.

What evidence suggests that EBT-101 might be an effective treatment for HIV?

Research has shown that EBT-101, a new gene therapy using CRISPR technology, has produced promising early results for treating HIV. In one case, a participant controlled the virus for 16 weeks after stopping regular medication, exceeding expectations. This suggests that EBT-101 might manage the virus more effectively than current treatments alone. However, in other cases, the virus returned. The treatment has proven safe, which encourages further research. Participants in this trial will receive varying doses of EBT-101 to further evaluate its effectiveness and safety. ^{3 4 5 6 7}

Who Is on the Research Team?

William Kennedy, MD

Principal Investigator

Excision BioTherapeutics

Are You a Good Fit for This Trial?

This trial is for aviremic HIV-1 infected males, aged 18-60, on stable ART for over 2 years with no breaks or changes in the last year. Participants must have undetectable viral loads, CD4 counts >500 cells/mm3, be vaccinated against N. meningitidis and COVID-19, and willing to potentially stop ART.

Inclusion Criteria

My weight is between 55 and 110 kg.

I have completed the COVID-19 vaccination series and boosters as recommended, with the last dose taken at least 30 days ago.

I am a male by birth.

Exclusion Criteria

I have been diagnosed with liver cirrhosis.

I have had HIV-related memory or thinking problems.

Evidence of acute or chronic hepatitis B and/or hepatitis C

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Several visits

Treatment

Participants receive a single IV dose of EBT-101 on Day 1

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored daily for the first 14 days post-treatment

2 weeks

Daily visits (in-person)

Analytical Treatment Interruption (ATI) Follow-up

Participants eligible for ATI are monitored weekly after Week 12

36 weeks

Weekly visits (in-person)

Non-ATI Follow-up

Non-ATI participants are followed monthly after Week 12

36 weeks

Monthly visits (in-person)

Long Term Follow Up (LTFU)

Participants are enrolled in a separate LTFU study for safety monitoring

15 years

What Are the Treatments Tested in This Trial?

Interventions

• EBT-101

Trial Overview EBT-101 is being tested as a new treatment option for HIV. It's given intravenously to adults who are already on antiretroviral therapy (ART) that keeps their virus levels low. The study will monitor how well EBT-101 works and its safety.

How Is the Trial Designed?

Group I: EBT-101 Dose-Level 2 Experimental Treatment 1 Intervention

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

Group II: EBT-101 Dose-Level 1 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Excision BioTherapeutics

Lead Sponsor

Trials

2

Recruited

20+

Published Research Related to This Trial

The SCOLTA project has enrolled 1184 patients to monitor adverse reactions to new antiretroviral drugs, with a significant focus on lopinavir/ritonavir (LPV/r), which reported 73 out of 100 severe adverse events (grades III and IV).

The rate of adverse events in the LPV/r cohort was 14.2 per 100 person-years, indicating that this system provides valuable real-time data for assessing the safety and long-term toxicity of antiretroviral treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Italian approach to postmarketing monitoring: preliminary results from the SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) project on the safety of lopinavir/ritonavir. Bonfanti, P., Martinelli, C., Ricci, E., et al.[2022]

In a study of 1301 HIV-infected participants over a median follow-up of 5 years, significant differences in the risk of specific adverse events were observed based on gender and race, with black participants showing higher risks for cardiovascular and renal events, and women having a greater risk for anemia.

Despite these differences in specific adverse events, the overall rates of adverse events, all-cause mortality, and treatment discontinuations due to toxicity were similar across gender and racial groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethnicity, race, and gender. Differences in serious adverse events among participants in an antiretroviral initiation trial: results of CPCRA 058 (FIRST Study). Tedaldi, EM., Absalon, J., Thomas, AJ., et al.[2022]

In a study of 1160 patients on antiretroviral treatment for HIV-1, 47% experienced clinical adverse events and 27% had laboratory adverse events linked to their treatment, highlighting a significant prevalence of side effects.

The research found that more complex treatment regimens, such as dual-PI and three-class antiretroviral treatments, were associated with a higher likelihood of adverse events compared to simpler single-PI treatments, indicating the need for careful monitoring of patients on these regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study. Fellay, J., Boubaker, K., Ledergerber, B., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05144386

NCT05144386 | Study of EBT-101 in Aviremic HIV-1 ... 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.

2. excision.bio excision.bio/news/press-releases/detail/43/excision-biotherapeutics-announces-data-from-the-phase-12

Press Releases EBT-101 successfully met the primary endpoint of safety and secondary endpoint of biodistribution/immunogenicity in a Phase 1/2 study ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11697457/

The role of genetic diversity, epigenetic regulation, and sex ... The first-in-human clinical trial of Excision BioTherapeutics' CRISPR-based HIV cure, EBT-101, demonstrated safety but failed to prevent viral ...

4. aidsmap.com aidsmap.com/news/may-2024/crispr-gene-therapy-ebt-101-does-not-prevent-hiv-viral-rebound

CRISPR gene therapy EBT-101 does not prevent HIV viral ... One EBT-101 recipient was able to maintain viral suppression for 16 weeks after treatment discontinuation, considerably longer than it typically ...

5. eatg.org eatg.org/hiv-news/crispr-hiv-gene-therapy-disappoints-in-early-study/

CRISPR HIV gene therapy disappoints in early study One EBT-101 recipient was able to maintain viral suppression for four months after treatment discontinuation—considerably longer than it ...

6. excision.bio excision.bio/news/press-releases/detail/10/excision-biotherapeutics-presents-positive-interim-clinical

Press Releases Treatment with EBT-101 resulted in no serious adverse events or dose limiting toxicities in the first three participants, and all reported ...

7. crisprmedicinenews.com crisprmedicinenews.com/news/excisions-ebt-101-demonstrates-safety-in-clinical-trial-but-does-not-cure-hiv/

Excision's EBT-101 Demonstrates Safety in Clinical Trial ... Excision's EBT-101 Demonstrates Safety in Clinical Trial But Does Not Cure HIV. Clinical data presented at the ASGCT meeting in Baltimore ...