HIV-1Phase 1TCTIWHINCT04863066
Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection
A Phase 1 study testing CAR-T cells in people with HIV-1, run by Beijing 302 Hospital at 1 site in China.
Trial summary
To evaluate the safety of autologous CAR-T-cell therapy in individuals lived with HIV-1 infection, CAR T cells are infused after ex vivo expansion and transduction with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV-1
- What is being tested?
- CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2021to 1 Oct 2022
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 to 70 years
- HIV-1 infection by confirmed test;
- Receiving antiviral treatment ≥ 1 years;
- Current CD4+ T cell count > 350 cells/μl;
- HIV-1 RNA levels of < 50 copies/ml for at least a year;
- Patients who agrees to use two effective methods of contraception to avoid pregnancy during the study period.
- Patients who sign the informed consent form prior to inclusion in the study.
Who cannot join
- Patients with concomitant HAV, HBV, HCV, HDV, HEV, EBV, CMV or syphilis infection;
- A history of AIDS-related opportunistic infections and tumors within 1 year prior to enrollment;
- A History of corticosteroids or immunosuppressive drugs for autoimmune diseases by physicians within the last 2 years;
- Participants with clinically significant laboratory abnormalities as follows:
- Hemoglobin ≤ 10 gm/dl (female), <11g/dl (male)
- Absolute neutrophil count ≤ 1×10^9/L
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- Platelet count ≤100×10^9/L
- Alanine aminotransferase (ALT)≥ 2.5 x ULN
- Aspartate aminotransferase (AST) ≥ 2.5 x ULN
- Total bilirubin > 1.5 ULN
- Serum creatinine >110 μmol/L
- International normalized ratio (INR) >1.5 or activated partial thromboplastin time (APTT) >45 s
- Patients with severe psychiatric illness, drugs or alcohol abuse;
- A woman who is in pregnancy or lactation;
- A history of central nervous system disease, such as cerebral hemorrhage, dementia, epilepsy and autoimmune diseases;
- Patients with a non-AIDS-related serious underlying disease;
- Patients who participate in another clinical study currently which may affect the results of this study.
Trial locations and contacts
1 site in 1 country.
Xuanling Shi, MD contact
About this study
Official title: A Phase I Trial Using Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection
To evaluate the safety of autologous CAR-T-cell therapy in individuals lived with HIV-1 infection, CAR T cells are infused after ex vivo expansion and transduction with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody.
Read the detailed description
This study is a prospective, single-center, single-arm, open-label and phase I clinical trial. Subjects with CD4+T cell counts greater than 350/μl and viral loads of <50 copies/ml over 1 year by antiviral treatment are enrolled. T cells are stimulated with CD3 and CD28, transduced with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody and expanded for approximately 2 weeks. Then, patients are infused with CAR T cells at a dosage of 1×10^5 CAR-T cells/kg body weight. If this dose is well tolerated, dosing will be increased to 5×10^5 CAR T cells/kg body weight. After infusion, adverse events, and HIV-1 latent reservoir size and CAR levels in peripheral blood will be monitored to assess the safety of CAR-T-cell treatment, potential therapeutic efficacy and kinetics of CAR T cells.
- Conditions
- HIV-1
- Being tested
- CAR-T cells
- Keywords
- CAR T cells, HIV-1 infection, safety, HIV latent reservoir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-T cellsBiological
Also called HIV-1 specific chimeric antigen receptor T cells
The presence of latent infected cells remains a key barrier to HIV-1 functional cure. Current approach to reducing the latent HIV reservoir is to reactivate virus-containing cells to make them be detected and eliminated by host defense. Endogenous cytotoxic T-lymphocytes (CTL) may not be adequate because of cellular exhaustion and immune escape of virus. We have designed a kind of CAR-T cell based on CTL engineered to express a scFv of a broadly neutralizing anti-HIV antibody. According to our preclinical studies, CAR-T cells strongly eradicated HIV-1-infected target cells making them a particularly suitable candidate to reach a functional HIV cure. In this clinical trial, we mainly intend to evaluate the safety of CAR-T-Cell therapy on HIV patients whose plasma HIV has been successfully suppressed after antiviral therapy.
