Clinical Trial of HIV Vaccine Combinations in Healthy Men and Women

NCT ID: NCT03408262

Last Updated: 2024-10-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-06

Study Completion Date

2020-02-10

Brief Summary

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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

Detailed Description

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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.

Conditions

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Human Immunodeficiency Virus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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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

Group Type ACTIVE_COMPARATOR

CN54gp140/MPLA

Intervention Type BIOLOGICAL

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

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

Group Type EXPERIMENTAL

Ad4-EnvCN54

Intervention Type BIOLOGICAL

Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

CN54gp140/MPLA

Intervention Type BIOLOGICAL

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

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

Group Type EXPERIMENTAL

Ad4-EnvCN54

Intervention Type BIOLOGICAL

Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

CN54gp140/MPLA

Intervention Type BIOLOGICAL

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

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

Group Type EXPERIMENTAL

Ad4-EnvCN54

Intervention Type BIOLOGICAL

Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

CN54gp140/MPLA

Intervention Type BIOLOGICAL

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

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

Group Type ACTIVE_COMPARATOR

MVA-CN54

Intervention Type BIOLOGICAL

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

CN54gp140/MPLA

Intervention Type BIOLOGICAL

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

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

Group Type EXPERIMENTAL

Ad4-EnvCN54

Intervention Type BIOLOGICAL

Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

MVA-CN54

Intervention Type BIOLOGICAL

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

CN54gp140/MPLA

Intervention Type BIOLOGICAL

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

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

Group Type EXPERIMENTAL

Ad4-EnvCN54

Intervention Type BIOLOGICAL

Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

MVA-CN54

Intervention Type BIOLOGICAL

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

CN54gp140/MPLA

Intervention Type BIOLOGICAL

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

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

Group Type EXPERIMENTAL

Ad4-EnvCN54

Intervention Type BIOLOGICAL

Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

MVA-CN54

Intervention Type BIOLOGICAL

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

CN54gp140/MPLA

Intervention Type BIOLOGICAL

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

Interventions

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Ad4-EnvCN54

Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54

Intervention Type BIOLOGICAL

MVA-CN54

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

Intervention Type BIOLOGICAL

CN54gp140/MPLA

Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant

Intervention Type BIOLOGICAL

Other Intervention Names

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CN54-M

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Imperial College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Lewis, MD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

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NIHR Imperial Clinical Research Facility

London, , United Kingdom

Site Status

Countries

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United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Ad4HIV

Identifier Type: -

Identifier Source: org_study_id

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