NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

VRC 603: A Phase 1 Dose-Escalation Study of the Safety of AAV8-VRC07 (VRC-HIVAAV070-00-GT) Recombinant AAV Vector Expressing VRC07 HIV-1 Neutralizing Antibody in Antiretroviral-Treated, HIV-1 Infected Adults with Controlled Viremia

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

18-I-0030

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18 Years
Max Age: 65 Years

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

ARV Therapy;
Broadly Neutralizing;
Gene Transfer;
Monoclonal Antibody;
AAV8

Recruitment Keyword(s)

None

Condition(s)

HIV-1 Infected Adults with Controlled Viremia

Investigational Drug(s)

VRC-HIVAAV070-00-GT (AAV8-VRC07)

Investigational Device(s)

None

Intervention(s)

Genetic: VRC-HIVAAV070-00-GT (AAV8-VRC07)

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

The Human Immunodeficiency Virus (HIV) attacks the immune system. Scientists have created a gene that could be transferred to the cells of people with HIV. The gene should tell the cells to make an antibody called VRC07. This antibody fights HIV. The VRC07 gene is packaged into a man-made version of a virus called AAV8.

Objectives:

To see if AAV8-VRC07 is safe. To study if it causes cells to produce the VRC07 antibody.

Eligibility:

Adults ages 18-65 who are HIV infected but in general good health and have been taking the same HIV medicine for at least 3 months

Design:

Participants were screened in a different protocol.

Participants received the study product on day 1. It was injected one or more times in the upper arm or thigh using a needle. Participants weight was measured to calculate the dose.

Women may have had a pregnancy test.

For 7 days after getting the study product, participants checked their temperature with a thermometer. They noted any symptoms in an electronic or paper diary.

Participants will have study visits. At each one, they will have a physical exam and medical history. They will have blood drawn and may have saliva collected.

The study visit schedule is as follows:

For 12 weeks: 1 visit a week

For the next 12 weeks: 1 visit every other week

Then about 1 visit a month

After 1 year in the study: a visit every 6 months for the next 4 years.

Total study participation is 5 years.

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Eligibility

INCLUSION CRITERIA:

A volunteer must have met all of the following criteria:

-Able and willing to complete the informed consent process.

-18 to 65 years of age.

-HIV-1 infected.

-On a stable antiretroviral regimen for greater than or equal to 3 months.

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

-Based on history and examination, must be in general good health with no evidence of clinically significant lab abnormalities and without additional clinically significant medical conditions as per exclusion criteria.

-Willing to maintain or establish a relationship with a primary health care provider for medical management of HIV infection while participating in the study.

-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.

-Laboratory tests assessing individual's health will be conducted within 84 days prior to enrollment and values must meet the following criteria:

a. White blood cell count (WBC) 2,500-12,000/mm^3;

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

c. Platelets = 125,000 400,000/mm^3;

d. Hemoglobin greater than or equal to 10.0 gm/dL;

e. Creatinine less than or equal to 1.25 x upper limit of normal (ULN);

f. Alanine aminotransferase (ALT) less than or equal to 1.1 x ULN;

g. Aspartate aminotransferase (AST) less than or equal to 1.1 x ULN; and,

h. Viral Load (VL) less than or equal to 50 copies/mL and a CD4 count greater than or equal to 300/mcL (microliter).

Male-Specific Criteria:

-Males must agree to use condoms for all sexual activity of any reproductive potential for 52 weeks after receiving the study product.

Female-Specific Criteria:

-If a woman is sexually active with a male partner and has no history of hysterectomy, tubal ligation or menopause, she must agree to use either a prescription birth control method or a barrier birth control method from the time of study enrollment through study Week 52, or to be monogamous with a partner who has had a vasectomy.

-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 volunteer would have been excluded if one or more of the following conditions applied:

-Previous receipt of monoclonal antibody whether licensed or investigational.

-Previous receipt of gene therapy product.

-Ongoing AIDS-related opportunistic infection (including oral thrush).

-Active injection drug use or active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

-A titer of pre-existing antibodies to AAV8 capsid is greater than 1:90.

-Weight > 115 kg for Group 3 participants only.

-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.

-Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.

-Active liver disease such as chronic hepatitis.

-Hypertension that is not well controlled by medication.

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

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

-Current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

-Any other chronic or clinically significant medical 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; OR clinically significant forms of asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.


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Citations:

Lynch RM, Boritz E, Coates EE, DeZure A, Madden P, Costner P, Enama ME, Plummer S, Holman L, Hendel CS, Gordon I, Casazza J, Conan-Cibotti M, Migueles SA, Tressler R, Bailer RT, McDermott A, Narpala S, O'Dell S, Wolf G, Lifson JD, Freemire BA, Gorelick RJ, Pandey JP, Mohan S, Chomont N, Fromentin R, Chun TW, Fauci AS, Schwartz RM, Koup RA, Douek DC, Hu Z, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE; VRC 601 Study Team. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Transl Med. 2015 Dec 23;7(319):319ra206. doi: 10.1126/scitranslmed.aad5752.

Balazs AB, Ouyang Y, Hong CM, Chen J, Nguyen SM, Rao DS, An DS, Baltimore D. Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission. Nat Med. 2014 Mar;20(3):296-300. doi: 10.1038/nm.3471. Epub 2014 Feb 9.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Joseph P. Casazza III, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)



Laura Novik, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 12S251
10 Center Drive
Bethesda, Maryland 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:

NCT03374202

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NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

VRC 603: A Phase 1 Dose-Escalation Study of the Safety of AAV8-VRC07 (VRC-HIVAAV070-00-GT) Recombinant AAV Vector Expressing VRC07 HIV-1 Neutralizing Antibody in Antiretroviral-Treated, HIV-1 Infected Adults with Controlled Viremia

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

18-I-0030

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18 Years
Max Age: 65 Years

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

ARV Therapy;
Broadly Neutralizing;
Gene Transfer;
Monoclonal Antibody;
AAV8

Recruitment Keyword(s)

None

Condition(s)

HIV-1 Infected Adults with Controlled Viremia

Investigational Drug(s)

VRC-HIVAAV070-00-GT (AAV8-VRC07)

Investigational Device(s)

None

Intervention(s)

Genetic: VRC-HIVAAV070-00-GT (AAV8-VRC07)

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

The Human Immunodeficiency Virus (HIV) attacks the immune system. Scientists have created a gene that could be transferred to the cells of people with HIV. The gene should tell the cells to make an antibody called VRC07. This antibody fights HIV. The VRC07 gene is packaged into a man-made version of a virus called AAV8.

Objectives:

To see if AAV8-VRC07 is safe. To study if it causes cells to produce the VRC07 antibody.

Eligibility:

Adults ages 18-65 who are HIV infected but in general good health and have been taking the same HIV medicine for at least 3 months

Design:

Participants were screened in a different protocol.

Participants received the study product on day 1. It was injected one or more times in the upper arm or thigh using a needle. Participants weight was measured to calculate the dose.

Women may have had a pregnancy test.

For 7 days after getting the study product, participants checked their temperature with a thermometer. They noted any symptoms in an electronic or paper diary.

Participants will have study visits. At each one, they will have a physical exam and medical history. They will have blood drawn and may have saliva collected.

The study visit schedule is as follows:

For 12 weeks: 1 visit a week

For the next 12 weeks: 1 visit every other week

Then about 1 visit a month

After 1 year in the study: a visit every 6 months for the next 4 years.

Total study participation is 5 years.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

A volunteer must have met all of the following criteria:

-Able and willing to complete the informed consent process.

-18 to 65 years of age.

-HIV-1 infected.

-On a stable antiretroviral regimen for greater than or equal to 3 months.

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

-Based on history and examination, must be in general good health with no evidence of clinically significant lab abnormalities and without additional clinically significant medical conditions as per exclusion criteria.

-Willing to maintain or establish a relationship with a primary health care provider for medical management of HIV infection while participating in the study.

-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.

-Laboratory tests assessing individual's health will be conducted within 84 days prior to enrollment and values must meet the following criteria:

a. White blood cell count (WBC) 2,500-12,000/mm^3;

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

c. Platelets = 125,000 400,000/mm^3;

d. Hemoglobin greater than or equal to 10.0 gm/dL;

e. Creatinine less than or equal to 1.25 x upper limit of normal (ULN);

f. Alanine aminotransferase (ALT) less than or equal to 1.1 x ULN;

g. Aspartate aminotransferase (AST) less than or equal to 1.1 x ULN; and,

h. Viral Load (VL) less than or equal to 50 copies/mL and a CD4 count greater than or equal to 300/mcL (microliter).

Male-Specific Criteria:

-Males must agree to use condoms for all sexual activity of any reproductive potential for 52 weeks after receiving the study product.

Female-Specific Criteria:

-If a woman is sexually active with a male partner and has no history of hysterectomy, tubal ligation or menopause, she must agree to use either a prescription birth control method or a barrier birth control method from the time of study enrollment through study Week 52, or to be monogamous with a partner who has had a vasectomy.

-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 volunteer would have been excluded if one or more of the following conditions applied:

-Previous receipt of monoclonal antibody whether licensed or investigational.

-Previous receipt of gene therapy product.

-Ongoing AIDS-related opportunistic infection (including oral thrush).

-Active injection drug use or active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

-A titer of pre-existing antibodies to AAV8 capsid is greater than 1:90.

-Weight > 115 kg for Group 3 participants only.

-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.

-Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.

-Active liver disease such as chronic hepatitis.

-Hypertension that is not well controlled by medication.

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

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

-Current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

-Any other chronic or clinically significant medical 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; OR clinically significant forms of asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.


--Back to Top--

Citations:

Lynch RM, Boritz E, Coates EE, DeZure A, Madden P, Costner P, Enama ME, Plummer S, Holman L, Hendel CS, Gordon I, Casazza J, Conan-Cibotti M, Migueles SA, Tressler R, Bailer RT, McDermott A, Narpala S, O'Dell S, Wolf G, Lifson JD, Freemire BA, Gorelick RJ, Pandey JP, Mohan S, Chomont N, Fromentin R, Chun TW, Fauci AS, Schwartz RM, Koup RA, Douek DC, Hu Z, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE; VRC 601 Study Team. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Transl Med. 2015 Dec 23;7(319):319ra206. doi: 10.1126/scitranslmed.aad5752.

Balazs AB, Ouyang Y, Hong CM, Chen J, Nguyen SM, Rao DS, An DS, Baltimore D. Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission. Nat Med. 2014 Mar;20(3):296-300. doi: 10.1038/nm.3471. Epub 2014 Feb 9.

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Joseph P. Casazza III, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)



Laura Novik, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 12S251
10 Center Drive
Bethesda, Maryland 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:

NCT03374202

--Back to Top--