Safety and Immunogenicity of a Tetravalent Dengue Vaccine in HIV-Positive Adults

NCT02741128 | Completed Phase 2 Results DMC

• 2 other identifiers: CYD50U1111-1174-4398
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 4

Brief Summary

The aim of the study was to evaluate the safety and immunogenicity of the Dengue vaccine in a population of special interest, such as HIV-positive adults previously exposed to dengue. Primary Objective:

• To describe the safety of each injection of CYD dengue vaccine in HIV-positive adults previously exposed to dengue. Secondary Objectives:
• To describe the humoral immune response to each dengue serotype at baseline and after each injection of CYD dengue vaccine in HIV-positive adults previously exposed to dengue.
• To detect the CYD dengue vaccinal viremia post-Inj 1 in HIV-positive adults previously exposed to dengue.
• To describe changes in CD4 count and HIV RNA viral load after each injection of CYD dengue vaccine in HIV-positive adults previously exposed to dengue. Observational Objective:
• To describe the FV (YF, Dengue, Zika) serological status in the study population at baseline.

Conditions

Dengue Fever; Dengue Hemorrhagic Fever; Human Immunodeficiency Virus

Keywords

Dengue Fever; Dengue Hemorrhagic Fever; Human Immunodeficiency Virus; CYD Dengue Vaccine

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Unsolicited Systemic Adverse Event (AE)

  An AE was any untoward medical occurrence in a participant administered study vaccine and which did not necessarily have a causal relationship. An unsolicited AE was an observed AE that did not fulfill the conditions pre-listed in the protocol and case report form (CRF) in terms of diagnosis and/or onset window post-vaccination.

  Within 30 minutes after each injection

• Percentage of Participants With Solicited Injection-Site Reactions

  An AE was any untoward medical occurrence in a participant administered study vaccine and which did not necessarily have a causal relationship. A solicited reaction was an expected adverse reaction (AR) observed and reported under the conditions pre-listed in the protocol and CRF and included pain, erythema, and swelling. Injection site reaction was an AR at and around the injection site. Injection site reactions were commonly inflammatory reactions.

  Up to 7 days after each injection

• Percentage of Participants With Solicited Systemic Reactions

  A solicited reaction was an "expected" adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. Solicited systemic reactions included headache, fever, localized or topical manifestations that were not associated with the vaccination or administration site.

  Up to 14 days after each injection

• Percentage of Participants With Unsolicited AE, Serious and Non-Serious AEs of Special Interest (AESIs)

  An unsolicited AE was an observed AE that did not fulfill the conditions pre-listed in the protocol and CRF in terms of diagnosis and/or onset window post-vaccination. An AESI was one of scientific and medical concern specific to the study vaccine, for which ongoing monitoring, and rapid communication by the Investigator to the Sponsor was appropriate. The following were considered as serious AESI: serious hypersensitivity/allergic reactions occurring in all participants within 7 days after vaccination; serious viscerotropic disease occurring in all participants within 30 days after vaccination; serious neurotropic disease occurring in all participants within 30 days after vaccination; serious dengue disease requiring hospitalization occurring in all participants at any time during the study. The following were considered as non-serious AESIs, hypersensitivity/allergic reactions occurring in all participants within 7 days after vaccination.

  Up to 28 days after each injection

• Percentage of Participants With Serious AEs (SAEs) and Hospitalized Virologically-Confirmed Dengue (VCD) Cases

  An AE was any untoward medical occurrence in a participant administered study vaccine and which does not necessarily have a causal relationship. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Hospitalized VCD cases were defined as an acute febrile illness with diagnosis of dengue requiring hospitalization. The confirmatory dengue diagnosis was performed through virological detection.

  From the date of randomization until 6-month safety follow-up (approximately 38 months)

Secondary Outcomes (4)

• Geometric Mean Titers of Neutralizing Antibody Levels Against Each of the 4 Parental Dengue Virus Strains

  Baseline (Day 0) and 28 days after each injection

• Percentage of Participants With a Detected and Quantified CYD Dengue Vaccinal Viremia

  At 7 and 14 days post-injection 1

• Percentage of Participants With Clusters of Differentiation 4 (CD4) Count Decrease

  From Day 28 to Day 393 (28 days after each injection)

• Percentage of Participants With Confirmed Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Viral Load Increase

  From Day 28 to Day 393 (28 days after each injection)

Study Arms (2)

CYD Dengue vaccine group

EXPERIMENTAL

Subjects will receive 3 doses of CYD dengue vaccine at 0, 6, and 12 months

Biological: CYD Dengue Vaccine

Placebo vaccine group

PLACEBO COMPARATOR

Subjects will receive 3 doses of placebo (NaCl, 0.9%) vaccine at 0, 6, and 12 months

Biological: Placebo (NaCl 0.9%) vaccine group

Interventions

CYD Dengue Vaccine BIOLOGICAL

0.5 mL, Subcutaneous at Day 0, 6 and 12 months, respectively

CYD Dengue vaccine group

Placebo (NaCl 0.9%) vaccine group BIOLOGICAL

0.5 mL, Subcutaneous at Day 0, 6 and 12 months, respectively

Placebo vaccine group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 to 50 years on the day of first study vaccination (study product administration) ("18 to 50" means from the day of the 18th birthday to the day before the 51th birthday)
• Inform concent form has been signed and dated
• Able to attend all scheduled visits and to comply with all trial procedures
• Documented seropositivity for HIV-1 infection based on the Brazilian HIV Guidelines' laboratory criteria (i.e., two positive results obtained from different and independent determination methods) or detectable HIV-1 viral load results in the past
• Stable HIV condition according to Brazilian HIV Guidelines (i.e., with both CD4 count \> 350 cells/mm3 and sustainable and undetectable HIV viral load \[\< 50 copies/mL\]) for at least 1 year before consent
• Stable antiretroviral (ART) regimen based on local HIV protocol for at least 1 year before consent.
• Previous exposure to dengue confirmed by rapid diagnostic test (RDT) or dengue IgG ELISA

You may not qualify if:

• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination)
• Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination or planned receipt of any vaccine in the 4 weeks following any trial vaccination
• Previous vaccination against dengue disease with either the trial vaccine or another vaccine
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Self-reported or suspected congenital or acquired immunodeficiency, except HIV; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Previous acquired immunodeficiency syndrome (AIDS), defined as the occurrence of opportunistic infection in the last 2 years before consent
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol abuse or drug addiction
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
• Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C) on the day of vaccination. A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
• Previous CD4 count \< 200 cells/mm3 (nadir) since diagnosis of HIV
• History of chronic and active hepatitis B infection or HBsAg-positive

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (4)

Investigational Site Number :0760002

Nova Iguaçu, Rio de Janeiro, 26030-380, Brazil

Location

Investigational Site Number :0760004

Natal, Rio Grande do Norte, 59025050, Brazil

Location

Investigational Site Number :0760001

São Paulo, 04040-002, Brazil

Location

Investigational Site Number :0760003

São Paulo, 04121-000, Brazil

Location

MeSH Terms

Conditions

Dengue; Severe Dengue; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2016
• First Posted: April 18, 2016
• Study Start: November 6, 2019
• Primary Completion: January 19, 2023
• Study Completion: January 19, 2023
• Last Updated: July 19, 2024
• Results First Posted: July 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

BR (4)