HIV-1-infectionPhase 1NCT04027387
Dose Escalation Safety Study of TMB-365 in HIV-1 Infected Participants
A Phase 1 study testing TMB-365 in people with HIV-1-infection, run by TaiMed Biologics Inc. at 6 sites in 2 countries.
Trial summary
This study will evaluate the safety and behavior in the body of the experimental drug TMB-365 in people with HIV-1 infection. This will be the first test of TMB-365 in humans. One dose of the study drug is given to each participant, followed by 10 weeks of monitoring for safety and levels of the drug in the blood. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- TMB-365
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 14 Dec 2019to 18 Aug 2021
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female at least 18 years of age and no greater than 60 years on the day of Screening
- Asymptomatic HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by Geenius™ or a second antibody test by a method other than the initial rapid HIV and/or E/CIA test, or by HIV-1 antigen, plasma HIV-1 RNA viral load
- Has not received ART for three months prior to the first dose.
- Screening HIV-1 RNA ≥ 1,000 copies/mL and < 100,000 copies/mL obtained within 60 days prior to the first dose.
- Laboratory values obtained within 60 days prior to the first dose:
- Hemoglobin > 10.0 g/dL
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- Platelet count ≥ 100,000/mm3
- Absolute neutrophil count ≥ 1,000/mm3
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 x upper limit of normal (ULN)
- Creatinine clearance (CrCl) of ≥ 50 mL/min
- Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
- In the opinion of the principal investigator or designee, has understood the information provided; written informed consent needs to be given before any study-related procedures are performed
- Females of childbearing potential, sexually active with a male sex partner, must agree to use one effective method of contraception from the time of signing the consent to completion of the study, and agree to pregnancy testing as per the Schedule of Events and Procedures. Females of childbearing potential are female participants who are not surgically sterile (no history of bilateral tubal ligation, hysterectomy, or bilateral salpingo-oophorectomy), are not postmenopausal (at least one year without menses), and are not otherwise sterile by medical evaluation.
Who cannot join
- Receipt of TMB-365, TROGARZO (ibalizumab-uiyk), or any anti-CD4 therapeutic (e.g., UB-421) at any time prior to the first dose
- Pregnant, planning a pregnancy during the trial period, or lactating.
- Known allergy/sensitivity or any hypersensitivity to components of the study drug or its formulation, or known allergy to a MAb
- Major psychiatric illness including any history of schizophrenia or severe psychosis, bipolar disorder requiring therapy, or suicide attempt in the previous three years
- Serious illness requiring systemic treatment and/or hospitalization within 21 days prior to the first dose
- Receipt of immunomodulatory agents (e.g., interleukins, interferons, cyclosporine, high dose systemic corticosteroids), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 180 days prior to the first dose
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- Any chronic or acute medical condition, including drug use and alcohol abuse, which in the opinion of the investigator would interfere with evaluation of the study drug
- Lack of adequate venous access
- Individuals who have experienced virologic failure during treatment with two or more cART treatment regimens. Note that a change in treatment regimen for intolerance is not considered treatment failure.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
North Texas Infectious Disease Consultants
Dallas, Texas, 75246
Midway Immunology and Research Center
Ft. Pierce, Florida, 34982
University of Mississippi Medical Center Division of Infectious Diseases
Jackson, Mississippi, 39213
Orlando Immunology Center
Orlando, Florida, 32803
Quest Clinical Research
San Francisco, California, 94115
About this study
Official title: A Phase Placebo-Controlled, Sequential Single Dose Escalation Study of the Safety, Pharmacokinetics, and Antiretroviral Activity of IVTMB-365 in HIV-1 Infected Participants
This study will evaluate the safety and behavior in the body of the experimental drug TMB-365 in people with HIV-1 infection. This will be the first test of TMB-365 in humans. One dose of the study drug is given to each participant, followed by 10 weeks of monitoring for safety and levels of the drug in the blood. The first group of participants will receive the lowest dose (400 mg). If no safety concerns are seen, the next group will begin at a higher dose (800 mg). If no safety concerns are seen in the second group, the third group will begin at the highest dose in this study (1600 mg).
Read the detailed description
This phase 1, randomized, double-blinded, placebo-controlled, sequential single dose escalation study will evaluate the safety, tolerability and pharmacokinetic (PK) parameters of TMB-365 administered via intravenous infusion (IV) to HIV-1 infected participants at one of three successively increasing dose levels: 400 mg, 800 mg, and 1600 mg. Each participant will be monitored for 10 weeks post-administration. All participants will be expected to participate in PK sampling during Weeks 1, 4, 5, and 6.
Beginning with the lowest dosage group, a Data Monitoring Committee (DMC) will review available data after four participants have completed two weeks of post-dose follow-up to determine if dosing of the next dosage group may proceed.
If no dose limiting toxicities (DLTs) emerge, defined as a single Grade 4 or two of the same Grade 3 clinical or laboratory adverse events deemed possibly, probably or definitely related to the study drug, or a serious adverse event deemed possibly, probably or definitely related to the study drug as graded by the DAIDS Table for Grading Severity of Adult and Pediatric Adverse Events Version 2.1, then dosing of the next higher dose group will be permitted.
Dosing in the highest dose group will begin after four of the eight participants in second group have successfully completed the scheduled study drug administration and two weeks of follow-up, and those data, along with all available data from the initial dose group have been reviewed by the DMC and no DLTs or SAEs as defined above are identified.
All participants may initiate standard combination antiretroviral therapy six weeks after receiving the study drug.
- Conditions
- HIV-1-infection
- Being tested
- TMB-365
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMB-365Biological
An IgG1 monoclonal antibody targeting domain 2 of the CD4 receptor for treatment of HIV-1 infection
| Study group | Role | What they receive |
|---|---|---|
| TMB-365 400 mg- Group 1 | Experimental | Single dose of TMB-365 400 mg or matching placebo by intravenous infusion Receives: Biological: TMB-365 |
| TMB-365 800 mg- Group 2 | Experimental | Single dose of TMB-365 800 mg or matching placebo by intravenous infusion Receives: Biological: TMB-365 |
| TMB-365 1600 mg- Group 3 | Experimental | Single dose of TMB-365 1600 mg or matching placebo by intravenous infusion Receives: Biological: TMB-365 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of a single 400mg dose of TMB-365
% of subjects with treatment-emergent adverse events
Measured: 10 weeks
Safety of a single 800mg dose of TMB-365
% of subjects with treatment-emergent adverse events
Measured: 10 weeks
Safety of a single 1600mg dose of TMB-365
% of subjects with treatment-emergent adverse events
Measured: 10 weeks
Pharmacokinetics of a single 400mg dose of TMB-365
% CD4 receptor occupancy
Measured: 4 weeks
Pharmacokinetics of a single 800mg dose of TMB-365
% CD4 receptor occupancy
Measured: 4 weeks
Pharmacokinetics of a single 1600mg dose of TMB-365
% CD4 receptor occupancy
Measured: 4 weeks
Secondary outcomes (3)
Antiviral activity of a single 400 mg dose of TMB-365
Change in log10 plasma HIV-1 RNA
Measured: 2 weeks
Antiviral activity of a single 800 mg dose of TMB-365
Change in log10 plasma HIV-1 RNA
Measured: 2 weeks
Antiviral activity of a single 1600 mg dose of TMB-365
Change in log10 plasma HIV-1 RNA
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2019
- Study start14 Dec 2019
- Primary completion18 Aug 2021
- Study completion18 Aug 2021
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.
- 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
- Randomised
- Intervention model
- Sequential
- Model description
- Single dose escalation
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- TaiMed Biologics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Westat
- Responsible party
- Sponsor
- Investigators
- Steve Weinheimer, PhD, Study director, TaiMed Biologics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04027387
- Sponsor's protocol ID
- TMB-365-101
- Status last verified
- Oct 2021
- First submitted
- 17 Jul 2019
- Last updated
- 6 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Placebo-Controlled, Sequential Single Dose Escalation Study of the Safety, Pharmacokinetics, and Antiretroviral Activity of IVTMB-365 in HIV-1 Infected Participants
- ClinicalTrials.gov ID
- NCT04027387
- Acronym / sponsor ID
- TMB-365-101
- Conditions
- HIV-1-infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- TaiMed Biologics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Westat
- Study start
- 14 Dec 2019 (actual)
- Primary completion
- 18 Aug 2021 (actual)
- Study completion
- 18 Aug 2021 (actual)
- First posted
- 22 Jul 2019 (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 study will evaluate the safety and behavior in the body of the experimental drug TMB-365 in people with HIV-1 infection. This will be the first test of TMB-365 in humans. One dose of the study drug is given to each participant, followed by 10 weeks of monitoring for safety and levels of the drug in the blood. The first group of participants will receive the lowest dose (400 mg). If no safety concerns are seen, the next group will begin at a higher dose (800 mg). If no safety concerns are seen in the second group, the third group will begin at the highest dose in this study (1600 mg).
Detailed description
This phase 1, randomized, double-blinded, placebo-controlled, sequential single dose escalation study will evaluate the safety, tolerability and pharmacokinetic (PK) parameters of TMB-365 administered via intravenous infusion (IV) to HIV-1 infected participants at one of three successively increasing dose levels: 400 mg, 800 mg, and 1600 mg. Each participant will be monitored for 10 weeks post-administration. All participants will be expected to participate in PK sampling during Weeks 1, 4, 5, and 6.
Beginning with the lowest dosage group, a Data Monitoring Committee (DMC) will review available data after four participants have completed two weeks of post-dose follow-up to determine if dosing of the next dosage group may proceed.
If no dose limiting toxicities (DLTs) emerge, defined as a single Grade 4 or two of the same Grade 3 clinical or laboratory adverse events deemed possibly, probably or definitely related to the study drug, or a serious adverse event deemed possibly, probably or definitely related to the study drug as graded by the DAIDS Table for Grading Severity of Adult and Pediatric Adverse Events Version 2.1, then dosing of the next higher dose group will be permitted.
Dosing in the highest dose group will begin after four of the eight participants in second group have successfully completed the scheduled study drug administration and two weeks of follow-up, and those data, along with all available data from the initial dose group have been reviewed by the DMC and no DLTs or SAEs as defined above are identified.
All participants may initiate standard combination antiretroviral therapy six weeks after receiving the study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Single dose escalation
| Arm | Type | Receives |
|---|---|---|
| TMB-365 400 mg- Group 1 | Experimental | Biological: TMB-365Single dose of TMB-365 400 mg or matching placebo by intravenous infusion |
| TMB-365 800 mg- Group 2 | Experimental | Biological: TMB-365Single dose of TMB-365 800 mg or matching placebo by intravenous infusion |
| TMB-365 1600 mg- Group 3 | Experimental | Biological: TMB-365Single dose of TMB-365 1600 mg or matching placebo by intravenous infusion |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Male or female at least 18 years of age and no greater than 60 years on the day of Screening
- Asymptomatic HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by Geenius™ or a second antibody test by a method other than the initial rapid HIV and/or E/CIA test, or by HIV-1 antigen, plasma HIV-1 RNA viral load
- Has not received ART for three months prior to the first dose.
- Screening HIV-1 RNA ≥ 1,000 copies/mL and < 100,000 copies/mL obtained within 60 days prior to the first dose.
- Laboratory values obtained within 60 days prior to the first dose:
Key exclusion criteria (9 listed)
- Receipt of TMB-365, TROGARZO (ibalizumab-uiyk), or any anti-CD4 therapeutic (e.g., UB-421) at any time prior to the first dose
- Pregnant, planning a pregnancy during the trial period, or lactating.
- Known allergy/sensitivity or any hypersensitivity to components of the study drug or its formulation, or known allergy to a MAb
- Major psychiatric illness including any history of schizophrenia or severe psychosis, bipolar disorder requiring therapy, or suicide attempt in the previous three years
- Serious illness requiring systemic treatment and/or hospitalization within 21 days prior to the first dose
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 |
|---|---|---|
| TMB-365An IgG1 monoclonal antibody targeting domain 2 of the CD4 receptor for treatment of HIV-1 infection | Biological | TMB-365 1600 mg- Group 3, TMB-365 400 mg- Group 1, TMB-365 800 mg- Group 2 |
Primary outcome
Safety of a single 400mg dose of TMB-365
Time frame: 10 weeks
% of subjects with treatment-emergent adverse events
Safety of a single 800mg dose of TMB-365
Time frame: 10 weeks
% of subjects with treatment-emergent adverse events
Safety of a single 1600mg dose of TMB-365
Time frame: 10 weeks
% of subjects with treatment-emergent adverse events
Pharmacokinetics of a single 400mg dose of TMB-365
Time frame: 4 weeks
% CD4 receptor occupancy
Pharmacokinetics of a single 800mg dose of TMB-365
Time frame: 4 weeks
% CD4 receptor occupancy
Pharmacokinetics of a single 1600mg dose of TMB-365
Time frame: 4 weeks
% CD4 receptor occupancy
3 secondary outcomes
Antiviral activity of a single 400 mg dose of TMB-365
Time frame: 2 weeks
Antiviral activity of a single 800 mg dose of TMB-365
Time frame: 2 weeks
Antiviral activity of a single 1600 mg dose of TMB-365
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2021.
- 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.
Steve Weinheimer, PhD study director
TaiMed Biologics
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TMB-365 in people with HIV-1-infection, run by TaiMed Biologics Inc. at 6 sites in 2 countries.
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 13 inclusion and 9 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: finished, as of the sponsor's last update on 6 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Puerto Rico. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety of a single 400mg dose of TMB-365 (time frame: 10 weeks). The study lists 6 primary outcomes in all. 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 6 Oct 2021.