Evaluating the Safety and Immunogenicity of EnvSeq-1 and CH505 M5 gp120 Envs Adjuvanted With GLA-SE in Healthy, HIV-Uninfected Adults

A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of EnvSeq-1 and CH505 M5 gp120 Envs Adjuvanted With GLA-SE in Healthy, HIV-Uninfected Adult Participants

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of EnvSeq-1 and CH505 M5 gp120 Envs adjuvanted with GLA-SE in healthy, HIV-uninfected adults.

This study will evaluate the safety, tolerability, and immunogenicity of EnvSeq-1 and CH505 M5 gp120 Envs adjuvanted with GLA-SE in healthy, HIV-uninfected adults. The three individual EnvSeq-1 HIV vaccine Envs used in this study are called CH505TF gp120, CH505w53 gp120, and CH505w78 gp120.

This study will take place in two parts: Part A and Part B. Participants in Part A will be randomly assigned to one of four groups. Participants in each group will receive CH505TF (admixed with GLA-SE) or placebo by intramuscular (IM) injection at Months 0, 2, 4, 8, and 12.

Study researchers will evaluate participant data from Part A of the study prior to enrolling participants into Part B of the study. Researchers will also evaluate data from Part A to determine the dosing for Part B.

Participants in Part B will be randomly assigned to one of four groups. Participants in each group will receive IM injections at Months 0, 2, 4, 8. GLA-SE will be admixed with all the CH505 gp120 vaccines. Part B, Group 5 will follow a sequential approach to EnvSeq-1 vaccine administration with administration of the CH505TF vaccine at Month 0, then CH505w53 at Month 2, and CH505w78 at Months 4, and 8. Part B, Group 6 participants will follow an additive approach to EnvSeq-1 administration with administration of the CH505TF vaccine at Month 0; then the CH505TF and CH505w53 vaccines at Month 2; then the CH505TF, CH505w53 and CH505w78 vaccines at Month 4; then the CH505w53 and CH505w78 vaccines at Month 8. Part B, Group 7 participants will receive CH505 M5 at Months 0, 2, 4, and 8. Part B, Group 8 participants will receive placebo injections at each time point.

Additional study visits will occur through Month 18 for participants in Part A and through Month 14 for participants in Part B. Visits may include physical examinations and clinical assessments; blood, urine, and stool collection; HIV testing; risk reduction counseling; and interviews/questionnaires. Study staff will contact participants for follow-up health monitoring at Month 24 for participants in Part A and at Month 20 for participants in Part B.

Part C will be an open-label study arm using the EnvSeq-1 proteins in sequential administration (CH505TF, CH505w53, and CH505w78 gp120s) at the same dose as in Part B (400 mcg) to allow for in-depth analysis of B cell precursor frequency.

Inclusion Criteria:

General and Demographic Criteria:

• Age of 18 through 50 years
• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: volunteer demonstrates understanding of this study, completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent before the last required protocol clinic visit
• Willing to be contacted by phone, text message, or e-mail 6 months after completion of the scheduled clinic visits
• Good general health as shown by medical history, physical exam, and screening laboratory tests

HIV-Related Criteria:

• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit.

Laboratory Inclusion Values:

Hemogram/Complete Blood Count (CBC):

• Hemoglobin greater than or equal to 11.5 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
• White blood cell count equal to 3,300 to 12,000 cells/mm^3
• Total lymphocyte count greater than or equal to 800 cells/mm^3
• Remaining differential either within institutional normal range or with site physician approval
• Platelets equal to 125,000 to 550,000/mm^3

Chemistry:

• Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal; creatinine less than or equal to institutional upper limit of normal.

Virology:

• Negative HIV-1 and -2 blood test: Volunteers must have a negative Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).
• Negative Hepatitis B surface antigen (HBsAg)
• Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive

Urine:

• Normal urine:

  • Negative urine glucose, and
  • Negative or trace urine protein, and
  • Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range).

Reproductive Status:

• Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (beta-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.

• Reproductive status: A volunteer who was born female must:

  • Agree to consistently use effective contraception (see the protocol for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using the following methods:
  • Condoms (male or female) with or without a spermicide,
  • Diaphragm or cervical cap with spermicide,
  • Intrauterine device (IUD),
  • Hormonal contraception, or
  • Any other contraceptive method approved by the HVTN 115 Protocol Safety Review Team (PSRT)
  • Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy);
  • Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;
  • Or be sexually abstinent.

• Volunteers who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

Exclusion Criteria:

General:

• Blood products received within 120 days before first vaccination
• Investigational research agents received within 30 days before first vaccination
• Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known hyperlipidemia
• Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 115 study
• Pregnant or breastfeeding
• Active duty and reserve U.S. military personnel

Vaccines and Other Injections:

• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 115 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 115 PSRT will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA or by the national regulatory authority where the volunteer is enrolling. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 115 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 115 PSRT on a case-by-case basis.
• Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine)
• Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, Hepatitis A or B)
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination

Immune System:

• Immunosuppressive medications received within 168 days before first vaccination. (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral prednisone or equivalent at doses less than 60 mg/kg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment.)

• Serious adverse reactions to vaccines or to vaccine components including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)

• Immunoglobulin received within 60 days before first vaccination

• Autoimmune disease, current or history

• Adverse events of special interest (AESIs)

  • Volunteers who currently have, or have a history of, any condition that could be considered an AESI for the products administered in this protocol (representative examples are listed in the study protocol)

• Immunodeficiency

Clinically Significant Medical Conditions:

• Untreated or incompletely treated syphilis infection

• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

  • A process that would affect the immune response,
  • A process that would require medication that affects the immune response,
  • Any contraindication to repeated injections or blood draws,
  • A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,
  • A condition or process for which signs or symptoms could be confused with reactions to vaccine, or
  • Any condition specifically listed among the exclusion criteria below.

• Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent

• Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.

• Current anti-tuberculosis (TB) prophylaxis or therapy

• Asthma exclusion criteria: Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a volunteer who:

  • Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or
  • Uses moderate/high dose inhaled corticosteroids, or
  • In the past year has either of the following:
  • Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;
  • Needed emergency care, urgent care, hospitalization, or intubation for asthma.

• Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)

• Thyroidectomy, or thyroid disease requiring medication during the last 12 months

• Hypertension:

  • If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg diastolic. For these volunteers, blood pressure must be less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment.
  • If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure greater than or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or equal to 100 mm Hg at enrollment.

• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions)

• Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study)

• Seizure disorder: History of seizure(s) within past 3 years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.

• Asplenia: any condition resulting in the absence of a functional spleen

• History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.