HIV-1-infectionPhase 1NCT05700630
Ph1 Study of FT538 Alone and With Vorinostat for Persistent Low-Level HIV Viremia
A Phase 1 study testing FT538 and Vorinostat in people with HIV-1-infection and ART, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
This is a single center Phase I clinical trial of FT538 administered intravenously (IV) once every 14 days for 4 consecutive doses for the reduction of the HIV reservoir in lymphoid tissue of HIV-infected individuals receiving standard of care (SOC) antiretroviral therapy (ART). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV-1-infection, ART, Cd4+ Lymphocyte Deficiency
- What is being tested?
- FT538 and Vorinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2024to 21 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, age ≥18 and ≤65 years at the time of signing the consent form
- HIV-1 infection on continuous antiretroviral therapy (ART) for at least 12 months without any interruptions of greater than 14 consecutive days and without plans to modify ART before the End of Treatment visit.
- Two or more consecutive detectable HIV RNA levels of ≤200 copies/mL in the last 2 years, with at least one determination meeting this criterion in the previous 12 months. (If testing was not obtained within 42 days of planned dose 1, test will be repeated during subject screening to confirm status)
- Screening CD4+ T cell count ≥350 cells/ µl within 28 days of the 1st dose of FT538.
- Completion of initial COVID-19 vaccination series and/or documented COVID-19 infection with completion of treatment ≥ 3 months prior
- Patient weight of ≥ 50 kg due to FT538 fixed cell dosing and FT538 product pre-dosed packaging.
Show all 17Show fewer
- Adequate organ function within 14 days of Day 1, defined as the following:
- Platelet counts >150,000/mm^3
- Hemoglobin > 12.5 g/dL for men and > 11.5 g/dL for women. It is not acceptable for patients to be transfused within the prior month to meet this requirement. The use of Epogen is permitted.
- AST and ALT ≤ 3 x upper limit of institutional normal
- Estimated CrCl (eGFR) >50 mL/min/1.73m^2
- Persons of childbearing potential or with partners of childbearing potential must be willing to abstain from heterosexual activity or to use a highly effective form of contraception from the time of study enrollment through at least 4 months after the last dose of FT538. Persons are considered of childbearing potential unless: they are postmenopausal; are surgically sterile; or they have a congenital or acquired condition that prevents childbearing. NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception.
- For Dose Cohort 4 (FT538 plus Vorinostat):
- Females of childbearing potential must use highly effective contraception from the time of study enrollment through 6 months after the last dose of vorinostat.
- Males with partners of childbearing potential must use highly effective contraception from the time of study enrollment through 3 months after the last dose of vorinostat or 4 months after the last dose of FT538, whichever is more conservative.
- Must agree to and sign the consent for the Master Long-Term Follow-Up study to fulfill the FDA recommended 15 years following exposure to the investigational gene therapy product.
- Voluntary written consent prior to the performance of any research related procedures.
Who cannot join
- Pregnant, breastfeeding, or unwilling to practice birth control for a minimum of 4 months after the last dose of FT538. If of childbearing potential, a negative pregnancy test is required within 14 days prior to the 1st dose of FT538 or within 7 days prior to the 1st dose of vorinostat if treated in Dose Cohort 4.
- Known allergy to the following FT538 components: albumin (human) or DMSO.
- Currently receiving or likely to require systemic immunosuppressive therapy (e.g., prednisone >5 mg daily) for any reason within 5 days before the 1st dose of FT538 and 14 days after the last dose of FT538 - inhaled and topical steroids are permitted.
- Active or recent malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months - minor surgical removal of localized skin cancers (squamous cell carcinoma, basal cell carcinoma) is permitted.
- Prior history of solid organ transplant or hematopoietic stem cell transplant.
- Receipt of any investigational agent (not approved by the FDA for any indication) within 28 days prior to the first dose of FT538. Note that participation in prior HIV cure studies, including those involving IL-2 or N803, is permitted as long as experimental therapy completed >28 days prior.
Show all 19Show fewer
- Chronic liver disease defined as Class B and C on the Child-Pugh scale.
- Active and poorly controlled atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 ACC/AHA guidelines, including a previous diagnosis of any of the following within the previous 12 months: (a) acute myocardial infarction, (b) acute coronary syndromes, (c) stable or unstable angina, (d) coronary or other arterial revascularization, (e) stroke, (f) transient ischemic attack (TIA), or (g) peripheral arterial disease presumed to be of atherosclerotic origin.
- Moderate-severe obstructive lung disease. In subjects reporting a history of mild obstructive lung disease at screening, pulmonary function test (PFT) to be obtained and patient excluded from study if the FEV1 is <80% of predicted.
- Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment.
- Known concurrent or recent (defined as having received treatment within the last 3 months) infection with:
- Latent or active TB infection prior to completing a standard regimen of anti-TB therapy; defined as meeting PPD criteria for TB exposure or a positive quantiferon gold test collected at screening
- Active fungal infection requiring systemic antifungal therapy
- Chronic active hepatitis B or C. For Hepatitis B this will be defined as HBs antigen + and for Hepatitis C this will be defined as Hepatitis C antibody positive and Hepatitis C PCR+.
- COVID-19; defined as a positive SARS-CoV-2 PCR test at screening or a history of COVID-19 diagnosed within the last 3 months.
- Clinical vaccination administered within 6 weeks of the 1st dose of FT538.
- Presence of any social issues that, per investigator judgement, are likely to interfere with study conduct or may cause increased risk to patient.
- Patient history of alcohol or substance abuse that, per investigator judgement, are likely to interfere with study conduct or may cause increased risk to patient
- Any medical condition or clinical laboratory abnormality that, per investigator judgement, precludes safe participation in and completion of the study or that could affect compliance with protocol conduct or interpretation of results.
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: MT2022-06: Phase I Study of FT538 Monotherapy and in Combination With Vorinostat for the Treatment of Persistent Low-Level HIV Viremia
This is a single center Phase I clinical trial of FT538 administered intravenously (IV) once every 14 days for 4 consecutive doses for the reduction of the HIV reservoir in lymphoid tissue of HIV-infected individuals receiving standard of care (SOC) antiretroviral therapy (ART). As this is an early 1st in human study and the 1st for HIV-infected individual, the safety of FT538 is confirmed prior to the addition of oral vorinostat to explore the concept of "Kick and Kill".
- Being tested
- FT538, Vorinostat
- Keywords
- FT538, ACC/AHA, ADCC, AE, AIDS, ASCVD, CAR, CFR, CIBMTR, CLIA, CNS, CRP, CRS, CSRC, DC, DLT, GALT, HDACi, HIV, ICANS
- Medical subject headings
- Cd4+ Lymphocyte Deficiency, Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FT538Biological
FT538 is an investigational off-the-shelf cryopreserved NK cell product derived from an iPSC that contains three functional modifications: 1) a novel high affinity, non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface and remains fully functional after NK cell activation, thus augmenting ADCC; 2) an IL-15 receptor fusion that promotes NK cell activity and enhances cell persistence; and 3) the knock-out of CD38 expression prevent anti-CD38 antibody-induced fratricide.
VorinostatDrug
Vorinostat is a histone deacetylase inhibitor (HDACi) that is FDA approved for the treatment of cutaneous T-cell lymphoma and, under investigation in HIV as disruptor of HIV latency.
| Study group | Role | What they receive |
|---|---|---|
| Determine the safety and feasibility of administering FT538 monotherapy | Experimental | Administering FT538 monotherapy as an intravenous infusion once every 14 days for 4 consecutive doses and in combination with twice weekly vorinostat for the reduction of the HIV reservoir. Receives: Biological: FT538 |
| Characterize the toxicities and impact of FT538 and vorinostat | Experimental | To characterize the toxicities associated with FT538 monotherapy and with vorinostat in this patient population. To determine the impact of FT538 on the persistence of low-level HIV viremia, defined as detectable HIV-1 RNA of ≤200 copies/mL despite good ART adherence. Receives: Biological: FT538; Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety and feasibility of administering FT538 monotherapy.
At screen and baseline visits, all grades of signs and symptoms that occurred 30 days prior to the visit will be recorded. At all subsequent visits, all grades of signs and symptoms that occurred since the previous visit must be recorded as part of an Adverse Event (AE) assessment.
Measured: 26 months
Secondary outcomes (2)
Characterize the toxicities associated with FT538 monotherapy and vorinostat.
flow cytometric analysis for NK cell degranulation (CD107a).
Measured: 30 months
Determine the impact of FT538 on the persistence of low-level HIV viremia
Defined as patients with detectable HIV-1 RNA of ≤200 copies/mL despite good ART adherence.
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2023
- Study start15 Jul 2024 (estimated)
- Primary completion26 Jul 2024 (estimated)
- Study completion21 Aug 2024 (estimated)
Why it stopped: Abandoned
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05700630
- Sponsor's protocol ID
- 2022LS028
- Status last verified
- Feb 2024
- First submitted
- 9 Dec 2022
- Last updated
- 26 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Research related samples will be managed using established protocols in the Schacker Laboratory.
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MT2022-06: Phase I Study of FT538 Monotherapy and in Combination With Vorinostat for the Treatment of Persistent Low-Level HIV Viremia
- ClinicalTrials.gov ID
- NCT05700630
- Acronym / sponsor ID
- 2022LS028
- Keywords
- FT538, ACC/AHA, ADCC, AE, AIDS, ASCVD, CAR, CFR
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Abandoned
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 15 Jul 2024 (estimated)
- Primary completion
- 26 Jul 2024 (estimated)
- Study completion
- 21 Aug 2024 (estimated)
- First posted
- 26 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single center Phase I clinical trial of FT538 administered intravenously (IV) once every 14 days for 4 consecutive doses for the reduction of the HIV reservoir in lymphoid tissue of HIV-infected individuals receiving standard of care (SOC) antiretroviral therapy (ART). As this is an early 1st in human study and the 1st for HIV-infected individual, the safety of FT538 is confirmed prior to the addition of oral vorinostat to explore the concept of "Kick and Kill".
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Determine the safety and feasibility of administering FT538 monotherapy | Experimental | Biological: FT538Administering FT538 monotherapy as an intravenous infusion once every 14 days for 4 consecutive doses and in combination with twice weekly vorinostat for the reduction of the HIV reservoir. |
| Characterize the toxicities and impact of FT538 and vorinostat | Experimental | Biological: FT538, Drug: VorinostatTo characterize the toxicities associated with FT538 monotherapy and with vorinostat in this patient population. To determine the impact of FT538 on the persistence of low-level HIV viremia, defined as detectable HIV-1 RNA of ≤200 copies/mL despite good ART adherence. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female, age ≥18 and ≤65 years at the time of signing the consent form
- HIV-1 infection on continuous antiretroviral therapy (ART) for at least 12 months without any interruptions of greater than 14 consecutive days and without plans to modify ART before the End of Treatment visit.
- Two or more consecutive detectable HIV RNA levels of ≤200 copies/mL in the last 2 years, with at least one determination meeting this criterion in the previous 12 months. (If testing was not obtained within 42 days of planned dose 1, test will be repeated during subject screening to confirm status)
- Screening CD4+ T cell count ≥350 cells/ µl within 28 days of the 1st dose of FT538.
- Completion of initial COVID-19 vaccination series and/or documented COVID-19 infection with completion of treatment ≥ 3 months prior
Key exclusion criteria (19 listed)
- Pregnant, breastfeeding, or unwilling to practice birth control for a minimum of 4 months after the last dose of FT538. If of childbearing potential, a negative pregnancy test is required within 14 days prior to the 1st dose of FT538 or within 7 days prior to the 1st dose of vorinostat if treated in Dose Cohort 4.
- Known allergy to the following FT538 components: albumin (human) or DMSO.
- Currently receiving or likely to require systemic immunosuppressive therapy (e.g., prednisone >5 mg daily) for any reason within 5 days before the 1st dose of FT538 and 14 days after the last dose of FT538 - inhaled and topical steroids are permitted.
- Active or recent malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months - minor surgical removal of localized skin cancers (squamous cell carcinoma, basal cell carcinoma) is permitted.
- Prior history of solid organ transplant or hematopoietic stem cell transplant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FT538FT538 is an investigational off-the-shelf cryopreserved NK cell product derived from an iPSC that contains three functional modifications: 1) a novel high affinity, non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface and remains fully functional after NK cell activation, thus augmenting ADCC; 2) an IL-15 receptor fusion that promotes NK cell activity and enhances cell persistence; and 3) the knock-out of CD38 expression prevent anti-CD38 antibody-induced fratricide. | Biological | Characterize the toxicities and impact of FT538 and vorinostat, Determine the safety and feasibility of administering FT538 monotherapy |
| VorinostatVorinostat is a histone deacetylase inhibitor (HDACi) that is FDA approved for the treatment of cutaneous T-cell lymphoma and, under investigation in HIV as disruptor of HIV latency. | Drug | Characterize the toxicities and impact of FT538 and vorinostat |
Primary outcome
Determine the safety and feasibility of administering FT538 monotherapy.
Time frame: 26 months
At screen and baseline visits, all grades of signs and symptoms that occurred 30 days prior to the visit will be recorded. At all subsequent visits, all grades of signs and symptoms that occurred since the previous visit must be recorded as part of an Adverse Event (AE) assessment.
2 secondary outcomes
Characterize the toxicities associated with FT538 monotherapy and vorinostat.
Time frame: 30 months
Determine the impact of FT538 on the persistence of low-level HIV viremia
Time frame: 30 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2024.
- Individual participant dataSharing planned: No. Research related samples will be managed using established protocols in the Schacker Laboratory.
Related trials for HIV-1-infection
RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
HIV (Human Immunodeficiency Virus), Pregnancy
RecruitingPhase 4
A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments
HIV-1-infection
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
Active, not recruitingPhase 3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With Biktarvy
HIV-1-infection
Active, not recruitingPhase 2/3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With a Complicated Regimen (ARTISTRY-1)
HIV-1-infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FT538 and Vorinostat in people with HIV-1-infection and ART, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the safety and feasibility of administering FT538 monotherapy. (time frame: 26 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2024.