HIV-1 InfectionPhase 1NCT04620304
Study for Evaluation of the Safety, Pharmacokinetics, and Antiviral Activity of UB-421 Subcutaneous Formulation Administered in HIV-1 Infected Treatment Naive Patients
A Phase 1 study testing UB-421 SC(dB4C7C22-6 mAb) in people with HIV-1 Infection, run by United BioPharma at 1 site in Taiwan.
Trial summary
This is a phase I, open-label, dose-escalation study to investigate short-term safety, pharmacokinetics, and antiviral activity of UB-421 SC with 4 weekly doses in treatment naive HIV-1 infected patients. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- UB-421 SC(dB4C7C22-6 mAb)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Jan 2021to 25 May 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 seropositive, with documented HIV-1 infection by official, signed, written history (e.g. laboratory report);
- Male and female, age 20 years or older;
- Asymptomatic (generalized lymphadenopathy can be included), defined as subjects without stage 3 defining opportunistic illnesses according to revised Surveillance Case Definition for HIV Infection published in 2014, which was determined by the Investigator based on the medical history, physical examination, ECG, and laboratory evaluations;
- CD4+ (D1) T cell count > 350 cells/mm3 at the Screening Visit;
- HIV-1 viral load > 5,000 copies/mL at the Screening Visit;
- HIV antiretroviral therapy (ART)-naïve i.e., subjects who receive no prior or current HIV antiretroviral drugs;
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- Male subjects and female subjects of childbearing potential must agree to use the acceptable method of contraception during the course of the study (excluding women who are not of childbearing potential). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at the Screening Visit; Definitions Women NOT of childbearing potential: women who are permanently or surgically sterilized or postmenopausal. Permanent sterilization includes hysterectomy, and/or bilateral oophorectomy, and/or bilateral salpingectomy and/or tubal ligation.
- Postmenopausal women: 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.
- Acceptable method of birth control for WOCBP: abstinence; implant; intrauterine device; hormonal contraceptive (injectable, oral contraceptives, transdermal patches, or contraceptive rings) plus barrier method (male condom, female condom or diaphragm).
- Acceptable method of birth control for male subjects: abstinence; condom.
- Subjects signed the informed consent before undergoing any study procedures. -
Who cannot join
- Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study;
- Subjects with acute opportunistic infection(s) or bacterial infection(s), that the delayed initiation of ART would not be allowed, as judged by the Investigator;
- Any stage 3 defining opportunistic illnesses such as Kaposi's sarcoma according to the revised Surveillance Case Definition for HIV Infection published in 2014 within the past 12 months before the Screening Visit;
- Serious illness requiring systemic treatment and/or hospitalization for at least 7 days prior to the Screening Visit;
- Any previous exposure to a monoclonal antibody within 12 weeks prior to the Screening Visit;
- Any previous hypersensitivity reaction to monoclonal antibody;
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- Any significant diseases (other than HIV-1 infection) or clinically significant findings that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy;
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);
- Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test within 12 weeks prior to the Screening Visit;
- Serum GPT/ALT value is 3 times or greater than the upper limit of normal (≥ 3 xULN) at the Screening Visit;
- Serum GOT/AST value is 3 times or greater than the upper limit of normal (≥ 3 xULN) at the Screening Visit;
- Serum total bilirubin (TBIL) value is 1.5 times or greater than the upper limit of normal (≥1.5 xULN) at the Screening Visit;
- Serum creatinine value is greater than 1.3 times the upper limit of normal (>1.3xULN) at the Screening Visit;
- Any vaccination within 8 weeks prior to the Screening Visit;
- Any treatment with immunomodulators, such as interleukins, interferon, cyclosporine, systemic corticosteroid, or systemic chemotherapy within 12 weeks prior to the Screening Visit; Note: Subjects received short-term low dose oral (i.e. prednisone ≤0.5mg/kg/day for ≤ 1-month duration), inhaled, nasal, or topical steroids will not be excluded.
- Prior participation in any HIV vaccine trial;
- Subjects who have ever received UB-421 IV or SC formulations;
- Receipt of other investigational study agent within 12 weeks before the Screening Visit;
- Life expectancy of less than 12 months;
- Any current alcohol or illicit drug use that, in the Investigator's opinion, would interfere with the subject's ability to comply with the dosing and visit schedules and protocol evaluations.
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open-Label, Multi-Dose Study for Evaluation of the Safety, Pharmacokinetics, and Antiviral Activity of UB-421 Subcutaneous Formulation Administered in HIV-1 Infected Treatment Naive Patients
This is a phase I, open-label, dose-escalation study to investigate short-term safety, pharmacokinetics, and antiviral activity of UB-421 SC with 4 weekly doses in treatment naive HIV-1 infected patients. Eligible (n=6 per dose cohort) subjects will be sequentially enrolled into 3 escalating-dose cohorts to receive 4 weekly fixed doses of UB-421 SC at either 250 mg (Cohort A), 500 mg (Cohort B) or 700 mg (Cohort C). Subjects should be followed for safety for additional 4 weeks after the last UB-421 SC dosing. In order to control viral load while minimizing confounding in safety assessment, subjects can initiate standard anti-retroviral therapy (ART) two weeks after the last UB-421 SC dosing.
Escalation to the next higher dose cohort will be determined based on dose limited toxicity (DLT) evaluation. The dose escalation will be stopped if ≥ 2/6 subjects experience DLT or when clinical trial steering committee (CTSC) determines it is not suitable to escalate the dose level.
Read more
In this study, DLT is defined as any ≥ grade 3 AE occurred within 21 days from prior UB-421 SC dosing and is considered drug related.
When there is any ≥grade 3 AE(s) occurred within 21 days from prior UB-421 SC dosing in any subject out of the current dose cohort (n=6), the duty of the CTSC will be initiated. The CTSC will be responsible for DLT evaluation. The committee members will evaluate the safety data of all subjects in each cohort through baseline to at least 21 days following the last UB-421 SC dosing. The administration of the next higher dose level at TV1 will be conducted after the committee grants the dose escalation. However, dose escalation will be proceeded if there is no ≥ grade 3 AE and upon agreement from all investigators without holding the steering committee meeting.
Subjects will be assessed at Screening, weekly during Treatment Period and Follow-up Period. The assessment includes physical examination, vital sign, laboratory parameters, HIV-1 viral load, CD4+ and CD8+ T-cell counts. Samples for the drug concentration measurement will be collected at weekly intervals throughout the study, immediately before UB-421 SC dosing. Additional intensive PK sampling will be scheduled during the first dosing interval (from TV1 to TV2) at 1, 3, 6, 24, 48, 72 and 96 hours post first UB-421 SC dosing for PK subgroup (at least 3 subjects per dose cohort). The immunogenicity of UB-421 SC will be monitored by measuring anti-UB-421 antibodies in pre-dose serum samples at day 0 and post-dose serum at day 14, 28, 35, 42 and 49. Viral reservoir, immunophenotyping and CD4+ (D1) receptor occupancy will also be explored.
Subjects should discontinue from UB-421 SC treatment if they experience a sustained decrease from baseline in CD4+ (D2) T cell counts of ≧50% at two consecutive visits or drug-related AE(s) with severity grade 3 or 4 (according to the Division of AIDS, National Institute of Allergy and Infectious Diseases (DAIDS) AE grading).
- Conditions
- HIV-1 Infection
- Being tested
- UB-421 SC(dB4C7C22-6 mAb)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UB-421 SC(dB4C7C22-6 mAb)Biological
The UB-421 SC (dB4C7C22-6 mAb) will be supplied at a concentration of 125 mg/mL after reconstitution. Subjects will receive weekly UB-421 SC injections during the 4-week Treatment Period.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | receive 4 weekly fixed doses of UB-421 SC at 250 mg Receives: Biological: UB-421 SC(dB4C7C22-6 mAb) |
| Cohort B | Experimental | receive 4 weekly fixed doses of UB-421 SC at 500 mg Receives: Biological: UB-421 SC(dB4C7C22-6 mAb) |
| Cohort C | Experimental | receive 4 weekly fixed doses of UB-421 SC at 700 mg Receives: Biological: UB-421 SC(dB4C7C22-6 mAb) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Numbers and incidence of TEAEs
Numbers and incidence of TEAEs that are ≥ Grade 2 and study treatment related, TEAEs (any grades) by maximum severity, TEAEs by relationship to study treatment, SAEs, TEAEs leading to death, and TEAEs leading to discontinuation of study treatment will be tabulated by dose cohort and will be summarized by system organ class and preferred term for study period (Treatment or Follow-up). The "Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events" will be used in this study for all AE severity grading, except skin abnormalities, which will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE).
Measured: 28 days
Secondary outcomes (5)
The virologic responses during the Treatment Period
The proportion of subjects ever achieving HIV-1 RNA reduction > X log10 copies/mL;
Measured: 28 days
Pharmacokinetics (PK) of UB-421 SC
- Ctrough for each dosing interval
Measured: 28 days
Pharmacokinetics (PK) of UB-421 SC
Cmax of first dosing interval;
Measured: 28 days
Pharmacokinetics (PK) of UB-421 SC
AUC0-inf (if applicable).
Measured: 28 days
The virologic responses during the Treatment Period (from TV1 to EOT)
The proportion of subjects with virologic rebound
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2020
- Study start1 Jan 2021
- Primary completion25 May 2022
- Study completion25 May 2022
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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- United BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Veterans General Hospital., Taoyuan General Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04620304
- Sponsor's protocol ID
- UBP-A122-HIV
- Status last verified
- Apr 2023
- First submitted
- 22 Oct 2020
- Last updated
- 24 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Multi-Dose Study for Evaluation of the Safety, Pharmacokinetics, and Antiviral Activity of UB-421 Subcutaneous Formulation Administered in HIV-1 Infected Treatment Naive Patients
- ClinicalTrials.gov ID
- NCT04620304
- Acronym / sponsor ID
- UBP-A122-HIV
- Conditions
- HIV-1 Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- United BioPharmaIndustry (pharma, biotech, devices)
- Collaborators
- Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Veterans General Hospital., Taoyuan General Hospital
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 25 May 2022 (actual)
- Study completion
- 25 May 2022 (actual)
- First posted
- 6 Nov 2020 (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 phase I, open-label, dose-escalation study to investigate short-term safety, pharmacokinetics, and antiviral activity of UB-421 SC with 4 weekly doses in treatment naive HIV-1 infected patients. Eligible (n=6 per dose cohort) subjects will be sequentially enrolled into 3 escalating-dose cohorts to receive 4 weekly fixed doses of UB-421 SC at either 250 mg (Cohort A), 500 mg (Cohort B) or 700 mg (Cohort C). Subjects should be followed for safety for additional 4 weeks after the last UB-421 SC dosing. In order to control viral load while minimizing confounding in safety assessment, subjects can initiate standard anti-retroviral therapy (ART) two weeks after the last UB-421 SC dosing.
Escalation to the next higher dose cohort will be determined based on dose limited toxicity (DLT) evaluation. The dose escalation will be stopped if ≥ 2/6 subjects experience DLT or when clinical trial steering committee (CTSC) determines it is not suitable to escalate the dose level.
In this study, DLT is defined as any ≥ grade 3 AE occurred within 21 days from prior UB-421 SC dosing and is considered drug related.
When there is any ≥grade 3 AE(s) occurred within 21 days from prior UB-421 SC dosing in any subject out of the current dose cohort (n=6), the duty of the CTSC will be initiated. The CTSC will be responsible for DLT evaluation. The committee members will evaluate the safety data of all subjects in each cohort through baseline to at least 21 days following the last UB-421 SC dosing. The administration of the next higher dose level at TV1 will be conducted after the committee grants the dose escalation. However, dose escalation will be proceeded if there is no ≥ grade 3 AE and upon agreement from all investigators without holding the steering committee meeting.
