Human Immunodeficiency VirusPhase 1/2NCT02648516
Safety and Efficacy of Allogenic Adoptive Immune Therapy for Immune Reconstitution in Chronic HIV-1 Infected Patients
A Phase 1/2 study testing Conventional plus AAIT in people with Human Immunodeficiency Virus and Disorder of Immune Reconstitution, run by Beijing 302 Hospital at 1 site in China.
Trial summary
Combination antiretroviral therapy (ART) effectively suppresses viral replication, leading to a significant immune recovery and a dramatic reduction in the incidence of AIDS-defining events. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Human Immunodeficiency Virus, Disorder of Immune Reconstitution
- What is being tested?
- Conventional plus AAIT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Oct 2016to Dec 2022
- Phase
- Phase 1/2
- 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
- Immune non-responders with chronic HIV-1 infection
- Antiretroviral therapy (ART) for at least 24 months prior to study entry and continue within the 24 months after study entry
- CD4 count less than or equal to 200 cells/mm3 continuously and more than 50 cells/mm3 before entry and at screening, obtained within 30 days prior to study entry
- Viral load less than or equal to 50 copies/mL obtained within 12 months prior to study entry
- Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol
- Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained
Show all 9Show fewer
- No history of Centers for Disease Control and Prevention (CDC) category C AIDS-related opportunistic infections
- Karnofsky performance score greater than or equal to 70 within 30 days prior to study entry
- Ability and willingness to provide informed consent
Who cannot join
- Coinfection with other virus, including serum hepatitis C virus RNA positive, or one of followings are positive in anti-hepatitis A virus/anti-HDV/anti-hepatitis delta virus plus alanine aminotransferase (ALT) more than 80 IU/L
- History of combination with other severe diseases including renal, circulatory, respiratory, digestive, endocrine, neural and immunological diseases and tumors
- White blood cell (WBC) <2.5*10E9/L, platlet counts <50*10E9/L, Hb <80g/L, lactate >2 mmol/L
- Allergic constitution
- Pregnancy or lactation
- Accepting other immunomodulatory drugs within 6 months prior screening
- Drug addiction
- Other conditions possibly influencing the trial
Trial locations and contacts
1 site in 1 country.
Fu-Sheng Wang contact
Yan-Mei Jiao contact
China1 site, 1 recruiting
- Recruiting
Beijing 302 hospital
Beijing, Beijing Municipality, 100069
Ji-yuan Zhang, PhD
Yan-mei Jiao, PhD
About this study
Official title: Safety and Efficacy of Allogenic Adoptive Immune Therapy for Immune Reconstitution Failure in Chronic HIV-1 Infected Patients
Combination antiretroviral therapy (ART) effectively suppresses viral replication, leading to a significant immune recovery and a dramatic reduction in the incidence of AIDS-defining events. However, approximately 20% of individuals who exhibit stable viral suppression by ART, but fail to achieve sufficient immune reconstitution and are considered immune nonresponders (INRs). These INRs often experience an increased risk of opportunistic infections and shorter life expectancy compared with matched immune responders.Therefore, efficiently treating these immune nonresponders has become one of the most difficult challenges in the clinic.
Read the detailed description
There is not a consensus definition of immunologic nonresponder individuals. In this study, we described patients whose cluster of differentiation 4（CD4)+ T-cell count remained below 200 cells/ul after 2 years of effective antiviral as immunologic nonresponders, in which viroimmunological dissociation implies a greater risk of AIDS related and non-AIDS-related illnesses. Immune-based therapy such as interleukin (IL)-2 and IL-7 have been shown to increase CD4 T-cell counts but yielded no clinical benefit in a large randomized study. We have reported that umbilical cord Tissue Mesenchymal Stem Cells (UC-MSC) treatment is safe and can significantly decrease systemic immune overactivation and improve immune reconstitution in INR patients. Meanwhile, we did not find that there was a significantly transitory increase in peripheral CD4 T-cell counts within 1-2 weeks since the onset of each MSC infusion. More important, umbilical cord-MSCs were found to be with a potential to produce IL-7 and T-cell growth factor transforming growth factor (TGF)-β in vitro and in vivo and preferentially expand CD4 T-cell response in the recipients. Therefore, development of novel interventions to reduce immune overactivation/inflammation and enhance immune reconstitution in INRs is a high priority.
Granulocyte colony-stimulating factor (G-CSF)-mobilized donor peripheral blood mononuclear cells (MNCs) are a heterogeneous population of immune cells that have a potential role in immunomodulation and hemopoiesis. Here, we hypothesized that human leukocyte antigen (HLA)-mismatched MNCs transfusion can be used to comprehensively restore or boost the host holistic immune system for INR patients, to the degree similar as immune responders.
The purpose of this study is to investigate the safety and initial efficacy of allogeneic adoptive immune therapy (AAIT) for INR patients. 20 INR patients received i.v. transfusion one round (3 times) of 2.0-3.0*10E8 cells/kg of MNCs as the treated group. All of them received the conventional treatment for AIDS. The CD4 T cell numbers, HIV reservoir, side effects, symptom improvement, control of opportunistic infections and will be evaluated during the 96-week follow up.
- Being tested
- Conventional plus AAIT
- Keywords
- Immune Reconstitution, Allogenic HLA-Mismatched Mononuclear Cells Transplantation
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional plus AAITCombination product
Also called Conventional plus allogenic adoptive immune treatment
Participants will receive ART and taken i.v., at a dose of 2-3*10E8 MNCs/kg body at baseline, week 1 and 2.
| Study group | Role | What they receive |
|---|---|---|
| Conventional plus AAIT | Experimental | Participants will receive ART plus a dose of allogenic adoptive immune transfusion (3 times of MNCs transfusions) from day 0 through the week 2 study visit. Receives: Combination Product: Conventional plus AAIT |
What is being measured
The primary outcome is the main question the study is designed to answer.
The changes of CD4 T cell counts
marker for host immunity
Measured: At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Secondary outcomes (3)
The changes of HIV-1 DNA
marker for HIV-1 reservoir
Measured: At Baseline and up to week 96
The ratio of CD4 and CD8 T cells
marker for host immunity
Measured: At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
marker for safety
Measured: At Baseline and up to week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2016 (estimated)
- Study startOct 2016
- Primary completionJul 2021 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency VirusStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing 302 Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wang Fu-Sheng, Principal investigator, Beijing 302 Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02648516
- Sponsor's protocol ID
- Beijing302-010
- Status last verified
- May 2019
- First submitted
- 8 Sep 2015
- Last updated
- 19 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Zhang Z, Fu J, Xu X, Wang S, Xu R, Zhao M, Nie W, Wang X, Zhang J, Li T, Su L, Wang FS. Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients. AIDS. 2013 May 15;27(8):1283-93. doi: 10.1097/QAD.0b013e32835fab77.
PubMed 23925377Hutter G. Stem cell transplantation in strategies for curing HIV/AIDS. AIDS Res Ther. 2016 Sep 13;13(1):31. doi: 10.1186/s12981-016-0114-y. eCollection 2016.
PubMed 27625700Corbeau P, Reynes J. Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection. Blood. 2011 May 26;117(21):5582-90. doi: 10.1182/blood-2010-12-322453. Epub 2011 Mar 14.
PubMed 21403129
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Allogenic Adoptive Immune Therapy for Immune Reconstitution Failure in Chronic HIV-1 Infected Patients
- ClinicalTrials.gov ID
- NCT02648516
- Acronym / sponsor ID
- Beijing302-010
- Keywords
- Immune Reconstitution, Allogenic HLA-Mismatched Mononuclear Cells Transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Beijing 302 HospitalUniversity, hospital or other
- Study start
- Oct 2016 (actual)
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 7 Jan 2016 (estimated)
- 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.
Combination antiretroviral therapy (ART) effectively suppresses viral replication, leading to a significant immune recovery and a dramatic reduction in the incidence of AIDS-defining events. However, approximately 20% of individuals who exhibit stable viral suppression by ART, but fail to achieve sufficient immune reconstitution and are considered immune nonresponders (INRs). These INRs often experience an increased risk of opportunistic infections and shorter life expectancy compared with matched immune responders.Therefore, efficiently treating these immune nonresponders has become one of the most difficult challenges in the clinic.
Detailed description
There is not a consensus definition of immunologic nonresponder individuals. In this study, we described patients whose cluster of differentiation 4（CD4)+ T-cell count remained below 200 cells/ul after 2 years of effective antiviral as immunologic nonresponders, in which viroimmunological dissociation implies a greater risk of AIDS related and non-AIDS-related illnesses. Immune-based therapy such as interleukin (IL)-2 and IL-7 have been shown to increase CD4 T-cell counts but yielded no clinical benefit in a large randomized study. We have reported that umbilical cord Tissue Mesenchymal Stem Cells (UC-MSC) treatment is safe and can significantly decrease systemic immune overactivation and improve immune reconstitution in INR patients. Meanwhile, we did not find that there was a significantly transitory increase in peripheral CD4 T-cell counts within 1-2 weeks since the onset of each MSC infusion. More important, umbilical cord-MSCs were found to be with a potential to produce IL-7 and T-cell growth factor transforming growth factor (TGF)-β in vitro and in vivo and preferentially expand CD4 T-cell response in the recipients. Therefore, development of novel interventions to reduce immune overactivation/inflammation and enhance immune reconstitution in INRs is a high priority.
Granulocyte colony-stimulating factor (G-CSF)-mobilized donor peripheral blood mononuclear cells (MNCs) are a heterogeneous population of immune cells that have a potential role in immunomodulation and hemopoiesis. Here, we hypothesized that human leukocyte antigen (HLA)-mismatched MNCs transfusion can be used to comprehensively restore or boost the host holistic immune system for INR patients, to the degree similar as immune responders.
The purpose of this study is to investigate the safety and initial efficacy of allogeneic adoptive immune therapy (AAIT) for INR patients. 20 INR patients received i.v. transfusion one round (3 times) of 2.0-3.0*10E8 cells/kg of MNCs as the treated group. All of them received the conventional treatment for AIDS. The CD4 T cell numbers, HIV reservoir, side effects, symptom improvement, control of opportunistic infections and will be evaluated during the 96-week follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Conventional plus AAIT | Experimental | Combination Product: Conventional plus AAITParticipants will receive ART plus a dose of allogenic adoptive immune transfusion (3 times of MNCs transfusions) from day 0 through the week 2 study visit. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Immune non-responders with chronic HIV-1 infection
- Antiretroviral therapy (ART) for at least 24 months prior to study entry and continue within the 24 months after study entry
- CD4 count less than or equal to 200 cells/mm3 continuously and more than 50 cells/mm3 before entry and at screening, obtained within 30 days prior to study entry
- Viral load less than or equal to 50 copies/mL obtained within 12 months prior to study entry
- Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol
Key exclusion criteria (8 listed)
- Coinfection with other virus, including serum hepatitis C virus RNA positive, or one of followings are positive in anti-hepatitis A virus/anti-HDV/anti-hepatitis delta virus plus alanine aminotransferase (ALT) more than 80 IU/L
- History of combination with other severe diseases including renal, circulatory, respiratory, digestive, endocrine, neural and immunological diseases and tumors
- White blood cell (WBC) <2.5*10E9/L, platlet counts <50*10E9/L, Hb <80g/L, lactate >2 mmol/L
- Allergic constitution
- Pregnancy or lactation
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 |
|---|---|---|
| Conventional plus AAITAlso: Conventional plus allogenic adoptive immune treatmentParticipants will receive ART and taken i.v., at a dose of 2-3*10E8 MNCs/kg body at baseline, week 1 and 2. | Combination product | Conventional plus AAIT |
Primary outcome
The changes of CD4 T cell counts
Time frame: At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
marker for host immunity
3 secondary outcomes
The changes of HIV-1 DNA
Time frame: At Baseline and up to week 96
The ratio of CD4 and CD8 T cells
Time frame: At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: At Baseline and up to week 96
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2019.
- Background: PubMed 23925377Zhang Z, Fu J, Xu X, Wang S, Xu R, Zhao M, Nie W, Wang X, Zhang J, Li T, Su L, Wang FS. Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients. AIDS. 2013 May 15;27(8):1283-93. doi: 10.1097/QAD.0b013e32835fab77.
- Background: PubMed 27625700Hutter G. Stem cell transplantation in strategies for curing HIV/AIDS. AIDS Res Ther. 2016 Sep 13;13(1):31. doi: 10.1186/s12981-016-0114-y. eCollection 2016.
- Background: PubMed 21403129Corbeau P, Reynes J. Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection. Blood. 2011 May 26;117(21):5582-90. doi: 10.1182/blood-2010-12-322453. Epub 2011 Mar 14.
- 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.
Fu-Sheng Wang contact
Yan-Mei Jiao contact
Wang Fu-Sheng principal investigator
Beijing 302 Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Conventional plus AAIT in people with Human Immunodeficiency Virus and Disorder of Immune Reconstitution, 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 9 inclusion and 8 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 19 Jun 2019. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Fu-Sheng Wang (fswang302@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The changes of CD4 T cell counts (time frame: At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96). 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 NCT02648516, which also lists 3 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 19 Jun 2019.