Healthy Adult Immune ResponsePhase 1NCT03565315
Phase I Study to Evaluate a Human Monoclonal Antibody (MAb) 10E8VLS Administered Alone or Concurrently With MAb VRC07-523LS Via Subcutaneous Injection in Healthy Adults
A Phase 1 study testing VRC-HIVMAB095-00-AB (10E8VLS) and VRC-HIVMAB075-00-AB (VRC07-523LS) in people with Healthy Adult Immune Response, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Human immunodeficiency virus (HIV) infection is a serious disease. There is no cure or vaccine to prevent infection. Using antibodies might be a good way to treat or prevent HIV. Antibodies are naturally made by the body to fight germs. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult Immune Response
- What is being tested?
- VRC-HIVMAB095-00-AB (10E8VLS) and VRC-HIVMAB075-00-AB (VRC07-523LS)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jul 2018to 4 Mar 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing and able to complete the informed consent process.
- 18 to 60 years of age.
- Based on history and examination, in good general health and without history of any of the conditions listed in the exclusion criteria.
- Willing to have blood samples collected, stored indefinitely, and used for research purposes.
- Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- Screening laboratory criteria within 84 days prior to enrollment must meet the following criteria:
Show all 18Show fewer
- White blood cell count (WBC): 2,500-12,000/mm^3.
- WBC differential: Within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
- Platelets: 125,000 - 400,000/mm^3.
- Hemoglobin: Within institutional normal range or accompanied by PI or designee approval.
- Creatinine: less than or equal to 1.1 x Upper Limit of Normal (ULN).
- Aspartate aminotransferase (AST): less than or equal to 1.25 x ULN
- Alanine aminotransferase (ALT): less than or equal to 1.25 x ULN.
- Negative for HIV infection by an FDA approved method of detection.
- Negative for Hepatitis B core antibody (HBcAb) and Hepatitis C virus antibody (HCV Ab).
- Female-Specific Criteria:
- 7. If a woman is of reproductive potential and sexually active with a male partner, then she agrees to use an effective means of birth control from the time of study enrollment until the last study visit, or to be monogamous with a partner who has had a vasectomy.
- 8. Negative Beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential.
Who cannot join
- Woman who is breast-feeding, or planning to become pregnant during the study.
- Prior receipt of licensed or investigational monoclonal antibody.
- Weight > 115 kg.
- Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis within the 2 years prior to enrollment that has a reasonable risk of recurrence during the study.
- Hypertension that is not well controlled.
- Receipt of any investigational study agent within 28 days prior to enrollment.
- Any other chronic or clinically significant condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer including (but not limited to): diabetes mellitus type I/II, chronic hepatitis; OR clinically significant forms of drug or alcohol abuse, asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: VRC 610: Phase I Safety and Pharmacokinetics Study to Evaluate a Human Monoclonal Antibody (MAB) VRC-HIVMAB095-00-AB (10E8VLS) Administered Alone or Concurrently With MAB VRC-HIVMAB075-00-AB (VRC07-523LS) Via Subcutaneous Injection in Healthy Adults
Background:
Human immunodeficiency virus (HIV) infection is a serious disease. There is no cure or vaccine to prevent infection. Using antibodies might be a good way to treat or prevent HIV. Antibodies are naturally made by the body to fight germs. Researchers want to test if two antibodies made artificially in a lab can help to prevent HIV infection. The antibodies are 10E8VLS and VRC07-523LS.
Read more
Objective:
To see if 10E8VLS and VRC07-523LS are safe and well-tolerated and how long they stay in the blood.
Eligibility:
Healthy adults ages 18-60
Design:
Volunteers were screened in another protocol.
Participants were enrolled in 1 of 4 groups:
Group 1 participants were enrolled to receive 1 dose of 10E8VLS.
Group 2 participants were enrolled to receive 3 doses of 10E8VLS.
Group 3 participants were enrolled to receive 1 dose of both 10E8VLS and VRC07-523LS.
Group 4 participants were enrolled to receive 3 doses of both 10E8VLS and VRC07-523LS.
Participants in Groups 1 and 3 were expected to be enrolled about 13 visits over 24 weeks.
Participants in Groups 2 and 4 were expected to be enrolled about 26 visits over 48 weeks.
Participants were weighed before each dose. Women may have had a pregnancy test. Participants had blood collected.
A small needle injected each dose into fatty tissue of the belly, upper arm, or thigh. Participants received between 1 and 8 injections per dose depending on their weight. Heavier participants received more injections.
Participants received a ruler and thermometer. They checked their temperature for 3 days after injection(s) and measured any redness, swelling, or bruising at the injection site.
At non-injection visits, participants had blood drawn and were checked for health changes or problems.
Read the detailed description
VRC 610:
A Phase I Safety and Pharmacokinetics Study to Evaluate a Human Monoclonal Antibody (MAB) VRC-HIVMAB095-00-AB (10E8VLS) Administered Alone or Concurrently with MAB VRC-HIVMAB075-00-AB (VRC07-523LS) Via Subcutaneous Injection in Healthy Adults
Study Design:
This first-in-human, open-label study evaluated MAb 10E8VLS (VRC-HIVMAB095-00-AB) administered alone or concurrently (i.e., at the same visit) with MAb VRC07-523LS (VRC-HIVMAB075-00-AB) in healthy adults ages 18 to 60. The primary hypothesis was that administrations of 10E8VLS alone and concurrently with VRC07-523LS will be well-tolerated in healthy adults. A secondary hypothesis was that both broadly neutralizing monoclonal antibodies (bNAbs) will be detectable in human sera with a definable half-life.
Product Description:
The 10E8VLS and VRC07-523LS bNAbs target the HIV-1 envelope at distinct epitopes: 10E8VLS recognizes the membrane proximal external region (MPER) and proximal viral membrane lipid of gp41, while VRC07-523LS recognizes the CD4 binding site of gp120. Both antibodies are human in origin, contain two amino acid modifications within the C-terminus of the heavy chain constant region designed to improve antibody half-life in vivo, and were developed by the VRC/NIAID/NIH. The 10E8VLS and VRC07-523LS bNAbs were manufactured under current Good Manufacturing Practice (cGMP) regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD.
The 10E8VLS drug product was supplied at a concentration of 100 mg/mL in a sterile, aqueous, buffered solution of 5.25 mL in single-use 10 mL glass vials. The VRC07-523LS drug product was supplied at a concentration of 100 mg/mL in an isotonic, sterile solution of 6.25 mL in single-use 10 mL glass vials. Each drug product was prepared for administration in separate syringes.
Participants:
Healthy adults, 18-60 years of age.
Study Plan:
This open-label study included 4 dosing regimens of either 10E8VLS (5 mg/kg) administered alone or 10E8VLS (5 mg/kg) and VRC07-523LS (5 mg/kg). All injections were administered by the subcutaneous (SC) route. For Groups 1 and 2, 10E8VLS was to be administered once or three-times at 12-week intervals. For Groups 3 and 4, 10E8VLS and VRC07-523LS were to be administered once or three-times at 12-week intervals, respectively. Enrollment began with Groups 1 and 2, followed by Groups 3 and 4.
VRC 610 Study Schema:
- Group 1; Study Product: 10E8VLS; Planned Participants per Group: 3; Dose Administered SC: 5 mg/kg; Day 0
- Group 2; Study Product: 10E8VLS; Planned Participants per Group: 3; Dose Administered SC: 5 mg/kg; Day 0, Week 12*, Week 24*
- Group 3 (a,b); Study Product: 10E8VLS+VRC07-523LS; Planned Participants per Group: 5; Dose Administered SC: 5 mg/kg of each MAb; Day 0
- Group 4 (a,b); Study Product: 10E8VLS+VRC07-523LS; Planned Participants per Group: 5; Dose Administered SC: 5 mg/kg of each MAb; Day 0, Week 12*, Week 24*
- Total Planned Participants = 16
- Total Actual Participants = 9 (c) (*)Participants received only one product administration on Day 0 because of the voluntary study pause and termination by Investigational New Drug (IND) Sponsor/Principal Investigator (PI) decision.
- Enrollment into Group 3 and 4 commenced after positive protocol safety review team (PSRT) review of safety data from Groups 1 and 2
- 10E8VLS and VRC07-523LS were provided in separate syringes and administered at the same visit.
- The expected enrollment was 16 participants; however, enrollment was voluntarily paused by the IND Sponsor/PI and the study ultimately stopped after several Grade 2 and Grade 3 redness local reactogenicity reactions were observed at 10E8VLS injection sites.
Study Duration:
Study participation was expected to be approximately 24 weeks for participants in Groups 1 and 3, and 48 weeks for participants in Groups 2 and 4. Participants in the repeat-dose groups (2 and 4) were converted to a modified schedule per protocol. Study participation for all participants was approximately 24 weeks after Day 0 product administration.
- Conditions
- Healthy Adult Immune Response
- Being tested
- VRC-HIVMAB095-00-AB (10E8VLS), VRC-HIVMAB075-00-AB (VRC07-523LS)
- Keywords
- HIV Prevention, Broadly Neutralizing Monoclonal Antibodies, First in Human Study, Anti-Drug Antibody Response to 10E8VLS or VRC07-523LS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VRC-HIVMAB095-00-AB (10E8VLS)Biological
10E8VLS is an investigational Monoclonal Antibody targeted to the membrane proximal external region and proximal viral membrane lipid region of HIV-1.
VRC-HIVMAB075-00-AB (VRC07-523LS)Biological
VRC07-523LS is an investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: 10E8VLS (5 mg/kg) SC Single Dose Group | Experimental | 10E8VLS (5 mg/kg) administered by the subcutaneous (SC) route (Day 0) Receives: Biological: VRC-HIVMAB095-00-AB (10E8VLS) |
| Group 2: 10E8VLS (5 mg/kg) SC Multiple Dose Group* (*Only One Dose Received) | Experimental | 10E8VLS (5 mg/kg) administered by the SC route (Day 0, Week 12*, Week 24*)
*Participants received only one product administration on Day 0 because of the voluntary study pause and termination by the IND Sponsor/PI decision. Receives: Biological: VRC-HIVMAB095-00-AB (10E8VLS) |
| Group 3: 10E8VLS+VRC07-523LS (5 mg/kg each) SC Single Dose Group | Experimental | 10E8VLS (5 mg/kg)+VRC07-523LS (5 mg/kg) administered by the SC route (Day 0) Receives: Biological: VRC-HIVMAB095-00-AB (10E8VLS); Biological: VRC-HIVMAB075-00-AB (VRC07-523LS) |
| Group 4: 10E8VLS+VRC07-523LS (5 mg/kg each) SC Multiple Dose Group* (*Only One Dose Received) | Experimental | 10E8VLS (5 mg/kg)+VRC07-523LS (5 mg/kg) administered by the SC route (Day 0, Week 12*, Week 24*)
*Participants received only one product administration on Day 0 because of the voluntary study pause and termination by the IND Sponsor/PI decision. Receives: Biological: VRC-HIVMAB095-00-AB (10E8VLS); Biological: VRC-HIVMAB075-00-AB (VRC07-523LS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of Product Administration
Local symptoms were recorded by participants using a 3-day diary. Solicited local symptoms include pain/tenderness, bruising, redness, swelling, and pruritus (itchiness) at the product administration site. Clinicians reviewed the diary with the participant and collected resolution information for any symptoms that were not resolved within 3 days. Participants were counted once for each symptom at the worst severity if they experienced the symptom at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
Measured: 3 days after product administration
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Product Administration
Participants recorded 3-day systemic symptoms in a diary after each study product administration. Solicited systemic symptoms include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, temperature and joint pain. Participants recorded highest measured temperature daily. Clinicians reviewed the diary with the participant and collected resolution information for any symptoms that were not resolved within 3 days. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
Measured: 3 days after product administration
Number of Participants With One or More Unsolicited Non-Serious Adverse Events
Unsolicited adverse events (AEs) collected during the period from study product administration at Day 0 through 56 days after product administration. After the indicated time period through the last expected study visit at 24 weeks after product administration, only new chronic medical conditions collected as unsolicited AEs. The number reported is the number of participants who experienced at least one AE in the reporting period. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Measured: Up to 24 weeks after product administration
Number of Participants With Serious Adverse Events
Serious adverse events (SAEs) collected during the period from study product administration at Day 0 through 24 weeks after the product administration.
Measured: Up to 24 weeks after product administration
Secondary outcomes (6)
Maximum Observed Serum Concentration (Cmax) of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Cmax is the peak serum concentration that 10E8VLS achieves after it has been administered: it is determined as maximum value on the summary pharmacokinetic (PK) curve for the overall study population.
Serum was collected at the following time points: Groups 1 and 3: Pre-injection (baseline), and 24, 48 and 72 hours post injection, followed by Weeks 1-4, 8, 12, 16, 20 and 24 post-injection; Groups 2 and 4: Pre-injection (baseline), and 24, 48 and 72 hours post injection, and Weeks 1, 2, 4, 8, 12-14, 16, 20 and 24 post injection
Measured: Up to 24 weeks after product administration
Time to Reach Maximum Observed Serum Concentration (Tmax) of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Tmax is the time it takes to reach Cmax of 10E8VLS after it has been administered; it is determined based on the summary PK curve for the overall study population.
Serum was collected at the following time points: Groups 1 and 3: Pre-injection (baseline), and 24, 48 and 72 hours post injection, followed by Weeks 1-4, 8, 12, 16, 20 and 24 post-injection; Groups 2 and 4: Pre-injection (baseline), and 24, 48 and 72 hours post injection, and Weeks 1, 2, 4, 8, 12-14, 16, 20 and 24 post injection
Measured: Up to 24 weeks after product administration
Area Under the Curve (AUC0-28D) of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
The AUC0-28D represents the total drug exposure in 28 days after 10E8VLS administration; it is determined based on the summary PK curve for the overall study population.
Serum was collected at the following time points: Groups 1 and 3: Pre-injection (baseline), and 24, 48 and 72 hours post injection, followed by Weeks 1, 2, 3 and 4 post injection; Groups 2 and 4: Pre-injection (baseline) and 24, 48 and 72 hours post injection and Weeks 1, 2 and 4 post injection.
Measured: Administration (0h) up to 28 days after product administration
4 Week Mean Serum Concentration of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
The mean of individual participant 10E8VLS serum concentrations. The overall population was analyzed as all participants received only one 10E8VLS administration.
Measured: Administration (0h) up to 28 days after product administration
Clearance Rate of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Rate of 10E8VLS elimination divided by the plasma 10E8VLS concentration; determined based on the summary PK curve for the overall study population.
Serum was collected at the following time points: Groups 1 and 3: Pre-injection (baseline), and 24, 48 and 72 hours post injection, followed by Weeks 1, 2, 3 and 4 post injection; Groups 2 and 4: Pre-injection (baseline) and 24, 48 and 72 hours post injection and Weeks 1, 2 and 4 post injection.
Measured: Administration (0h) up to 28 days after product administration
Overall Half-Life (T1/2) of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.
Serum was collected at the following time points: Groups 1 and 3: Pre-injection (baseline), and 24, 48 and 72 hours post injection, followed by Weeks 1, 2, 3 and 4 post injection; Groups 2 and 4: Pre-injection (baseline) and 24, 48 and 72 hours post injection and Weeks 1, 2 and 4 post injection.
Measured: Administration (0h) up to 28 days after product administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2018
- Study start10 Jul 2018
- Primary completion4 Mar 2019
- Study completion4 Mar 2019
Why it stopped: Sponsor/PI voluntarily paused and stopped study after observing several Grade 2 and Grade 3 redness local reactogenicity reactions at 10E8VLS injection sites
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Healthy Adult Immune ResponseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Martin R Gaudinski, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03565315
- Sponsor's protocol ID
- 180113
- Other IDs
- 18-I-0113
- Status last verified
- Dec 2020
- First submitted
- 19 Jun 2018
- Last updated
- 30 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, Imamichi H, Bailer RT, Chakrabarti B, Sharma SK, Alam SM, Wang T, Yang Y, Zhang B, Migueles SA, Wyatt R, Haynes BF, Kwong PD, Mascola JR, Connors M. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature. 2012 Nov 15;491(7424):406-12. doi: 10.1038/nature11544. Epub 2012 Sep 18.
PubMed 23151583Kwon YD, Georgiev IS, Ofek G, Zhang B, Asokan M, Bailer RT, Bao A, Caruso W, Chen X, Choe M, Druz A, Ko SY, Louder MK, McKee K, O'Dell S, Pegu A, Rudicell RS, Shi W, Wang K, Yang Y, Alger M, Bender MF, Carlton K, Cooper JW, Blinn J, Eudailey J, Lloyd K, Parks R, Alam SM, Haynes BF, Padte NN, Yu J, Ho DD, Huang J, Connors M, Schwartz RM, Mascola JR, Kwong PD. Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design. J Virol. 2016 Jun 10;90(13):5899-5914. doi: 10.1128/JVI.03246-15. Print 2016 Jul 1.
PubMed 27053554Awan SF, Pegu A, Strom L, Carter CA, Hendel CS, Holman LA, Costner PJ, Trofymenko O, Dyer R, Gordon IJ, Rothwell RSS, Hickman SP, Conan-Cibotti M, Doria-Rose NA, Lin BC, O'Connell S, Narpala SR, Almasri CG, Liu C, Ko S, Kwon YD, Namboodiri AM, Pandey JP, Arnold FJ, Carlton K, Gall JG, Kwong PD, Capparelli EV, Bailer RT, McDermott AB, Chen GL, Koup RA, Mascola JR, Coates EE, Ledgerwood JE, Gaudinski MR; VRC 610 study team. Phase 1 trial evaluating safety and pharmacokinetics of HIV-1 broadly neutralizing mAbs 10E8VLS and VRC07-523LS. JCI Insight. 2024 Apr 8;9(7):e175375. doi: 10.1172/jci.insight.175375.
PubMed 38587079
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VRC 610: Phase I Safety and Pharmacokinetics Study to Evaluate a Human Monoclonal Antibody (MAB) VRC-HIVMAB095-00-AB (10E8VLS) Administered Alone or Concurrently With MAB VRC-HIVMAB075-00-AB (VRC07-523LS) Via Subcutaneous Injection in Healthy Adults
- ClinicalTrials.gov ID
- NCT03565315
- Acronym / sponsor ID
- 180113
- Conditions
- Healthy Adult Immune Response
- Keywords
- HIV Prevention, Broadly Neutralizing Monoclonal Antibodies, First in Human Study, Anti-Drug Antibody Response to 10E8VLS or VRC07-523LS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor/PI voluntarily paused and stopped study after observing several Grade 2 and Grade 3 redness local reactogenicity reactions at 10E8VLS injection sites
- Enrolment
- 9 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 10 Jul 2018 (actual)
- Primary completion
- 4 Mar 2019 (actual)
- Study completion
- 4 Mar 2019 (actual)
- First posted
- 21 Jun 2018 (actual)
- Results
- Posted 30 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Human immunodeficiency virus (HIV) infection is a serious disease. There is no cure or vaccine to prevent infection. Using antibodies might be a good way to treat or prevent HIV. Antibodies are naturally made by the body to fight germs. Researchers want to test if two antibodies made artificially in a lab can help to prevent HIV infection. The antibodies are 10E8VLS and VRC07-523LS.
Objective:
To see if 10E8VLS and VRC07-523LS are safe and well-tolerated and how long they stay in the blood.
Eligibility:
Healthy adults ages 18-60
Design:
Volunteers were screened in another protocol.
Participants were enrolled in 1 of 4 groups:
Group 1 participants were enrolled to receive 1 dose of 10E8VLS.
Group 2 participants were enrolled to receive 3 doses of 10E8VLS.
Group 3 participants were enrolled to receive 1 dose of both 10E8VLS and VRC07-523LS.
Group 4 participants were enrolled to receive 3 doses of both 10E8VLS and VRC07-523LS.
Participants in Groups 1 and 3 were expected to be enrolled about 13 visits over 24 weeks.
Participants in Groups 2 and 4 were expected to be enrolled about 26 visits over 48 weeks.
Participants were weighed before each dose. Women may have had a pregnancy test. Participants had blood collected.
A small needle injected each dose into fatty tissue of the belly, upper arm, or thigh. Participants received between 1 and 8 injections per dose depending on their weight. Heavier participants received more injections.
Participants received a ruler and thermometer. They checked their temperature for 3 days after injection(s) and measured any redness, swelling, or bruising at the injection site.
At non-injection visits, participants had blood drawn and were checked for health changes or problems.
Detailed description
VRC 610:
A Phase I Safety and Pharmacokinetics Study to Evaluate a Human Monoclonal Antibody (MAB) VRC-HIVMAB095-00-AB (10E8VLS) Administered Alone or Concurrently with MAB VRC-HIVMAB075-00-AB (VRC07-523LS) Via Subcutaneous Injection in Healthy Adults
Study Design:
This first-in-human, open-label study evaluated MAb 10E8VLS (VRC-HIVMAB095-00-AB) administered alone or concurrently (i.e., at the same visit) with MAb VRC07-523LS (VRC-HIVMAB075-00-AB) in healthy adults ages 18 to 60. The primary hypothesis was that administrations of 10E8VLS alone and concurrently with VRC07-523LS will be well-tolerated in healthy adults. A secondary hypothesis was that both broadly neutralizing monoclonal antibodies (bNAbs) will be detectable in human sera with a definable half-life.
Product Description:
The 10E8VLS and VRC07-523LS bNAbs target the HIV-1 envelope at distinct epitopes: 10E8VLS recognizes the membrane proximal external region (MPER) and proximal viral membrane lipid of gp41, while VRC07-523LS recognizes the CD4 binding site of gp120. Both antibodies are human in origin, contain two amino acid modifications within the C-terminus of the heavy chain constant region designed to improve antibody half-life in vivo, and were developed by the VRC/NIAID/NIH. The 10E8VLS and VRC07-523LS bNAbs were manufactured under current Good Manufacturing Practice (cGMP) regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD.
The 10E8VLS drug product was supplied at a concentration of 100 mg/mL in a sterile, aqueous, buffered solution of 5.25 mL in single-use 10 mL glass vials. The VRC07-523LS drug product was supplied at a concentration of 100 mg/mL in an isotonic, sterile solution of 6.25 mL in single-use 10 mL glass vials. Each drug product was prepared for administration in separate syringes.
Participants:
Healthy adults, 18-60 years of age.
Study Plan:
This open-label study included 4 dosing regimens of either 10E8VLS (5 mg/kg) administered alone or 10E8VLS (5 mg/kg) and VRC07-523LS (5 mg/kg). All injections were administered by the subcutaneous (SC) route. For Groups 1 and 2, 10E8VLS was to be administered once or three-times at 12-week intervals. For Groups 3 and 4, 10E8VLS and VRC07-523LS were to be administered once or three-times at 12-week intervals, respectively. Enrollment began with Groups 1 and 2, followed by Groups 3 and 4.
VRC 610 Study Schema:
- Group 1; Study Product: 10E8VLS; Planned Participants per Group: 3; Dose Administered SC: 5 mg/kg; Day 0
- Group 2; Study Product: 10E8VLS; Planned Participants per Group: 3; Dose Administered SC: 5 mg/kg; Day 0, Week 12*, Week 24*
- Group 3 (a,b); Study Product: 10E8VLS+VRC07-523LS; Planned Participants per Group: 5; Dose Administered SC: 5 mg/kg of each MAb; Day 0
- Group 4 (a,b); Study Product: 10E8VLS+VRC07-523LS; Planned Participants per Group: 5; Dose Administered SC: 5 mg/kg of each MAb; Day 0, Week 12*, Week 24*
- Total Planned Participants = 16
- Total Actual Participants = 9 (c) (*)Participants received only one product administration on Day 0 because of the voluntary study pause and termination by Investigational New Drug (IND) Sponsor/Principal Investigator (PI) decision.
- Enrollment into Group 3 and 4 commenced after positive protocol safety review team (PSRT) review of safety data from Groups 1 and 2
- 10E8VLS and VRC07-523LS were provided in separate syringes and administered at the same visit.
- The expected enrollment was 16 participants; however, enrollment was voluntarily paused by the IND Sponsor/PI and the study ultimately stopped after several Grade 2 and Grade 3 redness local reactogenicity reactions were observed at 10E8VLS injection sites.
Study Duration:
Study participation was expected to be approximately 24 weeks for participants in Groups 1 and 3, and 48 weeks for participants in Groups 2 and 4. Participants in the repeat-dose groups (2 and 4) were converted to a modified schedule per protocol. Study participation for all participants was approximately 24 weeks after Day 0 product administration.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1: 10E8VLS (5 mg/kg) SC Single Dose Group | Experimental | Biological: VRC-HIVMAB095-00-AB (10E8VLS)10E8VLS (5 mg/kg) administered by the subcutaneous (SC) route (Day 0) |
| Group 2: 10E8VLS (5 mg/kg) SC Multiple Dose Group* (*Only One Dose Received) | Experimental | Biological: VRC-HIVMAB095-00-AB (10E8VLS)10E8VLS (5 mg/kg) administered by the SC route (Day 0, Week 12*, Week 24*) *Participants received only one product administration on Day 0 because of the voluntary study pause and termination by the IND Sponsor/PI decision. |
| Group 3: 10E8VLS+VRC07-523LS (5 mg/kg each) SC Single Dose Group | Experimental | Biological: VRC-HIVMAB095-00-AB (10E8VLS), Biological: VRC-HIVMAB075-00-AB (VRC07-523LS)10E8VLS (5 mg/kg)+VRC07-523LS (5 mg/kg) administered by the SC route (Day 0) |
| Group 4: 10E8VLS+VRC07-523LS (5 mg/kg each) SC Multiple Dose Group* (*Only One Dose Received) | Experimental | Biological: VRC-HIVMAB095-00-AB (10E8VLS), Biological: VRC-HIVMAB075-00-AB (VRC07-523LS)10E8VLS (5 mg/kg)+VRC07-523LS (5 mg/kg) administered by the SC route (Day 0, Week 12*, Week 24*) *Participants received only one product administration on Day 0 because of the voluntary study pause and termination by the IND Sponsor/PI decision. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- White blood cell count (WBC): 2,500-12,000/mm^3.
- WBC differential: Within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
- Platelets: 125,000 - 400,000/mm^3.
- Hemoglobin: Within institutional normal range or accompanied by PI or designee approval.
- Creatinine: less than or equal to 1.1 x Upper Limit of Normal (ULN).
Key exclusion criteria (7 listed)
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 |
|---|---|---|
| VRC-HIVMAB095-00-AB (10E8VLS)10E8VLS is an investigational Monoclonal Antibody targeted to the membrane proximal external region and proximal viral membrane lipid region of HIV-1. | Biological | Group 1: 10E8VLS (5 mg/kg) SC Single Dose Group, Group 2: 10E8VLS (5 mg/kg) SC Multiple Dose Group* (*Only One Dose Received), Group 3: 10E8VLS+VRC07-523LS (5 mg/kg each) SC Single Dose Group, Group 4: 10E8VLS+VRC07-523LS (5 mg/kg each) SC Multiple Dose Group* (*Only One Dose Received) |
| VRC-HIVMAB075-00-AB (VRC07-523LS)VRC07-523LS is an investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1. | Biological | Group 3: 10E8VLS+VRC07-523LS (5 mg/kg each) SC Single Dose Group, Group 4: 10E8VLS+VRC07-523LS (5 mg/kg each) SC Multiple Dose Group* (*Only One Dose Received) |
Primary outcome
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of Product Administration
Time frame: 3 days after product administration
Local symptoms were recorded by participants using a 3-day diary. Solicited local symptoms include pain/tenderness, bruising, redness, swelling, and pruritus (itchiness) at the product administration site. Clinicians reviewed the diary with the participant and collected resolution information for any symptoms that were not resolved within 3 days. Participants were counted once for each symptom at the worst severity if they experienced the symptom at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Product Administration
Time frame: 3 days after product administration
Participants recorded 3-day systemic symptoms in a diary after each study product administration. Solicited systemic symptoms include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, temperature and joint pain. Participants recorded highest measured temperature daily. Clinicians reviewed the diary with the participant and collected resolution information for any symptoms that were not resolved within 3 days. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
Number of Participants With One or More Unsolicited Non-Serious Adverse Events
Time frame: Up to 24 weeks after product administration
Unsolicited adverse events (AEs) collected during the period from study product administration at Day 0 through 56 days after product administration. After the indicated time period through the last expected study visit at 24 weeks after product administration, only new chronic medical conditions collected as unsolicited AEs. The number reported is the number of participants who experienced at least one AE in the reporting period. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With Serious Adverse Events
Time frame: Up to 24 weeks after product administration
Serious adverse events (SAEs) collected during the period from study product administration at Day 0 through 24 weeks after the product administration.
6 secondary outcomes
Maximum Observed Serum Concentration (Cmax) of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Time frame: Up to 24 weeks after product administration
Time to Reach Maximum Observed Serum Concentration (Tmax) of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Time frame: Up to 24 weeks after product administration
Area Under the Curve (AUC0-28D) of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Time frame: Administration (0h) up to 28 days after product administration
4 Week Mean Serum Concentration of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Time frame: Administration (0h) up to 28 days after product administration
Clearance Rate of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Time frame: Administration (0h) up to 28 days after product administration
Overall Half-Life (T1/2) of 10E8VLS Administered Alone or Concurrently With VRC07-523LS
Time frame: Administration (0h) up to 28 days after product administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23151583Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, Imamichi H, Bailer RT, Chakrabarti B, Sharma SK, Alam SM, Wang T, Yang Y, Zhang B, Migueles SA, Wyatt R, Haynes BF, Kwong PD, Mascola JR, Connors M. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature. 2012 Nov 15;491(7424):406-12. doi: 10.1038/nature11544. Epub 2012 Sep 18.
- Background: PubMed 27053554Kwon YD, Georgiev IS, Ofek G, Zhang B, Asokan M, Bailer RT, Bao A, Caruso W, Chen X, Choe M, Druz A, Ko SY, Louder MK, McKee K, O'Dell S, Pegu A, Rudicell RS, Shi W, Wang K, Yang Y, Alger M, Bender MF, Carlton K, Cooper JW, Blinn J, Eudailey J, Lloyd K, Parks R, Alam SM, Haynes BF, Padte NN, Yu J, Ho DD, Huang J, Connors M, Schwartz RM, Mascola JR, Kwong PD. Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design. J Virol. 2016 Jun 10;90(13):5899-5914. doi: 10.1128/JVI.03246-15. Print 2016 Jul 1.
- Derived from this study: PubMed 38587079Awan SF, Pegu A, Strom L, Carter CA, Hendel CS, Holman LA, Costner PJ, Trofymenko O, Dyer R, Gordon IJ, Rothwell RSS, Hickman SP, Conan-Cibotti M, Doria-Rose NA, Lin BC, O'Connell S, Narpala SR, Almasri CG, Liu C, Ko S, Kwon YD, Namboodiri AM, Pandey JP, Arnold FJ, Carlton K, Gall JG, Kwong PD, Capparelli EV, Bailer RT, McDermott AB, Chen GL, Koup RA, Mascola JR, Coates EE, Ledgerwood JE, Gaudinski MR; VRC 610 study team. Phase 1 trial evaluating safety and pharmacokinetics of HIV-1 broadly neutralizing mAbs 10E8VLS and VRC07-523LS. JCI Insight. 2024 Apr 8;9(7):e175375. doi: 10.1172/jci.insight.175375.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- 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.
Martin R Gaudinski, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
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 VRC-HIVMAB095-00-AB (10E8VLS) and VRC-HIVMAB075-00-AB (VRC07-523LS) in people with Healthy Adult Immune Response, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 18 inclusion and 7 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: stopped early, as of the sponsor's last update on 30 Dec 2020. 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 United States. 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?
Yes. Results are posted in the registry (first posted 30 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of Product Administration (time frame: 3 days after product administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03565315, which also lists 3 linked publications.
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 30 Dec 2020.