Healthy Adult Immune Response Clinical Trial
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
| Verified date | December 2020 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 9 |
| Est. completion date | March 4, 2019 |
| Est. primary completion date | March 4, 2019 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years to 60 Years |
| Eligibility | - INCLUSION CRITERIA: 1. Willing and able to complete the informed consent process. 2. 18 to 60 years of age. 3. Based on history and examination, in good general health and without history of any of the conditions listed in the exclusion criteria. 4. Willing to have blood samples collected, stored indefinitely, and used for research purposes. 5. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. 6. Screening laboratory criteria within 84 days prior to enrollment must meet the following criteria: - 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. - EXCLUSION CRITERIA: 1. Woman who is breast-feeding, or planning to become pregnant during the study. 2. Prior receipt of licensed or investigational monoclonal antibody. 3. Weight > 115 kg. 4. 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. 5. Hypertension that is not well controlled. 6. Receipt of any investigational study agent within 28 days prior to enrollment. 7. 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
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. — View Citation
Kwon 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | 3 days after product administration | |
| Primary | 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. | 3 days after product administration | |
| Primary | 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. | Up to 24 weeks after product administration | |
| Primary | 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. | Up to 24 weeks after product administration | |
| Secondary | 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 |
Up to 24 weeks after product administration | |
| Secondary | 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 |
Up to 24 weeks after product administration | |
| Secondary | 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. |
Administration (0h) up to 28 days after product administration | |
| Secondary | 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. | Administration (0h) up to 28 days after product administration | |
| Secondary | 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. |
Administration (0h) up to 28 days after product administration | |
| Secondary | 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. |
Administration (0h) up to 28 days after product administration |