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Safety, Tolerability, and Immunogenicity Study of Homologous Ad26 Mosaic Vector Vaccine Regimens or Heterologous Ad26 Mosaic and MVA Mosaic Vector Vaccine Regimens With Glycoprotein 140 (gp140) for Human Immunodeficiency Virus (HIV) Prevention

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ClinicalTrials.gov Identifier: NCT02315703
Recruitment Status : Active, not recruiting
First Posted : December 12, 2014
Last Update Posted : November 7, 2017
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
US Military HIV Research Program
Beth Israel Deaconess Medical Center
International AIDS Vaccine Initiative
Information provided by (Responsible Party):
Crucell Holland BV

December 9, 2014
December 12, 2014
November 7, 2017
December 22, 2014
May 2, 2016   (Final data collection date for primary outcome measure)
  • Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Week 96 ]
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
  • Number of Participants With Local and Systemic Reactogenicity for 8 Days After First Vaccination [ Time Frame: Up to 8 days after first vaccination at Baseline (Week 0) ]
    Participants will be asked to note occurrences of local reactions: erythema, induration, swelling, pain/tenderness, itching, or warmth at the injection site, and systemic events: daily temperature, fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, rashes, and general itching daily for 8 days post-vaccination. These occurrences will be recorded through the memory aid provided to serve as a reminder to the participants for the next clinic visit.
  • Number of Participants With Local and Systemic Reactogenicity for 8 Days After Second Vaccination [ Time Frame: Up to 8 days after second vaccination at Week 12 ]
    Participants will be asked to note occurrences of local reactions: erythema, induration, swelling, pain/tenderness, itching, or warmth at the injection site, and systemic events: daily temperature, fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, rashes, and general itching daily for 8 days post-vaccination. These occurrences will be recorded through the memory aid provided to serve as a reminder to the participants for the next clinic visit.
  • Number of Participants With Local and Systemic Reactogenicity for 8 Days After Third Vaccination [ Time Frame: Up to 8 days after third vaccination at Week 24 ]
    Participants will be asked to note occurrences of local reactions: erythema, induration, swelling, pain/tenderness, itching, or warmth at the injection site, and systemic events: daily temperature, fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, rashes, and general itching daily for 8 days post-vaccination. These occurrences will be recorded through the memory aid provided to serve as a reminder to the participants for the next clinic visit.
  • Number of Participants With Local and Systemic Reactogenicity for 8 Days After Fourth Vaccination [ Time Frame: Up to 8 days after fourth vaccination at Week 48 ]
    Participants will be asked to note occurrences of local reactions: erythema, induration, swelling, pain/tenderness, itching, or warmth at the injection site, and systemic events: daily temperature, fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, rashes, and general itching daily for 8 days post-vaccination. These occurrences will be recorded through the memory aid provided to serve as a reminder to the participants for the next clinic visit.
  • Envelop (Env) Binding Antibody Titer at Week 28 [ Time Frame: Week 28 ]
    The Env Clade A, B, and C-specific binding antibody titer will be assessed using enzyme-linked immunosorbent assay (ELISA).
Same as current
Complete list of historical versions of study NCT02315703 on ClinicalTrials.gov Archive Site
  • Envelop (Env) Binding Antibody Titer at Week 52 [ Time Frame: Week 52 ]
    The Env Clade A, B, and C-specific binding antibody titer will be assessed using ELISA.
  • Human Immunodeficiency Virus Neutralizing Antibody (HIV nAb) Titer at Week 28 and 52 [ Time Frame: Week 28 and 52 ]
    The Clade A, B, and C-specific HIV nAb titers will be assessed.
  • Glycoprotein 120 (gp120) Binding Antibody Titer at Week 28 and 52 [ Time Frame: Week 28 and 52 ]
    The Clade A, B, and C-specific gp120 binding antibody titers will be assessed using ELISA.
  • Functional Antibody Titer at Week 28 and 52 [ Time Frame: Week 28 and 52 ]
    Functional antibodies titer (percent phagocytosis) will be assessed by antibody-dependent cellular phagocytosis (ADCP) assay.
  • Isotyping Envelop (Env) Binding Antibody Titer at Week 28 and 52 [ Time Frame: Week 28 and 52 ]
    The Isotyping (Clade C) (IgA, IgG1, IgG2, IgG3)- Env binding antibody titers will be assessed using ELISA.
  • Number of Positive Epitopes [ Time Frame: Baseline, Week 26, 28, 50, and 52 ]
    Assays of peptide pool sets covering the Gag, Env or Pol will be evaluated by standard enzyme-linked immunospot assay (ELISPOT) with mapping of positive pools to determine the number of positive epitopes.
Same as current
Not Provided
Not Provided
 
Safety, Tolerability, and Immunogenicity Study of Homologous Ad26 Mosaic Vector Vaccine Regimens or Heterologous Ad26 Mosaic and MVA Mosaic Vector Vaccine Regimens With Glycoprotein 140 (gp140) for Human Immunodeficiency Virus (HIV) Prevention
A Phase 1/2a Trial to Evaluate the Safety/Tolerability and Immunogenicity of Homologous Ad26 Mosaic Vector Regimens or Ad26 Mosaic and MVA Mosaic Heterologous Vector Regimens, With High-Dose, Low-Dose or no Clade C gp140 Protein Plus Adjuvant for HIV Prevention
The purpose of this study is to assess the safety and tolerability of various regimens containing adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV), Modified Vaccinia Ankara (MVA)-Mosaic, and/or HIV type 1 Clade C glycoprotein 140 drug product (gp140 DP) components and to compare envelope binding antibody responses between the different vaccine regimens.
This is a multicenter (more than 1 hospital or medical school team work on a study), randomized (the study drug is assigned by chance), parallel group (each group of participants will be treated at the same time), placebo-controlled (study in which the experimental treatment or procedure is compared to a pretend treatment with no drug in it to test if the drug has a real effect), and double-blind (neither physician nor participant knows the treatment that the participant receives) study. All eligible participants will be randomly assigned to receive 1 of the 8 vaccine regimens. Participants will receive study vaccines (Ad26.Mos.HIV, MVA-Mosaic, gp140 DP, and placebo) 4 times as per assigned regimen. The study comprises a Screening Period (up to 4 weeks), a Vaccination Period (participants will be vaccinated at Baseline (Week 0), Week 12, Week 24 and Week 48), and a Follow-up Period (up to 48 weeks). A long-term follow-up period (approximately 2 years after Week 96) will continue for participants randomized to the regimen subsequently selected for future studies, based on analysis of Week 28 data. If Week 28 data are inconclusive, Week 52 data will be considered for regimen selection. If no clear decision can be made, the extended follow-up period could include participants from more than 1 group for assessing durability of immune responses. Participants' safety will be monitored throughout the study.
Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Healthy
  • Biological: Ad26.Mos.HIV
    Recombinant replication-deficient Ad26 vectored vaccine and consists of 3 Ad26 vectors, one containing a mosaic insert of envelop (Env) sequence, and 2 vectors containing mosaic inserts of Gag and Pol sequences (Ad26.Mos.1.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol). Total dose is 5*10^10 viral particle per 0.5 milliliter (mL) injection administered intramuscularly.
  • Biological: MVA-Mosaic
    Recombinant live attenuated MVA virus-vectored vaccine that has been genetically engineered to express 2 mosaic Gag, Pol, and Env sequences (Mosaic 1 and Mosaic 2). Total dose is 10^8 plaque-forming unit per 0.5 mL injection administered intramuscularly.
  • Biological: gp140 DP Low-dose
    The gp140 DP vaccine containing 50 mcg of total protein, mixed with aluminum phosphate adjuvant (0.425 mg aluminum), per 0.5 mL injection administered intramuscularly.
  • Biological: gp140 DP High-dose
    The gp140 DP vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
  • Drug: Placebo
    Normal saline, 0.5 mL injection administered intramuscularly.
  • Experimental: Group 1
    Participants will receive adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV) vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + HIV type 1 Clade C glycoprotein 140 drug product (gp140 DP) vaccine containing 250 microgram (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48.
    Interventions:
    • Biological: Ad26.Mos.HIV
    • Biological: gp140 DP High-dose
  • Experimental: Group 2
    Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + gp140 DP vaccine containing 50 mcg of total protein mixed with adjuvant at Week 24 and 48.
    Interventions:
    • Biological: Ad26.Mos.HIV
    • Biological: gp140 DP Low-dose
  • Experimental: Group 3
    Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + placebo injection at Week 24 and 48.
    Interventions:
    • Biological: Ad26.Mos.HIV
    • Drug: Placebo
  • Experimental: Group 4
    Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by modified Vaccinia Ankara (MVA)-Mosaic vaccine + gp140 DP vaccine containing 250 mcg of total protein mixed with adjuvant at Week 24 and 48.
    Interventions:
    • Biological: Ad26.Mos.HIV
    • Biological: MVA-Mosaic
    • Biological: gp140 DP High-dose
  • Experimental: Group 5
    Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + gp140 DP vaccine containing 50 mcg of total protein mixed with adjuvant at Week 24 and 48.
    Interventions:
    • Biological: Ad26.Mos.HIV
    • Biological: MVA-Mosaic
    • Biological: gp140 DP Low-dose
  • Experimental: Group 6
    Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + placebo injection at Week 24 and 48.
    Interventions:
    • Biological: Ad26.Mos.HIV
    • Biological: MVA-Mosaic
    • Drug: Placebo
  • Experimental: Group 7
    Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by gp140 DP vaccine containing 250 mcg of total protein mixed with adjuvant + placebo injection at Week 24 and 48.
    Interventions:
    • Biological: Ad26.Mos.HIV
    • Biological: gp140 DP High-dose
    • Drug: Placebo
  • Placebo Comparator: Group 8
    Participants will receive 1 placebo injection at Week 0 and 12; followed by 2 placebo injections at Week 24 and 48.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
393
400
July 18, 2022
May 2, 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participant must be healthy on the basis of physical examination, medical history, electrocardiogram (ECG) and laboratory criteria, and vital signs measurement performed at Screening
  • Participants are negative for human immunodeficiency virus (HIV) infection at Screening
  • All female participants of childbearing potential must have a negative serum (beta human chorionic gonadotropin) at Screening, and a negative urine pregnancy test pre-dose on Week 0, 12, 24, and 48
  • A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction until 3 months after receiving the last dose of study vaccine. A man must agree not to donate sperm until 3 months after receiving the last dose of study vaccine
  • Participants are assessed by the clinic staff as being at low risk for HIV infection

Exclusion Criteria:

  • Participant has chronic active hepatitis B or active hepatitis C, active syphilis infection, chlamydia, gonorrhea, or trichomonas. Active syphilis documented by exam or serology unless positive serology is due to past treated infection
  • In the 12 months prior to enrollment, participant has a history of newly acquired herpes simplex virus type 2 (HSV-2), syphilis, gonorrhea, non-gonococcal urethritis, chlamydia, pelvic inflammatory disease, trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranulomavenereum, chancroid, or hepatitis B
  • Participant has any clinically significant acute or chronic medical condition that in the opinion of the investigator would preclude participation (for example, history of seizure disorders, bleeding/clotting disorder, autoimmune disease, active malignancy, poorly controlled asthma, active tuberculosis or other systemic infections)
  • Participant has had major surgery within the 4 weeks prior to study entry or planned major surgery through the course of the study
  • Participant has had a thyroidectomy, or thyroid disease requiring medication during the last 12 months
  • Participant has a history of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow up)
  • Participant has an ECG (per examination and interpretation of a cardiologist) with clinically significant findings, or features that would interfere with the assessment of myo/pericarditis, including any of the following: a) conduction disturbance (complete left or complete right bundle branch block or nonspecific intraventricular conduction disturbance with QRS >=120 millisecond [ms], PR interval >=220 ms, any 2nd or 3rd degree AV block, or QTc prolongation [>450 ms]); b) significant repolarization (ST segment or T wave) abnormality; c) significant atrial or ventricular arrhythmia, frequent atrial or ventricular ectopy (for example frequent premature atrial contractions, 2 premature ventricular contractions in a row); d) ST elevation consistent with ischemia, or evidence of past or evolving myocardial infarction
  • Participant has a history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products, or neomycin or streptomycin or egg products
Sexes Eligible for Study: All
18 Years to 50 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
Rwanda,   South Africa,   Thailand,   Uganda,   United States
 
 
NCT02315703
CR106152
HIV-V-A004 ( Other Identifier: Crucell Holland BV )
IPCAVD009 ( Other Identifier: Crucell Holland BV )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Crucell Holland BV
Crucell Holland BV
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • US Military HIV Research Program
  • Beth Israel Deaconess Medical Center
  • International AIDS Vaccine Initiative
Study Director: Crucell Holland BV Clinical Trials Crucell Holland BV
Crucell Holland BV
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP