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Protocol Details

VRC 609: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously with or without Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

18-I-0105

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: 50 Years

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

Immune Cells;
bNAb;
Plasma Cell;
HIV;
Immunotherapy

Recruitment Keyword(s)

None

Condition(s)

HIV Antibodies

Investigational Drug(s)

VRC-HIVMAB091-00-AB

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: VRC-HIVMAB091-00-AB
Biological/Vaccine: EDP

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

The experimental product in this study, N6LS, is a human monoclonal antibody. Antibodies are one way that the human body fights infection. Monoclonal means that all the antibodies in the product are the same. N6LS is directed against the HIV virus. There is no HIV in the N6LS study product and you cannot get HIV from this product. This study will be the first time N6LS is tested in humans. It will be given into a vein in your arm (intravenously, IV) or as an injection underneath your skin (subcutaneously, SC). The study will also test N6LS mixed with an enzyme, rHuPH20 (recombinant human hyaluronidase). rHuPH20 increases the spread of fluids injected underneath your skin (subcutaneously, SC) and allows for the rapid delivery of large volume injections that can be given with a single needle. It will be given as a SC infusion using a small needle attached to an infusion pump. Study products will only be given to healthy adults who are not infected with HIV.

Objective:

The main purpose of the study is to see if N6LS alone and N6LS mixed with rHuPH20 is safe in healthy adults. Another goal is to learn how amounts of N6LS in the body change over time.

You may be eligible to participate if you are:

- 18 to 50 years old

- Willing to get N6LS or N6LS with rHuPH20

- Available for clinical follow-up for 6-11 months after enrollment

- Willing to donate blood to be stored indefinitely for research use

- In general good health

You will not be eligible to participate if you:

- Have received a licensed or investigational monoclonal antibody in the past

- Have a known sensitivity any ingredient in EDP

- Weigh more than 253 pounds (115 kg)

- Have HIV infection

Women must not be pregnant and must agree to use an effective method to prevent pregnancy during the entire study.

Study Plan:

32 to 40 healthy volunteers will be enrolled into 8 groups. Assigned study groups will depend on the dose of product, the numbers of times the product is given (once or three times at 12- week intervals), and how the product is given (IV or SC). Blood samples for research will be collected at most of the visits. There are about 14 clinic visits over 6 months for all groups getting one dose of product, and about 26 clinic visits over 12 months for the groups getting three doses of product. Participants will be compensated for their time and inconvenience.

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Eligibility

INCLUSION CRITERIA:

A subject must meet all of the following criteria:

1. Willing and able to complete the informed consent process.

2. 18 to 50 years of age.

3. Based on history and examination, must be 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).

- ALT: less than or equal to 1.25 x ULN.

- AST: less than or equal to 1.25 x ULN.

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

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:

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

1. Prior receipt of licensed or investigational monoclonal antibody.

2. Weight > 115 kg.

3. 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.

4. Hypertension that is not well controlled.

5. Woman who is breast-feeding, or planning to become pregnant during the study participation.

6. Receipt of any investigational study agent within 28 days prior to enrollment.

7. Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the subject including (but not limited to): diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of drug or alcohol abuse, asthma, autoimmune disease, infectious disease, psychiatric disorders, heart disease, or cancer.

8. Known hypersensitivity to hyaluronidase or any of the excipients in EDP.


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Citations:

Huang J, Kang BH, Ishida E, Zhou T, Griesman T, Sheng Z, Wu F, Doria-Rose NA, Zhang B, McKee K, O'Dell S, Chuang GY, Druz A, Georgiev IS, Schramm CA, Zheng A, Joyce MG, Asokan M, Ransier A, Darko S, Migueles SA, Bailer RT, Louder MK, Alam SM, Parks R, Kelsoe G, Von Holle T, Haynes BF, Douek DC, Hirsch V, Seaman MS, Shapiro L, Mascola JR, Kwong PD, Connors M. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. Immunity. 2016 Nov 15;45(5):1108-1121. doi: 10.1016/j.immuni.2016.10.027.

Gaudinski MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders JG, Holman LA, Gordon I, Plummer S, Hendel CS, Conan-Cibotti M, Lorenzo MG, Sitar S, Carlton K, Laurencot C, Bailer RT, Narpala S, McDermott AB, Namboodiri AM, Pandey JP, Schwartz RM, Hu Z, Koup RA, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE; VRC 606 Study Team. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018 Jan 24;15(1):e1002493. doi: 10.1371/journal.pmed.1002493. eCollection 2018 Jan.

Ledgerwood JE, Coates EE, Yamshchikov G, Saunders JG, Holman L, Enama ME, DeZure A, Lynch RM, Gordon I, Plummer S, Hendel CS, Pegu A, Conan-Cibotti M, Sitar S, Bailer RT, Narpala S, McDermott A, Louder M, O'Dell S, Mohan S, Pandey JP, Schwartz RM, Hu Z, Koup RA, Capparelli E, Mascola JR, Graham BS; VRC 602 Study Team. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol. 2015 Dec;182(3):289-301. doi: 10.1111/cei.12692. Epub 2015 Sep 24.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Richard L. Wu, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)



VRC Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center
National Institutes of Health (NIH)
Bethesda, MD 20892

(301) 451-8715
vaccines@nih.gov

VRC Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center
National Institutes of Health (NIH)
Bethesda, MD 20892

(301) 451-8715
vaccines@nih.gov

Clinical Trials Number:

NCT03538626

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