VRC 611: Human Monoclonal Antibody (mAb) VRC-HIVMAB0102-00-AB (CAP256V2LS)Administered Via Subcutaneous and Intravenous Injection in Healthy Adults

Overview

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. Researches 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 will be screened with a medical history, physical exam, and blood tests. Some will have a pregnancy test.

Participants will be assigned to one of two groups. Based on their group, they will get 1 dose of CAP256V2LS in 1 of 2 ways:

- Some participants will get CAP256V2LS as an infusion. A thin tube will be placed in an arm vein. CAP256V2LS will be given into the vein using a pump.

- Some participants will get CAP256V2LS injected under the skin. A small needle will inject CAP256V2LS into the fatty tissue of the belly, arm, or thigh. They will get 1 to 4 injections.

On the day they get CAP256V2LS, participants will give blood samples at different time points. This visit will last about 8 hours.

Participants will be asked to check their temperature every day for 7 days after receiving CAP256V2LS. They will use a tool to measure any redness, swelling, or bruising they may have at the injection site.

Participants will have visits at least 2-3 times during the first week after they get CAP256V2LS. Then they will have about 9 more visits over the next 6 months. Visits will include blood tests.

Full Title of Study: “VRC 611: A Phase I Safety and Pharmacokinetics Study to Evaluate a Human Monoclonal Antibody (mAb) VRC-HIVMAB0102-00-AB (CAP256V2S) Administered Via Subcutaneous and Intravenous Injection in Healthy Adults”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 28, 2021

Detailed Description

Design:

This first-in-human, open-label study will evaluate CAP256V2LS (VRC-HIVMAB0102-00-AB) in healthy adults. The primary hypothesis is that subcutaneous (SC) and intravenous (IV) administrations of CAP256V2LS will be safe and well-tolerated in healthy adults. A secondary hypothesis is that CAP256V2LS will be detectable in human sera with a definable half-life.

Study Product:

The 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. This bNAb was developed by the VRC/NIAID/NIH in collaboration with The Centre for the AIDS Programme of Research in South Africa (CAPRISA) and is manufactured under cGMP regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick. MD. The CAP256V2LS drug product is supplied at a concentration of 100 mg/mL in a sterile, aqueous, buffered solution of 6.25 mL in single-use 10 mL glass vials. R-Gene 10 will be added as a stabilizing agent to IV doses of CAP256V2LS. R-Gene10 (Arginine Hydrochloride Injection, USP) for intravenous infusion contains L-Arginine Hydrochloride, USP in Water for Injection (equivalent to a 10% solution).

Subjects:

Healthy subjects, 18-60 years of age

Study Plan:

This open-label study will include 2 dosing regimens with CAP256V2LS administered at 5 mg/kg IV and 5 mg/kg SC. A single dose of the study product will be administered on Day 0 as shown below.

VRC 611 Study Design

- Group 1

- Study Product: CAP256V2LS

- Subjects per Group: 5

- Dose (mg/kg) and Route Administered: 5 mg/kg IV

- Day 0: X

- Group 2

- Study Product: CAP256V2LS

- Subjects per Group: 5

- Dose (mg/kg) and Route Administered: 5 mg/kg SC

- Day 0: X

Total Subjects: 10 (Enrollment up to 20 subjects is permitted in case additional evaluations for safety or pharmacokinetic (PK) evaluations are needed.)

Duration:

Study participation will be approximately 24 weeks from the Day 0 product administration

Interventions

  • Biological: VRC-HIVMAB0102-00-AB
    • The 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 Cterminus of the heavy chain constant region designed to improve antibody half-life in vivo.

Arms, Groups and Cohorts

  • Experimental: Group 1
    • 5 mg/kg IV
  • Experimental: Group 2
    • 5 mg/kg SC

Clinical Trial Outcome Measures

Primary Measures

  • To evaluate the safety and tolerability of CAP256V2LS
    • Time Frame: Through 24 weeks after product administration
    • 5mg/kg IV of CAP256V2LS administered to healthy adults.
  • To evaluate the safety and tolerability of CAP256V2LS
    • Time Frame: Through 24 weeks after product administration
    • 5mg/kg SC of CAP256V2LS administered to healthy adults.

Secondary Measures

  • To evaluate the pharmacokinetics of CAP256V2LS
    • Time Frame: Throughout the study
    • The pharmacokinetics of CAP256V2LS administered.

Participating in This Clinical Trial

Inclusion Criteria

A subject must meet all of the following criteria to be included:

1. Able and willing to complete the informed consent process

2. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process

3. Available for clinical follow-up through the last study visit

4. 18 to 60 years of age

5. In good general health without clinically significant medical history

6. Physical examination without clinically significant findings within the 84 days prior to enrollment

7. Weight less than or equal to 115 kg

8. Willing to have blood samples collected, stored indefinitely, and used for research purposes

Laboratory Criteria within 84 days prior to enrollment:

9. White Blood Cell (WBC) 2,500-12,000/mm(3)

10. WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval

11. Platelets = 125,000 – 500,000/mm(3)

12. Hemoglobin within institutional normal range or accompanied by the PI or designee approval

13. Creatinine less than or equal to 1.1 x upper limit of normal (ULN) based on the institutional normal range

14. Alanine aminotransferase (ALT) less than or euqual to 1.25 x ULN based on the institutional normal range

15. Negative for HIV infection by an FDA approved method of detection

Criteria Specific to Women of Childbearing Potential:

16. Negative beta-HCG pregnancy test (urine or serum) on day of enrollment, and prior to product administration

17. Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the duration of study participation

Exclusion Criteria

A subject will be excluded if one or more of the following conditions apply:

1. Woman who is breast-feeding or planning to become pregnant during study participation

2. 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

3. Hypertension that is not well controlled

4. Receipt of any investigational study product within 28 days prior to enrollment

5. Receipt of any live attenuated vaccines within 28 days prior to enrollment

6. Prior receipt of a licensed or investigational monoclonal antibody

7. Prior receipt of an HIV vaccine

8. 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 subject s ability to give informed consent.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National Institute of Allergy and Infectious Diseases (NIAID)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Alicia T Widge, M.D., Principal Investigator, National Institute of Allergy and Infectious Diseases (NIAID)
  • Overall Contact(s)
    • VRC Clinic, (301) 451-8715, vaccines@nih.gov

References

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.

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.

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.

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