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

• ClinicalTrials.gov Identifier: NCT02741128
• Recruitment Status: Recruiting
• First Posted: April 18, 2016
• Last Update Posted: March 10, 2020
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

The aim of the study is 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.

Condition or disease	Intervention/treatment	Phase
Dengue Fever; Dengue Hemorrhagic Fever; Human Immunodeficiency Virus	Biological: CYD Dengue Vaccine; Biological: Placebo (NaCl 0.9%) vaccine group	Phase 2

Detailed Description:

Eligible subjects will be randomized in a 2:1 ratio into 1 of 2 groups to receive 3 injections of either CYD dengue vaccine or placebo at 0, 6, and 12 months. The enrollment of subjects will be carried out in two steps, including an early safety data review before the second step. The duration of each subject's participation in the study will be approximately 18 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity of a Tetravalent Dengue Vaccine in HIV-Positive Adults Aged 18 to 50 Years in Brazil
• Actual Study Start Date: November 6, 2019
• Estimated Primary Completion Date: March 2022
• Estimated Study Completion Date: March 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: CYD Dengue vaccine group; Subjects will receive 3 doses of CYD dengue vaccine at 0, 6, and 12 months	Biological: CYD Dengue Vaccine; 0.5 mL, Subcutaneous at Day 0, 6 and 12 months, respectively
Placebo Comparator: Placebo vaccine group; Subjects will receive 3 doses of placebo (NaCl, 0.9%) vaccine at 0, 6, and 12 months	Biological: Placebo (NaCl 0.9%) vaccine group; 0.5 mL, Subcutaneous at Day 0, 6 and 12 months, respectively

Outcome Measures

Primary Outcome Measures :

1. Number of participants reporting unsolicited systematic AE, solicited injection site reactions, solicited systemic reactions, unsolicited AEs, serious and non-serious AEs of special interests, SAE and hospitalized virologically confirmed dengue cases [ Time Frame: Day 0 up to 18 Months post vaccination ]
   Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever (temperature), Headache, Malaise, Myalgia, and Asthenia

Secondary Outcome Measures :

1. Summary of Neutralizing antibody levels against each dengue virus serotype at baseline and 28 days after each injection in each group [ Time Frame: Baseline and 28 days after each injection ]
   Neutralizing antibody levels against each dengue virus serotype will be measured using dengue plaque reduction neutralization test (PRNT).
2. Summary of CYD dengue vaccinal viremia following first vaccination with CYD dengue vaccine or placebo injection [ Time Frame: 7 and 14 days post injection 1 ]
3. Summary of CD4 count after each injection of CYD dengue vaccine [ Time Frame: 28 days after each injection ]
4. Summary of HIV RNA viral load after each injection of CYD dengue vaccine [ Time Frame: 28 days after each injection ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• History of chronic and active hepatitis C infection or HCV Ab-positive
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine > 3 times the upper limit of normal range (ULN)
• Hemoglobin (Hb) < 10 g/dL
• White blood cell count (WBC) < 1500 cells/mm3
• Platelets < 100,000 cells/mm3.

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext 1 then #; Contact-US@sanofi.com

Locations

Brazil

Investigational Site Number 0760002; Recruiting

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

Investigational Site Number 0760001; Recruiting

São Paulo, Brazil, 04040-002

Investigational Site Number 0760003; Recruiting

São Paulo, Brazil, 04121-000

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi Pasteur, a Sanofi Company

More Information

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02741128
• Other Study ID Numbers: CYD50; U1111-1174-4398 ( Other Identifier: WHO )
• First Posted: April 18, 2016
• Last Update Posted: March 10, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

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

Additional relevant MeSH terms:

Dengue; Severe Dengue; Acquired Immunodeficiency Syndrome; HIV Infections; Hemorrhagic Fevers, Viral; Immunologic Deficiency Syndromes; Fever; Immune System Diseases; Body Temperature Changes; Signs and Symptoms; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Slow Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs