Study for Evaluation of the Safety, Pharmacokinetics, and Antiviral Activity of UB-421 Subcutaneous Formulation in HIV Infected Adults

NCT04620291 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: UBP-A127-HIV
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

UB-421 subcutaneous formulation (UB-421 SC) is developed to provide HIV infected patients a more convenient drug delivery method. UB-421 SC injection, with significantly less injection time than IV infusions and with opportunity of self-administration or administered in general medical setting (in addition to HIV-specific clinic), can provide patient a more convenient option. This UB-421 SC phase I study will be conducted to investigate short-term safety, pharmacokinetics and anti-viral activity of UB-421 SC at three dose levels in ART-treated aviremic subjects and treatment naive HIV-infected subjects. The current UB-421 SC formulation (125 mg/ml) is at least 10-fold more concentrated than UB-421 IV (10 mg/ml). The highly concentrated formulation makes weekly UB-421 subcutaneous injections feasible. This study will form the basis of UB-421 SC in combination with antiretroviral agents (ARV) for treating HIV infected viremic patients in the future clinical trials.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• 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).

  28 days

Secondary Outcomes (4)

• The virologic responses during the Treatment Period

  28 days

• PK of UB-421 SC

  28 days

• PK of UB-421 SC

  28 days

• PK of UB-421 SC

  28 days

Other Outcomes (1)

• Serum anti UB-421 antibody level

  49 days

Study Arms (5)

Cohort A

EXPERIMENTAL

250 mg UB-421 SC: ART-treated subjects

Biological: UB-421 SC

Cohort B

EXPERIMENTAL

500 mg UB-421 SC: ART-treated subjects

Biological: UB-421 SC

Cohort C

EXPERIMENTAL

700 mg UB-421 SC: ART-treated subjects

Biological: UB-421 SC

Cohort D

EXPERIMENTAL

500 mg UB-421 SC: Treatment naive subjects

Biological: UB-421 SC

Cohort E

EXPERIMENTAL

700 mg UB-421 SC: Treatment naive subjects

Biological: UB-421 SC

Interventions

UB-421 SC 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.

Also known as: Humanized dB4C7C22-6 monoclonal antibody

Cohort A; Cohort B; Cohort C; Cohort D; Cohort E

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The blips are \<400 copies/mL, and
• Part B:
• D. HIV-1 viral load \>200 copies/mL at the SV; E. HIV antiretroviral therapy (ART)-naïve i.e., subjects who receive no prior or current ART.
• However, subjects who have previously received pre- or post-exposure prophylaxis but eventually confirmed HIV-1 seropositive can be enrolled; F. 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;
• HIV-1 seropositive, with documented HIV-1 infection by official, signed, written history (e.g.
• laboratory report);
• Male and female, age 18 years or older;
• CD4+ (D1) T cell count \> 350 cells/mm3 at the SV;
• 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 SV; 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.

You may not qualify if:

• Subjects who have any of the following conditions will be excluded from both Part A and B
• 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 SV;
• Serious illness requiring systemic treatment and/or hospitalization for at least 7 days prior to the SV;
• Any previous exposure to a monoclonal antibody within 12 weeks prior to the SV;
• Any previous hypersensitivity reaction to monoclonal antibody;
• Have ever experienced urticaria in the previous 2 years before the SV or with ongoing dermatologic problem with rash appearance (eg. eczema, atopic dermatitis, urticaria) at the SV;
• 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 HCV antibody and RNA double positive at the Screening Visit or within 12 weeks prior to the SV;
• Serum GPT/ALT value is 2.5 times or greater than the upper limit of normal (≥ 2.5 xULN) at the Screening Visit;
• Serum GOT/AST value is 2.5 times or greater than the upper limit of normal (≥ 2.5 xULN) at the Screening Visit;
• Serum total bilirubin (TBIL) value is 2.5 times or greater than the upper limit of normal (≥ 2.5 xULN) at the SV;
• Serum creatinine value is greater than 1.5 times the upper limit of normal (\> 1.5 x ULN) at the SV;

Sponsors & Collaborators

• United BioPharma: lead

Central Study Contacts

Linda Shih, Master

CONTACT

+886-3-668-4800; linda.shih@unitedbiopharma.com

Zhonghao Shi

CONTACT

+886-3-668-4800; zhonghao.shi@unitedbiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2020
• First Posted: November 6, 2020
• Study Start: December 31, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 13, 2022

Record last verified: 2022-05