Subjects will be assessed at Screening, weekly during Treatment Period and Follow-up Period. The assessment includes physical examination, vital sign, laboratory parameters, HIV-1 viral load, CD4+ and CD8+ T-cell counts. Samples for the drug concentration measurement will be collected at weekly intervals throughout the study, immediately before UB-421 SC dosing. Additional intensive PK sampling will be scheduled during the first dosing interval (from TV1 to TV2) at 1, 3, 6, 24, 48, 72 and 96 hours post first UB-421 SC dosing for PK subgroup (at least 3 subjects per dose cohort). The immunogenicity of UB-421 SC will be monitored by measuring anti-UB-421 antibodies in pre-dose serum samples at day 0 and post-dose serum at day 14, 28, 35, 42 and 49. Viral reservoir, immunophenotyping and CD4+ (D1) receptor occupancy will also be explored.
Subjects should discontinue from UB-421 SC treatment if they experience a sustained decrease from baseline in CD4+ (D2) T cell counts of ≧50% at two consecutive visits or drug-related AE(s) with severity grade 3 or 4 (according to the Division of AIDS, National Institute of Allergy and Infectious Diseases (DAIDS) AE grading).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Biological: UB-421 SC(dB4C7C22-6 mAb)receive 4 weekly fixed doses of UB-421 SC at 250 mg |
| Cohort B | Experimental | Biological: UB-421 SC(dB4C7C22-6 mAb)receive 4 weekly fixed doses of UB-421 SC at 500 mg |
| Cohort C | Experimental | Biological: UB-421 SC(dB4C7C22-6 mAb)receive 4 weekly fixed doses of UB-421 SC at 700 mg |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- HIV-1 seropositive, with documented HIV-1 infection by official, signed, written history (e.g. laboratory report);
- Male and female, age 20 years or older;
- Asymptomatic (generalized lymphadenopathy can be included), defined as subjects without stage 3 defining opportunistic illnesses according to revised Surveillance Case Definition for HIV Infection published in 2014, which was determined by the Investigator based on the medical history, physical examination, ECG, and laboratory evaluations;
- CD4+ (D1) T cell count > 350 cells/mm3 at the Screening Visit;
- HIV-1 viral load > 5,000 copies/mL at the Screening Visit;
Key exclusion criteria (21 listed)
- Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study;
- Subjects with acute opportunistic infection(s) or bacterial infection(s), that the delayed initiation of ART would not be allowed, as judged by the Investigator;
- Any stage 3 defining opportunistic illnesses such as Kaposi's sarcoma according to the revised Surveillance Case Definition for HIV Infection published in 2014 within the past 12 months before the Screening Visit;
- Serious illness requiring systemic treatment and/or hospitalization for at least 7 days prior to the Screening Visit;
- Any previous exposure to a monoclonal antibody within 12 weeks prior to the Screening Visit;
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 |
|---|---|---|
| UB-421 SC(dB4C7C22-6 mAb)The UB-421 SC (dB4C7C22-6 mAb) will be supplied at a concentration of 125 mg/mL after reconstitution. Subjects will receive weekly UB-421 SC injections during the 4-week Treatment Period. | Biological | Cohort A, Cohort B, Cohort C |
Primary outcome
Numbers and incidence of TEAEs
Time frame: 28 days
Numbers and incidence of TEAEs that are ≥ Grade 2 and study treatment related, TEAEs (any grades) by maximum severity, TEAEs by relationship to study treatment, SAEs, TEAEs leading to death, and TEAEs leading to discontinuation of study treatment will be tabulated by dose cohort and will be summarized by system organ class and preferred term for study period (Treatment or Follow-up). The "Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events" will be used in this study for all AE severity grading, except skin abnormalities, which will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE).
5 secondary outcomes
The virologic responses during the Treatment Period
Time frame: 28 days
Pharmacokinetics (PK) of UB-421 SC
Time frame: 28 days
Pharmacokinetics (PK) of UB-421 SC
Time frame: 28 days
Pharmacokinetics (PK) of UB-421 SC
Time frame: 28 days
The virologic responses during the Treatment Period (from TV1 to EOT)
Time frame: 28 days
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 24 Apr 2023.
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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.
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 UB-421 SC(dB4C7C22-6 mAb) in people with HIV-1 Infection, run by United BioPharma at 1 site in Taiwan.
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 11 inclusion and 21 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 24 Apr 2023. 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 Taiwan. 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?
Numbers and incidence of TEAEs (time frame: 28 days). 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 24 Apr 2023.