A Phase 1 Trial to Evaluate CAP256V2LS in Healthy Adults

NCT04408963 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 20009620-I-0096
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background: HIV is a serious disease with no cure or vaccine to prevent it. Using antibodies could be a way to prevent HIV infection. Antibodies are made by the human body to fight germs. Researchers want to test an antibody, CAP256V2LS. Objective: To test CAP256V2LS to see if it is safe and how the body responds to it. Eligibility: Healthy people, ages 18-60 Design: Participants were screened with a medical history, physical exam, and blood tests. Some females had a pregnancy test. Participants were assigned to one of two groups. Based on their group, they got 1 dose of CAP256V2LS in 1 of 2 ways:

• Some participants got CAP256V2LS as an infusion. A thin tube was placed in an arm vein and CAP256V2LS was given into the vein using a pump.
• Some participants got CAP256V2LS injected under the skin. A small needle was used to inject CAP256V2LS into the fatty tissue of the belly, arm, or thigh. They got 1 to 4 injections. On the day they got CAP256V2LS, participants gave blood samples at different time points. Participants were asked to check their temperature every day for 7 days after receiving CAP256V2LS. They used a tool to measure any redness, swelling, or bruising they may have at the site where they received the study drug. Participants had visits at least 2-3 times during the first week after they got CAP256V2LS. Then they had about 9 more visits over the next 6 months. Visits included blood tests.

Conditions

HIV

Keywords

HIV Prevention; Broadly-Neutralizing Human Monoclonal Antibodies; First in Human; Anti-Drug Antibody Response; Antibodies

Outcome Measures

Primary Outcomes (6)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of CAP256V2LS Product Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time 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 (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.

  7 days after CAP256V2LS product administration, at approximately Week 1

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of CAP256V2LS Product Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time 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 (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.

  7 days after CAP256V2LS product administration, at approximately Week 1

• Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following CAP256V2LS Product Administration

  Unsolicited adverse event (AE) data collection included AEs of all severities from the date of product administration through the Day 28 post-product administration visit. At other time periods greater than 4 weeks after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that required ongoing medical management (reported as a separate outcome) were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 through 4 weeks after CAP256V2LS Product Administration

• Number of Participants With Serious Adverse Events (SAEs) Following CAP256V2LS Product Administration

  SAEs were recorded from receipt of study product administration through the last expected study visit at Week 24. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 after CAP256V2LS product administration through the study participation, up to Week 24

• Number of Participants With New Chronic Medical Conditions Following CAP256V2LS Product Administration

  New chronic medical conditions that required ongoing medical management were recorded from receipt of first study product administration through the last expected study visit at Week 24. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 after CAP256V2LS product administration through the study participation, up to Week 24

• Number of Participants With Abnormal Laboratory Measures of Safety Following CAP256V2LS Product Administration

  Abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV) platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete Blood Count (CBC) with differential and Chemistry (ALT and creatinine) results were collected at different timepoints throughout the study per the protocol's schedule of evaluations. Comprehensive metabolic panel (CMP) was collected at baseline, and 2 weeks after product administration and as needed at additional timepoints. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used.

  Day 0 through 4 weeks after CAP256V2LS Product Administration

Secondary Outcomes (5)

• Pharmacokinetic (PK) Parameters of CAP256V2LS: Maximum Observed Serum Concentration (Cmax)

  Baseline through 24 weeks after CAP256V2LS product administration

• Pharmacokinetic (PK) Parameters of CAP256V2LS: Time to Reach Maximum Observed Serum Concentration (Tmax)

  Baseline through 24 weeks after CAP256V2LS product administration

• Pharmacokinetic (PK) Parameters of CAP256V2LS: Beta Half-life (T1/2b)

  Baseline through 24 weeks after CAP256V2LS product administration

• Pharmacokinetic (PK) Parameters of CAP256V2LS: Clearance Rate

  Baseline through 24 weeks after CAP256V2LS product administration

• Pharmacokinetic (PK) Parameters of CAP256V2LS: Volume of Distribution

  Baseline through 24 weeks after CAP256V2LS product administration

Study Arms (2)

Group 1: CAP256V2LS (5 mg/kg IV)

EXPERIMENTAL

CAP256V2LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0)

Biological: VRC-HIVMAB0102-00-AB

Group 2: CAP256V2LS (5 mg/kg SC)

EXPERIMENTAL

CAP256V2LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0)

Biological: VRC-HIVMAB0102-00-AB

Interventions

VRC-HIVMAB0102-00-AB BIOLOGICAL

The VRC-HIVMAB0102-00-AB (CAP256V2LS) broadly neutralizing monoclonal antibody (bNAb) targets the V1V2 region of the HIV-1 envelope, is human in origin, and contains two amino acid modifications within the C-terminus of the heavy chain constant region designed to improve antibody half-life in vivo.

Also known as: CAP256V2LS

Group 1: CAP256V2LS (5 mg/kg IV); Group 2: CAP256V2LS (5 mg/kg SC)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A volunteer must have met all of the following criteria to be included:
• Able and willing to complete the informed consent process
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
• Available for clinical follow-up through the last study visit
• to 60 years of age
• Based on medical history and physical examination, in good health and without clinically significant findings within 84 days prior to enrollment.
• Weight less than or equal to 115 kg
• Willing to have blood samples collected, stored indefinitely, and used for research purposes
• Laboratory Criteria within 84 days prior to enrollment:
• White Blood Cell (WBC) 2,500-12,000/mm\^3
• WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval
• Platelets = 125,000-500,000/mm\^3
• Hemoglobin within institutional normal range or accompanied by the PI or designee approval
• Creatinine less than or equal to 1.1 x upper limit of normal (ULN) based on the institutional normal range
• Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN based on the institutional normal range

You may not qualify if:

• A volunteer was excluded if one or more of the following conditions applied:
• Woman who is breast-feeding or planning to become pregnant during study participation
• Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the study
• Hypertension that is not well controlled
• Receipt of any live attenuated vaccines within 28 days prior to enrollment.
• Receipt of any vaccine within 2 weeks prior to enrollment/product administration
• Prior receipt of a licensed or investigational monoclonal antibody
• Prior receipt of an HIV vaccine
• Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ko SY, Pegu A, Rudicell RS, Yang ZY, Joyce MG, Chen X, Wang K, Bao S, Kraemer TD, Rath T, Zeng M, Schmidt SD, Todd JP, Penzak SR, Saunders KO, Nason MC, Haase AT, Rao SS, Blumberg RS, Mascola JR, Nabel GJ. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature. 2014 Oct 30;514(7524):642-5. doi: 10.1038/nature13612. Epub 2014 Aug 13.

  PMID: 25119033 BACKGROUND

• Doria-Rose NA, Schramm CA, Gorman J, Moore PL, Bhiman JN, DeKosky BJ, Ernandes MJ, Georgiev IS, Kim HJ, Pancera M, Staupe RP, Altae-Tran HR, Bailer RT, Crooks ET, Cupo A, Druz A, Garrett NJ, Hoi KH, Kong R, Louder MK, Longo NS, McKee K, Nonyane M, O'Dell S, Roark RS, Rudicell RS, Schmidt SD, Sheward DJ, Soto C, Wibmer CK, Yang Y, Zhang Z; NISC Comparative Sequencing Program; Mullikin JC, Binley JM, Sanders RW, Wilson IA, Moore JP, Ward AB, Georgiou G, Williamson C, Abdool Karim SS, Morris L, Kwong PD, Shapiro L, Mascola JR. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature. 2014 May 1;509(7498):55-62. doi: 10.1038/nature13036. Epub 2014 Mar 2.

  PMID: 24590074 BACKGROUND

• Doria-Rose NA, Bhiman JN, Roark RS, Schramm CA, Gorman J, Chuang GY, Pancera M, Cale EM, Ernandes MJ, Louder MK, Asokan M, Bailer RT, Druz A, Fraschilla IR, Garrett NJ, Jarosinski M, Lynch RM, McKee K, O'Dell S, Pegu A, Schmidt SD, Staupe RP, Sutton MS, Wang K, Wibmer CK, Haynes BF, Abdool-Karim S, Shapiro L, Kwong PD, Moore PL, Morris L, Mascola JR. New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency. J Virol. 2015 Oct 14;90(1):76-91. doi: 10.1128/JVI.01791-15. Print 2016 Jan 1.

  PMID: 26468542 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Results Point of Contact

• Title: VRC Clinical Trials Program Leadership
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

ctpleadership@mail.nih.gov

301-451-8715

Study Officials

• Richard L Wu, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 1, 2020
• Study Start: March 22, 2022
• Primary Completion: November 28, 2022
• Study Completion: November 28, 2022
• Last Updated: January 11, 2024
• Results First Posted: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)