Clinical Trial of HIV Vaccine Combinations in Healthy Men and Women

NCT03408262 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Ad4HIV
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Mucosal Binding IgG Antibodies to HIV CN54gp140 Antigen

  Number of participants with mucosal (semen, nasal, vaginal or rectal) binding IgG antibodies to HIV CN54gp140 antigen, as determined by ELISA

  At two weeks after the final immunisation

• Number of Participants With Severe or Greater (Grades 3-4) Adverse Reactions During the Study

  Number of Participants With Severe or Greater (Grades 3-4) Adverse Reactions up to twenty-four weeks after the final immunisation

  Up to twenty-four weeks after the final immunisation

• Median Concentration of CN54-gp140 Specific IgG Binding Antibodies

  Median concentration of CN54-gp140 specific IgG binding antibodies, as measured by ELISA. Concentration is in ng/mL

  At two weeks after the final immunisation

Secondary Outcomes (1)

• Number of Participants With Detectable Serum Binding Antibodies to HIV CN54gp140 Antigen

  At two weeks post-final immunisation

Study Arms (8)

Group A

ACTIVE COMPARATOR

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

Group B

EXPERIMENTAL

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; Biological: CN54gp140/MPLA

Group C

EXPERIMENTAL

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; Biological: CN54gp140/MPLA

Group D

EXPERIMENTAL

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; Biological: CN54gp140/MPLA

Group E

ACTIVE COMPARATOR

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; Biological: CN54gp140/MPLA

Group F

EXPERIMENTAL

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; Biological: MVA-CN54; Biological: CN54gp140/MPLA

Group G

EXPERIMENTAL

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; Biological: MVA-CN54; Biological: CN54gp140/MPLA

Group H

EXPERIMENTAL

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; Biological: MVA-CN54; Biological: CN54gp140/MPLA

Interventions

Ad4-EnvCN54 BIOLOGICAL

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

Group B; Group C; Group D; Group F; Group G; Group H

MVA-CN54 BIOLOGICAL

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

Group E; Group F; Group G; Group H

CN54gp140/MPLA BIOLOGICAL

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

Also known as: CN54-M

Group A; Group B; Group C; Group D; Group E; Group F; Group G; Group H

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women aged between 18 and 50 years on the day of screening
• BMI between 18-30
• Seronegative for Adenovirus 4 serum neutralising antibodies
• Available for follow-up for the duration of the study
• Willing and able to give written informed consent
• 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
• Willing to undergo HIV testing
• Willing to undergo a STI screen for chlamydia, gonorrhoea and syphilis
• 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
• 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. \[Note: Acceptable hormonal contraception is combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation. Complete abstinence can be used, when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, lactational amenorrhoea method, and IUD/IUS are not acceptable methods of contraception.\]
• If sexually active male, must agree to use condoms from the day of first vaccination until at least 4 months after the last. \[Note: Additional use of an effective method of contraception is recommended for any non-pregnant female partner over the same period.\]

You may not qualify if:

• Are pregnant or breast feeding, or living with anyone under the age of 5 years old or over 75 years old
• Have close contact with an immunocompromised individual thought to be at clinical risk from Adenovirus infection
• Clinically relevant abnormality on history or examination including:
• Liver disease with inadequate hepatic function
• Any skin condition which may interfere with the trial assessment of the injection sites
• Haematological, metabolic, gastrointestinal or cardio-pulmonary disorders
• Uncontrolled infection; autoimmune disease, immunodeficiency
• Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
• 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
• Receipt of live attenuated vaccine within 60 days or other vaccine within 30 days of enrolment
• Receipt of an experimental vaccines containing HIV antigens, Ad4 and MVA-C products at any time in the past
• 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
• Participating in another trial of a medicinal product, completed less than 30 days prior to enrolment

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

NIHR Imperial Clinical Research Facility

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Research Integrity Officer
• Organization: Imperial College London

rgit@imperial.ac.uk

020 7594 1872

Study Officials

• David Lewis, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 23, 2018
• Study Start: October 6, 2017
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: October 16, 2024
• Results First Posted: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)