| Study group | Role | What they receive |
|---|---|---|
| CAR-T-cell therapy | Experimental | Four patients with plasma HIV RNA <50 copies/ml and CD4+T cell count more than 350 cells/μl receiving at least one-year antiviral treatment are injected intravenously with 1×10^5 CAR-T cells/kg body weight. If the dosage of 1×10^5 CAR-T cells/kg body weight is well tolerated, 5×10^5 CAR-T cells/kg body weight will be infused for another 4 subjects who meet the inclusion and exclusion criteria. Receives: Biological: CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation the safety of CAR-T-cell treatment
To assess the adverse events of CAR-T-cell therapy in HIV-1 infected individuals by measuring liver function, blood routine, and cytokine and so on in this clinical trial
Measured: 3 months
Secondary outcomes (1)
Assessment the potential therapeutic efficacy of CAR-T cell therapy
To evaluate the change of HIV-1 latent reservoir in peripheral blood after CAR-T-cell therapy by RT-PCR
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2021
- Study start1 May 2021 (estimated)
- Primary completion15 Jun 2022 (estimated)
- Study completion1 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV-1Studies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing 302 Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Tsinghua University
- Responsible party
- Sponsor
- Investigators
- Fu-Sheng Wang, MD, Principal investigator, Beijing 302 Hospital of China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04863066
- Sponsor's protocol ID
- 2020-HIV-001
- Acronym
- TCTIWHI
- Status last verified
- Oct 2020
- First submitted
- 7 Dec 2020
- Last updated
- 28 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Walker RE, Bechtel CM, Natarajan V, Baseler M, Hege KM, Metcalf JA, Stevens R, Hazen A, Blaese RM, Chen CC, Leitman SF, Palensky J, Wittes J, Davey RT Jr, Falloon J, Polis MA, Kovacs JA, Broad DF, Levine BL, Roberts MR, Masur H, Lane HC. Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood. 2000 Jul 15;96(2):467-74.
PubMed 10887107Mitsuyasu RT, Anton PA, Deeks SG, Scadden DT, Connick E, Downs MT, Bakker A, Roberts MR, June CH, Jalali S, Lin AA, Pennathur-Das R, Hege KM. Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects. Blood. 2000 Aug 1;96(3):785-93.
PubMed 10910888Abdel-Mohsen M, Richman D, Siliciano RF, Nussenzweig MC, Howell BJ, Martinez-Picado J, Chomont N, Bar KJ, Yu XG, Lichterfeld M, Alcami J, Hazuda D, Bushman F, Siliciano JD, Betts MR, Spivak AM, Planelles V, Hahn BH, Smith DM, Ho YC, Buzon MJ, Gaebler C, Paiardini M, Li Q, Estes JD, Hope TJ, Kostman J, Mounzer K, Caskey M, Fox L, Frank I, Riley JL, Tebas P, Montaner LJ; BEAT-HIV Delaney Collaboratory to Cure HIV-1 infection. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nat Med. 2020 Sep;26(9):1339-1350. doi: 10.1038/s41591-020-1022-1. Epub 2020 Sep 7.
PubMed 32895573Liu B, Zou F, Lu L, Chen C, He D, Zhang X, Tang X, Liu C, Li L, Zhang H. Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive Combined Antiretroviral Therapy. J Virol. 2016 Oct 14;90(21):9712-9724. doi: 10.1128/JVI.00852-16. Print 2016 Nov 1.
PubMed 27535056Maldini CR, Claiborne DT, Okawa K, Chen T, Dopkin DL, Shan X, Power KA, Trifonova RT, Krupp K, Phelps M, Vrbanac VD, Tanno S, Bateson T, Leslie GJ, Hoxie JA, Boutwell CL, Riley JL, Allen TM. Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo. Nat Med. 2020 Nov;26(11):1776-1787. doi: 10.1038/s41591-020-1039-5. Epub 2020 Aug 31.
PubMed 32868878
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial Using Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection
- ClinicalTrials.gov ID
- NCT04863066
- Acronym / sponsor ID
- TCTIWHI / 2020-HIV-001
- Conditions
- HIV-1
- Keywords
- CAR T cells, HIV-1 infection, safety, HIV latent reservoir
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- Beijing 302 HospitalUniversity, hospital or other
- Collaborators
- Tsinghua University
- Study start
- 1 May 2021 (estimated)
- Primary completion
- 15 Jun 2022 (estimated)
- Study completion
- 1 Oct 2022 (estimated)
- First posted
- 28 Apr 2021 (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.
To evaluate the safety of autologous CAR-T-cell therapy in individuals lived with HIV-1 infection, CAR T cells are infused after ex vivo expansion and transduction with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody.
Detailed description
This study is a prospective, single-center, single-arm, open-label and phase I clinical trial. Subjects with CD4+T cell counts greater than 350/μl and viral loads of <50 copies/ml over 1 year by antiviral treatment are enrolled. T cells are stimulated with CD3 and CD28, transduced with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody and expanded for approximately 2 weeks. Then, patients are infused with CAR T cells at a dosage of 1×10^5 CAR-T cells/kg body weight. If this dose is well tolerated, dosing will be increased to 5×10^5 CAR T cells/kg body weight. After infusion, adverse events, and HIV-1 latent reservoir size and CAR levels in peripheral blood will be monitored to assess the safety of CAR-T-cell treatment, potential therapeutic efficacy and kinetics of CAR T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-T-cell therapy | Experimental | Biological: CAR-T cellsFour patients with plasma HIV RNA <50 copies/ml and CD4+T cell count more than 350 cells/μl receiving at least one-year antiviral treatment are injected intravenously with 1×10^5 CAR-T cells/kg body weight. If the dosage of 1×10^5 CAR-T cells/kg body weight is well tolerated, 5×10^5 CAR-T cells/kg body weight will be infused for another 4 subjects who meet the inclusion and exclusion criteria. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged 18 to 70 years
- HIV-1 infection by confirmed test;
- Receiving antiviral treatment ≥ 1 years;
- Current CD4+ T cell count > 350 cells/μl;
- HIV-1 RNA levels of < 50 copies/ml for at least a year;
Key exclusion criteria (17 listed)
- Patients with concomitant HAV, HBV, HCV, HDV, HEV, EBV, CMV or syphilis infection;
- A history of AIDS-related opportunistic infections and tumors within 1 year prior to enrollment;
- A History of corticosteroids or immunosuppressive drugs for autoimmune diseases by physicians within the last 2 years;
- Participants with clinically significant laboratory abnormalities as follows:
- Patients with severe psychiatric illness, drugs or alcohol abuse;
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 |
|---|---|---|
| CAR-T cellsAlso: HIV-1 specific chimeric antigen receptor T cellsThe presence of latent infected cells remains a key barrier to HIV-1 functional cure. Current approach to reducing the latent HIV reservoir is to reactivate virus-containing cells to make them be detected and eliminated by host defense. Endogenous cytotoxic T-lymphocytes (CTL) may not be adequate because of cellular exhaustion and immune escape of virus. We have designed a kind of CAR-T cell based on CTL engineered to express a scFv of a broadly neutralizing anti-HIV antibody. According to our preclinical studies, CAR-T cells strongly eradicated HIV-1-infected target cells making them a particularly suitable candidate to reach a functional HIV cure. In this clinical trial, we mainly intend to evaluate the safety of CAR-T-Cell therapy on HIV patients whose plasma HIV has been successfully suppressed after antiviral therapy. | Biological | CAR-T-cell therapy |
Primary outcome
Evaluation the safety of CAR-T-cell treatment
Time frame: 3 months
To assess the adverse events of CAR-T-cell therapy in HIV-1 infected individuals by measuring liver function, blood routine, and cytokine and so on in this clinical trial
1 secondary outcome
Assessment the potential therapeutic efficacy of CAR-T cell therapy
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2021.
- Background: PubMed 10887107Walker RE, Bechtel CM, Natarajan V, Baseler M, Hege KM, Metcalf JA, Stevens R, Hazen A, Blaese RM, Chen CC, Leitman SF, Palensky J, Wittes J, Davey RT Jr, Falloon J, Polis MA, Kovacs JA, Broad DF, Levine BL, Roberts MR, Masur H, Lane HC. Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood. 2000 Jul 15;96(2):467-74.
- Background: PubMed 10910888Mitsuyasu RT, Anton PA, Deeks SG, Scadden DT, Connick E, Downs MT, Bakker A, Roberts MR, June CH, Jalali S, Lin AA, Pennathur-Das R, Hege KM. Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects. Blood. 2000 Aug 1;96(3):785-93.
- Background: PubMed 32895573Abdel-Mohsen M, Richman D, Siliciano RF, Nussenzweig MC, Howell BJ, Martinez-Picado J, Chomont N, Bar KJ, Yu XG, Lichterfeld M, Alcami J, Hazuda D, Bushman F, Siliciano JD, Betts MR, Spivak AM, Planelles V, Hahn BH, Smith DM, Ho YC, Buzon MJ, Gaebler C, Paiardini M, Li Q, Estes JD, Hope TJ, Kostman J, Mounzer K, Caskey M, Fox L, Frank I, Riley JL, Tebas P, Montaner LJ; BEAT-HIV Delaney Collaboratory to Cure HIV-1 infection. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nat Med. 2020 Sep;26(9):1339-1350. doi: 10.1038/s41591-020-1022-1. Epub 2020 Sep 7.
- Background: PubMed 27535056Liu B, Zou F, Lu L, Chen C, He D, Zhang X, Tang X, Liu C, Li L, Zhang H. Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive Combined Antiretroviral Therapy. J Virol. 2016 Oct 14;90(21):9712-9724. doi: 10.1128/JVI.00852-16. Print 2016 Nov 1.
- Results publication: PubMed 32868878Maldini CR, Claiborne DT, Okawa K, Chen T, Dopkin DL, Shan X, Power KA, Trifonova RT, Krupp K, Phelps M, Vrbanac VD, Tanno S, Bateson T, Leslie GJ, Hoxie JA, Boutwell CL, Riley JL, Allen TM. Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo. Nat Med. 2020 Nov;26(11):1776-1787. doi: 10.1038/s41591-020-1039-5. Epub 2020 Aug 31.
- Individual participant dataSharing planned: No
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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.
Xuanling Shi, MD contact
Fu-Sheng Wang, MD principal investigator
Beijing 302 Hospital of China
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 CAR-T cells in people with HIV-1, run by Beijing 302 Hospital at 1 site in China.
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 7 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 28 Apr 2021. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jinfang Zhao, MD (010-93332866, zhaojinfang13@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation the safety of CAR-T-cell treatment (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04863066, which also lists 5 linked publications.
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 28 Apr 2021.