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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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02315703
First Posted: December 12, 2014
Last Update Posted: November 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
  Purpose
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.

Condition Intervention Phase
Healthy Biological: Ad26.Mos.HIV Biological: MVA-Mosaic Biological: gp140 DP Low-dose Biological: gp140 DP High-dose Drug: Placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Crucell Holland BV:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 393
Actual Study Start Date: December 22, 2014
Estimated Study Completion Date: July 18, 2022
Primary Completion Date: May 2, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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.
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.
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: 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.
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.
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.
Drug: Placebo
Normal saline, 0.5 mL injection administered intramuscularly.
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.
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 High-dose
The gp140 DP vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly.
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.
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.
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.
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.
Drug: Placebo
Normal saline, 0.5 mL injection administered intramuscularly.
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.
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: 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.
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.
Drug: Placebo
Normal saline, 0.5 mL injection administered intramuscularly.

Detailed Description:
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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
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): NCT02315703


Locations
United States, Colorado
Aurora, Colorado, United States
United States, Florida
Miami, Florida, United States
United States, Maryland
Rockville, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Texas
Austin, Texas, United States
Rwanda
Kigali, Rwanda
South Africa
Cape Town, South Africa
Durban, South Africa
Johannesburg, South Africa
Thailand
Bangkok, Thailand
Uganda
Entebbe, Uganda
Kampala, Uganda
Sponsors and Collaborators
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
Investigators
Study Director: Crucell Holland BV Clinical Trials Crucell Holland BV
  More Information

Responsible Party: Crucell Holland BV
ClinicalTrials.gov Identifier: NCT02315703     History of Changes
Other Study ID Numbers: CR106152
HIV-V-A004 ( Other Identifier: Crucell Holland BV )
IPCAVD009 ( Other Identifier: Crucell Holland BV )
First Submitted: December 9, 2014
First Posted: December 12, 2014
Last Update Posted: November 7, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Crucell Holland BV:
Healthy
Acquired Immuno-Deficiency Syndrome
Acquired Immunodeficiency Syndrome Virus
adenovirus serotype 26
Ad26.Mos.HIV
Modified Vaccinia Ankara
Glycoprotein
Adjuvant
Vaccine
Placebo

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Vaccines
Krestin
Aluminum phosphate
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antibiotics, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Interferon Inducers
Radiation-Protective Agents
Protective Agents
Antacids
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents