MDR-TBPhase 4NCT05493267
A Exploratory Study of Vγ2Vδ2 T Lymphocyte-based Immunotherapy for MDR-TB
A Phase 4 study testing Vγ2Vδ2 T lymphocyte-based immunotherapy and Treatment regimens for MDR-TB in people with MDR-TB and Immunotherapy, run by Shanghai Pulmonary Hospital, Shanghai, China at 2 sites in China.
Trial summary
A Exploratory Study of drug combination (zoledronic acid/interleukin 2) that specifically amplifies Vγ2Vδ2 T cells in combination with anti-tuberculosis chemotherapy for the treatment of MDR-TB. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- MDR-TB, Immunotherapy
- What is being tested?
- Vγ2Vδ2 T lymphocyte-based immunotherapy and Treatment regimens for MDR-TB
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesChina
- Study dates
- 3 Aug 2022to 3 Aug 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- RR-TB/MDR-TB (resistant to at least isoniazid and rifampicin).
- Poor efficacy of the original treatment regimen or no response to treatment or less than 4 effective drugs.
Who cannot join
- Immunosuppression due to co-morbidities, such as immune system disorders, tumors, etc.
- Test confirms poor response to ZOL and IL-2 stimulation.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Shanghai Pulmonary Hospital, Shanghai, China
Shanghai, 200433
sha wei, +8602165115006 ext. 2017, 13671758200@126.com
liu yidian, +8602165115006 ext. 2011, 13816676933@139.com
- Recruiting
Shanghai Pulmonary Hospital
Shanghai
Liu yidian, +8602165115006 ext. 2017, 13816676933@139.com
About this study
A Exploratory Study of drug combination (zoledronic acid/interleukin 2) that specifically amplifies Vγ2Vδ2 T cells in combination with anti-tuberculosis chemotherapy for the treatment of MDR-TB.
Read the detailed description
The emergence and prevalence of drug-resistant TB in recent years has made TB control more challenging, and MDR-TB is more serious type of drug-resistance TB with a cure rate of just over half, even with the latest treatment regimens. Treatment modalities other than drugs should be considered for patients with drug-resistant TB who have poor treatment efficacy, for patients with drug-resistant TB who are unresponsive to treatment, and for other patients for whom an effective treatment regimen cannot be composed.
The human immune system plays an important role in the infection, development, treatment and regression of tuberculosis.Mtb is an intracellularly parasitic bacterium that evades host immune clearance.Immunotherapy for TB can kill intracellularly parasitic Mycobacterium tuberculosis, including drug-resistant Mycobacterium tuberculosis, by inducing a host-specific immune response.The combination of antituberculosis chemotherapy and immunotherapy has the potential to open up new avenues for the treatment of multidrug-resistant TB.
In recent years, several studies by our team and others addressing host immune mechanisms have shown that γδ T cells play an important role in the fight against TB infection.Vγ2Vδ2 T cells (also known as Vγ9Vδ2 T cells) are a specific subset of γδ T cells, the only γδ T cells capable of recognizing TB phosphoantigens, and are found only in human and non-human primates.
Our previous study demonstrated that zoledronic acid, an anti-osteoporotic and osteoprotective drug, induced the production of endogenous ligands for Vγ2Vδ2T cells and activated Vγ2Vδ2T cells. Zoledronic acid in combination with interleukin 2 can significantly expand Vγ2Vδ2T cells, and the expanded Vγ2Vδ2T cells can effectively kill intracellular parasitic Mycobacterium tuberculosis, it can also promote the production of more anti-tuberculosis effectors by Vγ2Vδ2T cells and widely stimulate the production of functional cytokines by CD4 and CD8 T cells.
The primate experiments conducted by our team in the ABSL-III laboratory of Wuhan University demonstrated that phosphoantigen/interleukin 2 in a macaque model of tuberculosis infection induced lung phosphoantigen-specific Vγ2Vδ2 T cell expansion and migration, reduced Mycobacterium tuberculosis load in vivo, and effectively improved immune resistance to tuberculosis lung necrosis, demonstrating that targeted Vγ2Vδ2 T cell Immunotherapy of Vγ2Vδ2 T cells has a significant therapeutic effect on TB infection in monkeys , and is also safe for use in macaques. Accordingly, the investigators propose a drug combination (zoledronic acid/interleukin 2) that specifically amplifies Vγ2Vδ2 T cells in combination with anti-tuberculosis chemotherapy for the treatment of multidrug-resistant tuberculosis.
- Conditions
- MDR-TB, Immunotherapy
- Being tested
- Vγ2Vδ2 T lymphocyte-based immunotherapy, Treatment regimens for MDR-TB
- Keywords
- MDR-TB；Immunotherapy；
- Medical subject headings
- Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vγ2Vδ2 T lymphocyte-based immunotherapyDrug
Also called Drug combination (zoledronic acid/interleukin 2)
Intravenous injection of zoledronic acid, followed by a subcutaneous injection recombinant human interleukin. Zoledronic acid was administered 3 times and recombinant human interleukin was administered 10 times for a total of 6 months.
Treatment regimens for MDR-TBDrug
Also called Treatment regimen for MDR-TB using WHO guidelines
Treatment regimens was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis.
| Study group | Role | What they receive |
|---|---|---|
| Vγ2Vδ2 T lymphocyte-based immunotherapy +Treatment regimens for MDR-TB | Experimental | Treatment was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis, with the addition of immunotherapy：zoledronic acid and recombinant human interleukin 2 Receives: Drug: Vγ2Vδ2 T lymphocyte-based immunotherapy; Drug: Treatment regimens for MDR-TB |
| Treatment regimens for MDR-TB | Active comparator | Treatment regimens was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis. Receives: Drug: Treatment regimens for MDR-TB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sputum smear and culture negative conversion
Sputum smear microscopy, bacterial culture. Bacterial culture was performed via a mycobacterial growth indicator tube (MGIT) using the BACTEC MGIT 960 system.
Measured: Through study completion, an average of 24 months.
Secondary outcomes (1)
Radiographic changes
Radiographic changes after treatment compared to baseline.Outcomes were defined as unchanged or deteriorated; ecovered; improved based on radiological findings compared to baseline.
Measured: Through study completion, an average of 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2022
- Study start3 Aug 2022
- Primary completion3 Aug 2025 (estimated)
- Study completion3 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MDR-TBStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Pulmonary Hospital, Shanghai, China
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Public Health Clinical Center, Huashan Hospital, No.85 Hospital, Changning, Shanghai, China
- Responsible party
- Principal investigator, Wei Sha MD & PhD, Shanghai Pulmonary Hospital, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05493267
- Sponsor's protocol ID
- L20-209
- Status last verified
- Aug 2022
- First submitted
- 3 Aug 2022
- Last updated
- 10 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Exploratory Study of Vγ2Vδ2 T Lymphocyte-based Immunotherapy for MDR-TB
- ClinicalTrials.gov ID
- NCT05493267
- Acronym / sponsor ID
- L20-209
- Conditions
- MDR-TB, Immunotherapy
- Keywords
- MDR-TB；Immunotherapy；
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Shanghai Pulmonary Hospital, Shanghai, ChinaUniversity, hospital or other
- Collaborators
- Shanghai Public Health Clinical Center, Huashan Hospital, No.85 Hospital, Changning, Shanghai, China
- Study start
- 3 Aug 2022 (actual)
- Primary completion
- 3 Aug 2025 (estimated)
- Study completion
- 3 Aug 2027 (estimated)
- First posted
- 9 Aug 2022 (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.
A Exploratory Study of drug combination (zoledronic acid/interleukin 2) that specifically amplifies Vγ2Vδ2 T cells in combination with anti-tuberculosis chemotherapy for the treatment of MDR-TB.
Detailed description
The emergence and prevalence of drug-resistant TB in recent years has made TB control more challenging, and MDR-TB is more serious type of drug-resistance TB with a cure rate of just over half, even with the latest treatment regimens. Treatment modalities other than drugs should be considered for patients with drug-resistant TB who have poor treatment efficacy, for patients with drug-resistant TB who are unresponsive to treatment, and for other patients for whom an effective treatment regimen cannot be composed.
The human immune system plays an important role in the infection, development, treatment and regression of tuberculosis.Mtb is an intracellularly parasitic bacterium that evades host immune clearance.Immunotherapy for TB can kill intracellularly parasitic Mycobacterium tuberculosis, including drug-resistant Mycobacterium tuberculosis, by inducing a host-specific immune response.The combination of antituberculosis chemotherapy and immunotherapy has the potential to open up new avenues for the treatment of multidrug-resistant TB.
In recent years, several studies by our team and others addressing host immune mechanisms have shown that γδ T cells play an important role in the fight against TB infection.Vγ2Vδ2 T cells (also known as Vγ9Vδ2 T cells) are a specific subset of γδ T cells, the only γδ T cells capable of recognizing TB phosphoantigens, and are found only in human and non-human primates.
Our previous study demonstrated that zoledronic acid, an anti-osteoporotic and osteoprotective drug, induced the production of endogenous ligands for Vγ2Vδ2T cells and activated Vγ2Vδ2T cells. Zoledronic acid in combination with interleukin 2 can significantly expand Vγ2Vδ2T cells, and the expanded Vγ2Vδ2T cells can effectively kill intracellular parasitic Mycobacterium tuberculosis, it can also promote the production of more anti-tuberculosis effectors by Vγ2Vδ2T cells and widely stimulate the production of functional cytokines by CD4 and CD8 T cells.
The primate experiments conducted by our team in the ABSL-III laboratory of Wuhan University demonstrated that phosphoantigen/interleukin 2 in a macaque model of tuberculosis infection induced lung phosphoantigen-specific Vγ2Vδ2 T cell expansion and migration, reduced Mycobacterium tuberculosis load in vivo, and effectively improved immune resistance to tuberculosis lung necrosis, demonstrating that targeted Vγ2Vδ2 T cell Immunotherapy of Vγ2Vδ2 T cells has a significant therapeutic effect on TB infection in monkeys , and is also safe for use in macaques. Accordingly, the investigators propose a drug combination (zoledronic acid/interleukin 2) that specifically amplifies Vγ2Vδ2 T cells in combination with anti-tuberculosis chemotherapy for the treatment of multidrug-resistant tuberculosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vγ2Vδ2 T lymphocyte-based immunotherapy +Treatment regimens for MDR-TB | Experimental | Drug: Vγ2Vδ2 T lymphocyte-based immunotherapy, Drug: Treatment regimens for MDR-TBTreatment was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis, with the addition of immunotherapy：zoledronic acid and recombinant human interleukin 2 |
| Treatment regimens for MDR-TB | Active comparator | Drug: Treatment regimens for MDR-TBTreatment regimens was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- RR-TB/MDR-TB (resistant to at least isoniazid and rifampicin).
- Poor efficacy of the original treatment regimen or no response to treatment or less than 4 effective drugs.
Key exclusion criteria (2 listed)
- Immunosuppression due to co-morbidities, such as immune system disorders, tumors, etc.
- Test confirms poor response to ZOL and IL-2 stimulation.
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 |
|---|---|---|
| Vγ2Vδ2 T lymphocyte-based immunotherapyAlso: Drug combination (zoledronic acid/interleukin 2)Intravenous injection of zoledronic acid, followed by a subcutaneous injection recombinant human interleukin. Zoledronic acid was administered 3 times and recombinant human interleukin was administered 10 times for a total of 6 months. | Drug | Vγ2Vδ2 T lymphocyte-based immunotherapy +Treatment regimens for MDR-TB |
| Treatment regimens for MDR-TBAlso: Treatment regimen for MDR-TB using WHO guidelinesTreatment regimens was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis. | Drug | Treatment regimens for MDR-TB, Vγ2Vδ2 T lymphocyte-based immunotherapy +Treatment regimens for MDR-TB |
Primary outcome
Sputum smear and culture negative conversion
Time frame: Through study completion, an average of 24 months.
Sputum smear microscopy, bacterial culture. Bacterial culture was performed via a mycobacterial growth indicator tube (MGIT) using the BACTEC MGIT 960 system.
1 secondary outcome
Radiographic changes
Time frame: Through study completion, an average of 24 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2022.
- 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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vγ2Vδ2 T lymphocyte-based immunotherapy and Treatment regimens for MDR-TB in people with MDR-TB and Immunotherapy, run by Shanghai Pulmonary Hospital, Shanghai, China at 2 sites 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 2 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 10 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sha Wei (+8602165115006 ext. 2017, 13671758200@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sputum smear and culture negative conversion (time frame: Through study completion, an average of 24 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 10 Aug 2022.