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A Safety and Immunogenicity Trial of IHV01 (FLSC-001)

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ClinicalTrials.gov Identifier: NCT02756208
Recruitment Status : Completed
First Posted : April 29, 2016
Last Update Posted : September 6, 2018
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
Profectus BioSciences, Inc.
Information provided by (Responsible Party):
Charles E. Davis, Jr., University of Maryland

Brief Summary:
This study is designed to evaluate the safety of the FLSC vaccine and will be a randomized, placebo-controlled, modified double-blinded dose escalation study in 60 healthy adult volunteers (Human Immunodeficiency Virus-1 uninfected).

Condition or disease Intervention/treatment Phase
HIV Infection Biological: 0.25 mL FLSC Vaccine Group Biological: 0.25 mL Placebo Group Biological: 0.5 mL FLSC Vaccine Group Biological: 0.5 mL Placebo Group Biological: 1.0 mL FLSC Vaccine Group Biological: 1.0 mL Placebo Group Phase 1

Detailed Description:
This is a Phase 1 randomized, placebo-controlled, modified double-blinded dose escalation study in 60 healthy adult volunteers who are Human Immunodeficiency Virus-1 (HIV-1) uninfected. Participants in the study will receive 4 injections at 0, 4, 8 and 24 weeks and will be followed for an additional 24 weeks. The total study duration will be 48 weeks. As this is a Phase 1 trial, the primary objective is to document safety of the Full Length Single Chain (FLSC) gp120-CD4 complex vaccine with a secondary objective to evaluate immune responses induced by the vaccine. This vaccine is being evaluated as it is constructed so that the gp120 and CD4 moieties form a stable intra-chain binding interaction that forms a transition state structure that presents conserved, conformational domains involved in the early HIV replication process. It is hypothesized that antibodies directed to these epitopes would be highly cross-reactive and potentially useful for HIV vaccine development.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase I Safety and Immunogenicity Trial of IHV01 in HIV-1 Uninfected Volunteers
Actual Study Start Date : November 2015
Actual Primary Completion Date : July 2018
Actual Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: 0.25 mL FLSC Vaccine Group ENROLLED
Fifteen volunteers will be vaccinated with 75 mcg (0.25 mL) FLSC on study days 0, 28, 56 and 168.
Biological: 0.25 mL FLSC Vaccine Group
FLSC vaccine 75 mcg (0.25 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
Other Name: Full length single chain gp120-CD4 complex vaccine

Placebo Comparator: 0.25 mL Placebo Group ENROLLED
Five volunteers will be vaccinated with 0.25 mL placebo on study days 0, 28, 56 and 168.
Biological: 0.25 mL Placebo Group
Placebo saline 0.25 mL given by intramuscular injection into the arm on study Days 0, 28, 56, 168
Other Name: sterile saline

Experimental: 0.5 mL FLSC Vaccine Group ENROLLED
Fifteen volunteers will be vaccinated with 150 mcg (0.5 mL) FLSC on study days 0, 28, 56 and 168.
Biological: 0.5 mL FLSC Vaccine Group
FLSC vaccine 150 mcg (0.5 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
Other Name: Full length single chain gp120-CD4 complex vaccine

Placebo Comparator: 0.5 mL Placebo Group ENROLLED
Five volunteers will be vaccinated with 0.5 mL placebo on study days 0, 28, 56 and 168.
Biological: 0.5 mL Placebo Group
Placebo sterile saline 0.5 mL given by intramuscular injection into the arm on study Days 0, 28, 56, 168
Other Name: sterile saline

Experimental: 1.0 mL FLSC Vaccine Group ENROLLED
Fifteen volunteers will be vaccinated with 300 mcg (1.0 mL) FLSC on study days 0, 28, 56 and 168.
Biological: 1.0 mL FLSC Vaccine Group
FLSC vaccine 300 mcg (1.0 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
Other Name: Full length single chain gp120-CD4 complex vaccine

Placebo Comparator: 1.0 mL Placebo Group ENROLLED
Five volunteers will be vaccinated with 1.0 mL placebo on study days 0, 28, 56 and 168.
Biological: 1.0 mL Placebo Group
Placebo sterile saline 1.0 mL given by intramuscular injection into the arm on study Days 0, 28, 56, 168
Other Name: sterile saline




Primary Outcome Measures :
  1. Frequency of severe local and systemic reactogenicity signs and symptoms [ Time Frame: 48 weeks ]
    Signs and symptoms include pain, tenderness, maximum severity of pain and/or tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms

  2. Frequency of Adverse Events [ Time Frame: 48 weeks ]
    Adverse events by body system and dose group. Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products

  3. Measurements of laboratory safety [ Time Frame: 48 weeks ]
    Evaluation of variation in white blood cells (WBC), CD4 lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransaminase(AST) and creatinine at baseline and following vaccinations, by treatment group


Secondary Outcome Measures :
  1. Magnitude of anti-FLSC antibodies [ Time Frame: 2 and 4 weeks after each vaccination and 24 weeks after last vaccination ]
    anti-FLSC antibodies as assessed by ELISA

  2. Magnitude of anti gp-120 (BaL) antibodies [ Time Frame: 2 and 4 weeks after each vaccination and 24 weeks after last vaccination ]
    anti-gp-120 (BaL) antibodies as assessed by ELISA

  3. Magnitude of competitive antibody titers to CD4i epitopes [ Time Frame: 2 and 4 weeks after each vaccination and 24 weeks after last vaccination ]
    competitive antibody titers to CD4i epitopes



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age: 18 to 45 years of age.
  2. Sex: Male or Female (female volunteers of child bearing potential must have a negative serum beta human chorionic gonadotropin (b-HCG or pregnancy) test at time of screening and entry into the study and provide assurance of the use of effective(as judged by the investigator) birth control methods or abstinence beginning at least 60 days prior to the study and during the study
  3. Documented HIV-1 negative by ELISA
  4. Be in good general health without clinically significant medical history, physical examination findings, or clinically significant abnormal laboratory results (i.e., chronic medical conditions as noted in the exclusion criteria such as cancer as well as any conditions that in the opinion of the investigator might pose a risk to the volunteer)
  5. No identifiable risk factor for acquisition of HIV infection (i.e., intravenous drug use/needle sharing, unprotected sex with multiple partners)
  6. Negative b-HCG pregnancy test on the day of initial vaccination.
  7. Negative screen for Hepatitis B surface antigen (HBsAg);
  8. Negative screen for antibodies to Hepatitis C virus (Patient may enroll if patient can provide documentation of negative hepatitis C viral load.)
  9. Participant must have a CD4 count ( a type of white blood cells) within the normal range of the clinical laboratory utilized for the study and a CD4 percentage within 20% of the normal range of the clinical laboratory
  10. Laboratory parameters must be within pre-specified limits as defined by exclusion criteria.
  11. Volunteers must be willing and able to provide written informed consent to participate in the study.
  12. Available for at least 48 weeks of follow-up.

Exclusion Criteria:

  1. High risk behavior for acquisition of HIV within 24 weeks of study entry(i.e., intravenous drug use/needle sharing, unprotected sex with multiple partners)
  2. Volunteers with an acute and clinically significant medical event (as determined by the investigator) within the past 30 days of screening.
  3. Have active tuberculosis or other systemic infectious process by review of systems and physical examination
  4. Have a history of immunodeficiency, autoimmune disease, or use of immunosuppressive medications
  5. Current treatment for malignancy other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  6. Is pregnant
  7. History of any chronic illness that would interfere with conduct or completion of study(as determined by the investigator)
  8. Have evidence of psychiatric, medical and/or substance abuse problems during the past 24 weeks that the investigator believes would adversely affect the volunteer's ability to participate in the trial
  9. Have occupational or other responsibilities that would prevent completion of participation in the study
  10. Have received any live, attenuated vaccine except rabies vaccine within 60 days of study entry
  11. Vaccine (FDA approved; e.g. influenza, pneumovax, etc) administration within 30 days of immunization with the study vaccine. NOTE: Medically indicated subunit or killed vaccines (e.g., Hepatitis A or Hepatitis B) should be given prior to trial initiation or after completion of the study immunizations. If patient requires immunization, injections should be given more than 2 weeks prior or 2 weeks after study immunization
  12. Have used experimental therapeutic agents within 30 days of study entry
  13. Have received blood products or immunoglobulins in the past 12 weeks
  14. Have a history of anaphylaxis or other serious adverse reactions to vaccines
  15. Have previously received an HIV vaccine
  16. Volunteers with any of the following laboratory parameters at the screening visit (within 30 days of immunization): Hemoglobin <10 (without having received a blood or red blood cell transfusion within 30 days prior to laboratory test); neutrophil count <750 cells/mm3; platelet count <50,000/mm3; serum creatinine > 2.0 mg/dL; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limits of normal; total bilirubin > 1.5 mg/dL
  17. Pregnant women or women who are breast-feeding; female volunteers of childbearing potential who are not using or willing to use an effective (as judged by the investigator) barrier contraceptive methods or abstinence while enrolled in this study.
  18. Use of any immune modulators or suppressors within 45 days of study entry including but not limited to agents such as interleukins (e.g. IL-2), interferons (e.g. IFN-*), high dose systemic steroids (e.g. ≥ 20 mg prednisone equivalent/day) for > 30 days, thalidomide, filgrastim (G-CSF), sargramostim (GM-CSF), dinitrochlorobenzene (DNCB), thymosin alpha, thymopentin, inosiplex, polyribonucleoside, ditiocarb sodium, cyclosporin, mycophenolate mofetil, methotrexate, and cancer chemotherapy.
  19. No other investigational agent within 30 days of study entry
  20. Any other condition which, in the opinion of the investigator, might interfere with completion of the study or evaluation of the results
  21. Have active Hepatitis B virus infection (positive HBsAg) or Hepatitis C infection(defined as positive antibodies)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02756208


Locations
United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Bill and Melinda Gates Foundation
Profectus BioSciences, Inc.
Investigators
Principal Investigator: Charles E Davis, M.D. Institute of Human Virology

Responsible Party: Charles E. Davis, Jr., Associate Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT02756208     History of Changes
Other Study ID Numbers: HP-00065547
First Posted: April 29, 2016    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Charles E. Davis, Jr., University of Maryland:
vaccine
healthy volunteer

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs