Clinical Trials

MainTitle

A Phase 1, Single Dose Study of the Safety and Virologic Effect of an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS) or VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously to HIV-Infected Adults

Purpose

Purpose

Background:

The human body uses antibodies as one way to help fight infection. VRC01LS and VRC07-523LS are antibodies directed against the HIV virus. Researchers want to see if they are safe and well tolerated. In Part A of the study, the researchers studied VRC01LS. Enrollment in Part A of the study is finished. In Part B, the researchers are studying VRC07-523LS. Depending on which antibody received, they will study the amount of VRC01LS or VRC07-523LS in the body and how it changes over time. They will check to see if people who get VRC01LS or VRC07-523LS develop an immune response to it.

Objective:

To see if VRC01LS and VRC07-523LS are safe and well tolerated.

Eligibility:

Adults ages 18-70 who are HIV infected but otherwise healthy. Females who are able to get pregnant must be willing to use birth control during the study.

Design:

Participants will get the study drug one time, by IV infusion. A needle will guide a thin tube into a vein. The study drug mixed with salt water will be dripped into the vein over about 30 minutes.

Participants will be monitored for 30 minutes after the infusion.

Blood samples will be taken at the following times:

• Once before the infusion
• 5 times in the 4 hours after the infusion
• 1 time 24 hours after infusion. Some participants may have 3 optional blood draws in the

time period between 4 and 24 hours.

For 3 days after the infusion, participants will write their temperature and symptoms in a diary.

There will be a total of 23 study visits over 48 weeks. Ten visits will be in the first 4 weeks. At all visits, participants will answer health questions and give blood samples.

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures

• Evaluate the safety and tolerability [ Time Frame: Through 48 weeks post study product administration ]
  To evaluate the safety and tolerability of VRC0lLS or VRC07-523LS administered at 40 mg/kg to HIV-infected viremic adults.

Secondary Outcome Measures:

• Evaluate the pharmacokinetics [ Time Frame: Through 48 weeks post study product administration. ]
  To evaluate the pharmacokinetics of VRC0lLS or VRC07-523LS at 40 mg/kg IV.
• Evaluate CD4 count and viral load [ Time Frame: Through 48 weeks post study product administration. ]
  To evaluate the effects on CD4 count and viral load.
• Presence anti drug antibody [ Time Frame: Post administration. ]
  To determine the presence of anti-drug antibody.

Detailed Description:

Study Design:
Open-label, single dose study to examine safety, tolerability, pharmacokinetics and virologic impact of VRC01LS or VRC07-523LS in HIV-infected viremic adults.
Study Hypotheses:
This is the first study of VRC01LS or VRC07-523LS in HIV-infected viremic adults. The primary hypothesis is that both VRC01LS and VRC07-523LS will be safe for intravenous administration to HIV-1-infected adults. The secondary hypothesis is that VRC01LS and VRC07-523LS will be detectable in human sera with a definable halflife. Part A (VRC01LS) of the study has completed enrollment.
Product Description:
VRC-HIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB075-00-AB are human MAbs targeted to the CD4+ binding site of HIV-1. Both MAbs are modifications of the VRC01 MAb (which has been shown to be safe and to have antiviral activity in human studies) with the addition of the LS , a 2-amino acid mutation designed to improve the half-life of the antibody. There are no changes to the Fab binding sites. These MAbs were developed and manufactured by VRC/NIAID/NIH under cGMP at the VRC Vaccine Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD. Vials are provided at 100 mg/mL.
Participants:
HIV-1-infected viremic adults; 18-70 years of age.
Study Plan:
This study will assess VRC01LS or VRC07-523LS administered at 40 mg/kg IV in HIV-infected viremic participants. Participants will enroll in one of two parts: Part A (VRC01LS) and Part B (VRC07-523LS). Enrollment into Part A (VRC01LS) is complete. Part B enrollment will include 7 participants (up to 10 participants may be enrolled in the event that there are participants who do not complete the sampling schedule) who will receive VRC07-523LS. Safety lab samples, HIV viral load, CD4+ count, PK samples, and blood samples for human anti-VRC01LS antibody (Part A) and human anti-VRC07-523LS antibody (Part B) detection will be drawn at baseline and intervals throughout the study. Participants will keep a daily diary of reactogenicity symptoms for 3 days after study product administration and will be queried at each study visit for adverse events. Participants in Part B will be strongly encouraged to initiate 3-drug ART (prescribed by their primary HIV clinician; not study-provided) any time after completing day 14 study evaluations. Results from Part A and Part B may be analyzed, published, and presented separately since they involve two different MAbs.
VRC 607/A5378 Study Schema:

• Part: A (Enrollment Complete); Participants: 7; Product: VRC01LS; Administration Schedule (Day 0): 40 mg/kg IV.
• Part: B; Participants: 7; Product: VRC07-523LS; Administration Schedule (Day 0): 40 mg/kg IV.
  • Total Participants: 14*
    • The expected enrollment is 14 participants (i.e., a minimum of 7 participants in each part). However, up to 20 participants (i.e., 10 participants in each part) may be enrolled in the event that there are participants who do not complete the sampling schedule, if additional PK evaluations are needed, or if additional participants are needed for safety evaluations.
    
    Study Duration:
  
  Participants will be followed for 48 weeks after study product administration.
  Eligibility

  Eligibility

  Ages Eligible for Study:	18 Years to 70 Years
  Sexes Eligible for Study:	All
  Accepts Healthy Volunteers:	No

  Criteria

  • INCLUSION CRITERIA:
  
  A participant must meet all of the following criteria:
  1. Able and willing to complete the informed consent process.
  2. 18-70 years old
  3. Available for clinic visits for 48 weeks after study product administration.
  4. HIV-1 infected and clinically stable. [Note: Documented HIV-1 infection by HIV enzyme immunoassay (EIA) performed by a CLIA certified outside lab within 28 days of enrollment is acceptable.]
  5. At least one plasma viral load >=500 copies/mL within 28 days of enrollment. A plasma viral load within 28 days and closest to the day of enrollment, that is detectable but not greater than 100,000 copies/mL. [Note: outside laboratory results will be acceptable].
  6. A CD4+ count >=350 cells/mcL on 2 of 3 consecutive testing occasions (or on 2 of 2 sequential tests) within 28 days prior to enrollment. [Note: outside laboratory results will be acceptable].
  7. In general good health as assessed by a study clinician and under the care of a primary health care provider for medical management of HIV infection while participating in the study. Willing to give consent to contact and send laboratory results to the participant's primary health provider.
  8. Willing to have blood samples collected, stored indefinitely, and used for various research purposes.
  9. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  10. Screening laboratory values within 28 days prior to enrollment must meet the following criteria:
      • Absolute neutrophil count >=800/mcL
      • Platelets >=100,000/mcL
      • Hemoglobin >=10.0 g/dL
      • Creatinine less than or equal to 1.31 mg/dL
      • ALT less than or equal to 2.5 x ULN
      • Negative Hepatitis B Surface Antigen (HBsAg)
      • Undetectable Hepatitis C Viral Load (HCV RNA)
  
  [Note: Documented negative HBsAg and HCV RNA performed by an outside CLIA certified lab within 28 days of enrollment are acceptable.]
  Female-Specific Criteria:
• If a woman is sexually active with a male partner and has no history of hysterectomy, tubal ligation, or menopause, she must agree to use either a prescription birth control method or a barrier birth control method from the time of study enrollment until the last study visit, or have a monogamous partner who has had a vasectomy.
• Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential.

Exclusion Criteria:

A participant will be excluded if one or more of the following conditions apply:
• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational.
• Prior use of antiretroviral therapy.
• Ongoing AIDS-related opportunistic infection (including oral thrush).
• Active drug or alcohol use or dependence in the opinion of the site investigator that would interfere with adherence to study requirements.
• Any history of a severe allergic reaction, including generalized urticaria, angioedema or anaphylaxis prior to enrollment, that has a reasonable risk of recurrence during the study.
• Physical finding on examination considered clinically significant.
• Hypertension that is not well controlled.
• Weight >115 kg (253 pounds).
• Breast-feeding.
• Receipt of any investigational study product within 28 days prior to enrollment.
• Any other chronic or clinically significant medical condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02840474

Locations Show More

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

More Information

More Information

Additional Information:

NIH Clinical Center Detailed Web Page

Keywords provided by National Institutes of Health Clinical Center (CC):

HIV Viral Load
Antiviral
CD4 Count
HIV-1 Infection
Broadly Neutralizing Antibody

ClinicalTrials.gov processed this data on July 08, 2020
This information is provided by ClinicalTrials.gov.