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Clinical Trial of HIV Vaccine Combinations in Healthy Men and Women (Ad4HIV)

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ClinicalTrials.gov Identifier: NCT03408262
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Brief Summary:

This is a randomised two-part Phase I study which will explore the impact of different boosting options (MVA-CN54 and recombinant CN54gp140 protein) for oral Adenovirus serotype 4 vector prime expressing HIV-1 CN54 envelope (Ad4-EnvCN54) designed to optimize systemic and mucosal antibody responses.

Part 1 is exploratory and designed to select conditions capable of promoting enhanced systemic and mucosal B cell responses in a limited number of participants. Part 2 is dependent upon Part 1 and is designed to study groups selected on performance in part 1 in an expanded number of subjects. Data from both stages will be combined for safety and immunological analyses.


Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Biological: Ad4-EnvCN54 Biological: MVA-CN54 Biological: CN54gp140/MPLA Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: A Phase I Single-Blind Randomised Trial Investigating Immunisation Strategies Using Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA Combinations in Order to Maximise Antibody Responses to Human Immunodeficiency Virus
Actual Study Start Date : October 6, 2017
Estimated Primary Completion Date : December 20, 2018
Estimated Study Completion Date : December 20, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Group A
Month 0: oral placebo Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo
Biological: CN54gp140/MPLA
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
Other Name: CN54-M

Experimental: Group B
Month 0: Ad4-EnvCN54 Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo
Biological: Ad4-EnvCN54
Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: CN54gp140/MPLA
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
Other Name: CN54-M

Experimental: Group C
Month 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo
Biological: Ad4-EnvCN54
Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: CN54gp140/MPLA
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
Other Name: CN54-M

Experimental: Group D
Month 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo Month 6: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo
Biological: Ad4-EnvCN54
Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: CN54gp140/MPLA
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
Other Name: CN54-M

Active Comparator: Group E
Month 0: oral placebo Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54
Biological: MVA-CN54
Live, non-replicating modified vaccinia Ankara vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: CN54gp140/MPLA
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
Other Name: CN54-M

Experimental: Group F
Month 0: Ad4-EnvCN54 Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54
Biological: Ad4-EnvCN54
Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: MVA-CN54
Live, non-replicating modified vaccinia Ankara vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: CN54gp140/MPLA
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
Other Name: CN54-M

Experimental: Group G
Month 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54
Biological: Ad4-EnvCN54
Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: MVA-CN54
Live, non-replicating modified vaccinia Ankara vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: CN54gp140/MPLA
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
Other Name: CN54-M

Experimental: Group H
Month 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54
Biological: Ad4-EnvCN54
Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: MVA-CN54
Live, non-replicating modified vaccinia Ankara vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Biological: CN54gp140/MPLA
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
Other Name: CN54-M




Primary Outcome Measures :
  1. Mucosal antigen-specific antibodies measured by binding ELISA [ Time Frame: At two weeks after the final immunisation ]
    Frequency of mucosal binding antibodies to HIV CN54gp140 antigen

  2. Adverse events [ Time Frame: Up to twenty-four weeks after the final immunisation ]
    Frequency of adverse events


Secondary Outcome Measures :
  1. Serum and mucosal antigen-specific antibodies measured by binding ELISA [ Time Frame: Up to twenty-four weeks after the final immunisation ]
    Frequency of serum and mucosal binding antibodies to HIV CN54gp140 antigen



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Men and women aged between 18 and 50 years on the day of screening
  2. BMI between 18-30
  3. Seronegative for Adenovirus 4 serum neutralising antibodies
  4. Available for follow-up for the duration of the study
  5. Willing and able to give written informed consent
  6. At low risk of HIV infection and willing to remain so for the duration of the study defined as:

    • no history of injecting drug use in the previous ten years
    • no gonorrhoea or syphilis in the last six months
    • no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months
    • no unprotected anal or vaginal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative
  7. Willing to undergo HIV testing
  8. Willing to undergo a STI screen for chlamydia, gonorrhoea and syphilis
  9. Must agree to require male sexual partner to use condoms, from at least 14 days before the first vaccination until at least 4 months after the last
  10. If heterosexually active female capable of becoming pregnant, must (in addition to requiring male partner to use condoms) agree to use hormonal contraception, or to complete abstinence, from at least 30 days before the first vaccination until at least 4 months after the last. [Note: Acceptable hormonal contraception is combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation. Complete abstinence can be used, when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, lactational amenorrhoea method, and IUD/IUS are not acceptable methods of contraception.]
  11. If sexually active male, must agree to use condoms from the day of first vaccination until at least 4 months after the last. [Note: Additional use of an effective method of contraception is recommended for any non-pregnant female partner over the same period.]
  12. Agree to abstain from donating blood, eggs or sperm from the day of first vaccination until at least 3 months after the end of their participation in the trial
  13. Registered with a GP for at least the past month
  14. Entered and clearance obtained from The Overvolunteering Prevention System (TOPS) database

Exclusion Criteria:

  1. Are pregnant or breast feeding, or living with anyone under the age of 5 years old or over 75 years old
  2. Have close contact with an immunocompromised individual thought to be at clinical risk from Adenovirus infection
  3. Clinically relevant abnormality on history or examination including:

    1. Liver disease with inadequate hepatic function
    2. Any skin condition which may interfere with the trial assessment of the injection sites
    3. Haematological, metabolic, gastrointestinal or cardio-pulmonary disorders
    4. Uncontrolled infection; autoimmune disease, immunodeficiency
  4. Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
  5. History of severe local or general reaction to vaccination defined as

    • Local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the arm, not resolving within 72 hours
    • General: fever ≥39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
  6. Receipt of live attenuated vaccine within 60 days or other vaccine within 30 days of enrolment
  7. Receipt of an experimental vaccines containing HIV antigens, Ad4 and MVA-C products at any time in the past
  8. Receipt of blood products or immunoglobin within 4 months of screening, or drugs that suppress the immune system, such as steroids (including inhaled steroids, excluding topical steroids unless applied to the upper arm), in the preceding 3 months
  9. Participating in another trial of a medicinal product, completed less than 30 days prior to enrolment
  10. HIV 1 or 2 positive or indeterminate on screening
  11. Positive for antibodies to hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment
  12. Clinically significant positive reaction in antinuclear antibody screen or clinically significant immunoglobulin (IgA, IgG or IgM) values
  13. Grade 1 or above clinically significant routine laboratory parameters
  14. Unable to read and/or speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent
  15. Women with a history of toxic shock syndrome
  16. Women using an intrauterine device for contraception (as incompatible with softcup sampling)
  17. Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
  18. Unlikely to comply with protocol

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): NCT03408262


Contacts
Contact: Tom Cole, PhD 02033136198 t.cole@imperial.ac.uk
Contact: David Lewis, MD 02033136195 d.lewis@imperial.ac.uk

Locations
United Kingdom
NIHR Imperial Clinical Research Facility Recruiting
London, United Kingdom, W12 0HS
Contact: Allan Listanco       allan.listanco@nhs.net   
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: David Lewis, MD Imperial College London

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT03408262     History of Changes
Other Study ID Numbers: Ad4HIV
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: January 23, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases