An Experimental Medicine Multicenter Trial to Evaluate the Safety and Immunogenicity of Experimental Versus Authorized SARS-CoV-2 Vaccine Candidates as a Booster Dose in Healthy Participants Previously Vaccinated With Authorized mRNA SARS-CoV-2 Vaccines.

Обзор

The SOLVE-01 trial is a study evaluating four SARS-CoV-2 vaccines as booster injections: two experimental vaccines (CD40.RBDv and CD40.Pan.CoV, both combined with the Hiltonol® adjuvant) and two authorised vaccines (Comirnaty® and NuvaxovidTM). This trial is designed for healthy adults aged 18 to 65 at the time of signing the informed consent form. The main objectives of this trial are: * to evaluate the safety of the two experimental vaccines, * to determine the antibody response induced by the vaccines and its durability. Participants will: * Receive one injection of vaccine and two intradermal skin tests * Come to the hospital 10 visits for medical exams and blood and saliva sample collection * Keep a diary of their symptoms and the treatments taken

Вмешательства

• Биопрепарат CD40.RBDv vaccine adjuvanted with Hiltonol®
  used at the dose of 1.0 mg subcutaneously Poly-ICLC adjuvant (Hiltonol) used at a dose of 1.0 mg and will be mixed with CD40.RBDv vaccine just prior to subcutaneous injection at day 0.
• Биопрепарат CD40.Pan.CoV vaccine adjuvanted with Hiltonol®
  used at the dose of 1.0 mg subcutaneously Poly-ICLC adjuvant (Hiltonol) used at a dose of 1.0 mg and will be mixed with CD40.Pan.CoV vaccine just prior to subcutaneous injection at day 0.
• Биопрепарат Comirnaty® vaccine
  administered intramuscularly at day 0. The version of the Comirnaty® vaccine and the dose will be the one adapted to the variant circulating at the start of trial and authorised by EMA.
• Биопрепарат Nuvaxovid™ vaccine
  administered intramuscularly at day 0. The version of the Nuvaxovid™ vaccine and the dose will be the one commercialised at the start of trial and authorised by EMA.

Первичные конечные точки

• Safety_Proportion of participants without any grade 3 or 4 adverse event [Срок оценки: Between Day 0 and Week 4]
• Immunogenicity_Geometric mean titers of neutralizing antibodies [Срок оценки: At Week 4 and Week 48]

Вторичные конечные точки (12)

• Safety_Number of Solicited local and systemic Adverse Reactions [Срок оценки: up to Day 7 (7 days post vaccination) for local ARs and Week 2 (14 days post vaccination) for systemic ARs]
• Safety_Number of Unsolicited adverse events [Срок оценки: from Day 0 to end of trial]
• Safety_Number of Serious Adverse Events [Срок оценки: from Day 0 to end of the trial]
• Immunogenicity_humoral immune response (IgG binding) [Срок оценки: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48]
• Immunogenicity_humoral immune response (IgG binding) [Срок оценки: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48]
• Immunogenicity_persistence of immune imprinting [Срок оценки: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48]
• Immunogenicity_humoral immune response (neutralizing antibody titers) [Срок оценки: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48]
• Immunogenicity_humoral immune response (neutralizing antibody titers) [Срок оценки: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48]
• Immunogenicity_specific antibody responses [Срок оценки: between Day 0 and Week 48]
• Immunogenicity_T-cell immunogenicity (polyfunctional cross reactive specific T-cells) [Срок оценки: at Day 0 (before vaccination), Week 4, Week 12, Week 24, Week 36 and Week 48]
• Immunogenicity_T-cell immunogenicity (polyfunctional cross reactive specific T-cells) [Срок оценки: at Day 0 (before vaccination), Week 4, Week 12, Week 24, Week 36 and Week 48]
• Immunogenicity_durability of T-cell immune responses (polyfunctional cross reactive specific T-cells) [Срок оценки: at Day 0 (before vaccination), Week 24 and Week 48]

Критерии участия

Критерии включения

• Male and female subjects aged 18 to 65 years inclusive at the time of the screening visit
• Having received at least two doses of COVID-19 mRNA vaccines in the past with the last dose received more than 6 months prior to IMP administration in the trial
• In healthy condition or with stable health status which is defined as an existing disease that has not required a significant change in treatment or hospitalization for worsening before enrolment, and for which neither a significant change in treatment or hospitalization for worsening is expected in the near future.
• For woman of childbearing potential: a negative Beta-HCG blood test measure during the screening visit, and a negative highly sensitive pregnancy urinary test the day of the vaccination visit

• if heterosexually active female, consistently using a highly effective method of contraception with partner from at least 21 days prior to enrolment through 4 months after the IMP administration. Highly effective contraception is defined as using any of the following methods:

• Combined hormonal contraception with inhibition of ovulation (estrogen and progesterone containing);
• Intrauterine device (IUD);
• Intrauterine hormone releasing system (IUS);
• Hormonal contraception (progesterone only);
• Successful vasectomy in the male partner (considered successful if a participant reports that a male partner has (i) documentation of azoospermia by microscopy, or (ii) a vasectomy more than 2 years ago with no resultant pregnancy despite unprotected sexual activity post vasectomy);
• Or not be of reproductive potential, such as having reached menopause (no menses for 1 year without an alternative medical cause) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation.
• Agree not to seek pregnancy including through alternative methods, such as artificial insemination or in vitro fertilization until 4 months after the IMP administration.
• Participant who was born male, if heterosexually active male, using an effective method of contraception with their partner from the IMP administration until 4 months thereafter. All male participants also agree not to donate sperm during this period.
• Negative nasopharyngeal antigenic test for SARS-CoV-2 on the day of screening and before randomisation
• Participant who has normal biological values:

• Hemoglobin ≥ 11.0 g/dL for participants who were born female, ≥ 13.0 g/dL for participants who were born male;
• White blood cell count = 3,300 to 12,000 cells/mm3;
• Total lymphocyte count ≥ 800 cells/mm3;
• Platelets = 125,000 to 550,000/mm3;
• ALT, AST, and alkaline phosphatase < 1.25 times the institutional upper limit of normal;
• Creatinine <1.1x institutional upper limit of normal of the laboratory;
• Normal urine test: absence of glucose, protein and haemoglobin
• Negative HIV antigen/antibody test;
• Negative Hepatitis B surface antigen (HBsAg);
• Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive;
• Willingness to undertake SARS-CoV-2 testing according to study protocol, and receive SARS-CoV-2 test results
• Willingness and availability to be followed for the planned duration of the study in one of the dedicated trial centres
• Informed and signed written consent form before performance of any trial-related screening procedures
• Agree to be registered in the French Health Ministry computerised file (for France only)
• Being covered by Health Insurance (for France only)

Критерии исключения

• Acute febrile infection (body temperature ≥ 38.0°C) within the previous 72 hours and/or presenting symptoms suggestive of COVID-19 or SARS-CoV-2 infection within the previous 28 days or having been in contact with an infected individual for the last 14 days before the inclusion visit
• Any medical condition that could impair the immune response: clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

• A process that would affect the immune response;
• A process that would require medication that affects the immune response;
• Any contraindication to repeated injections or blood draws;
• A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being during the study period;
• A condition or process for which signs or symptoms could be confused with reactions to vaccine, or
• Any condition specifically listed among the exclusion criteria below.
• Pregnancy or breastfeeding that is currently ongoing, or positive pregnancy test at screening visit and the day of the vaccination
• Immunodeficiency
• Asthma: a condition that requires active medical intervention or monitoring to avert grave danger to asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a participant who:

• Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or
• Uses moderate/high dose inhaled corticosteroids, or
• In the past year has either of the following: (i) Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids or (ii) Needed emergency care, urgent care, hospitalization, or intubation for asthma.
• Diabetes type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes).
• Thyroidectomy, or thyroid disease requiring medication during the last 12 months
• Hypertension:

• If a person has been diagnosed with hypertension, exclude for blood pressure that is not well controlled (well-controlled blood pressure is defined as consistently ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic). For these participants, blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrolment;
• If a person has NOT been diagnosed with hypertension, exclude for systolic blood pressure ≥ 150 mm Hg at enrolment or diastolic blood pressure ≥ 100 mm Hg at enrolment. (the measurement must be performed on a person who has been lying down for at least 5 minutes and repeat at the end of the consultation, if appropriated). Tension must be confirmed outside the clinical site to rule out hypertension.
• Contraindication to the IMPs including hypersensitivity
• BMI ≥ 40 kg/m2; ≤ 18 kg/m2; or BMI ≥ 35 kg/m2 with 2 or more of the following: age > 45, systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known hyperlipidemia
• Bleeding disorder diagnosed (e.g., coagulation factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
• Malignancy (Not excluded: volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study)
• Asplenia: any condition resulting in the absence of a functional spleen
• Seizure disorder: History of seizure(s) within past three years. Also excluded if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
• History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including arrhythmia requiring medication, treatment, or clinical follow-up)
• History of autoimmune disease
• Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with or serve as a contraindication to protocol adherence, assessment of safety, or a volunteer's ability to give informed consent
• Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
• History of serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a volunteer who had a non-anaphylactic adverse reaction to pertussis vaccine as a child)
• Investigational research agents received within 30 days before IMP administration
• Experimental vaccine(s) received within the last 5 years in a prior vaccine trial
• Live attenuated vaccines (e.g., measles, mumps, and rubella (MMR); oral polio vaccine (OPV); varicella; yellow fever) received within 30 days before IMP administration or scheduled within 28 days after the injection scheduled within the protocol
• Vaccines that are not live attenuated vaccines and were received within 21 days prior to IMP administration (e.g., tetanus, pneumococcal, Hepatitis A or B)
• Blood-derived products or immunoglobulin received within 6 months before IMP administration\*
• Current anti-tuberculosis (TB) prophylaxis or therapy received within 3 months before IMP administration \*
• Allergy treatment with antigen injections within 30 days before IMP administration or that are scheduled within 14 days after IMP administration\*
• Immunosuppressive medications or immunomodulators (such as cytokines or interferons) received within last three months before IMP administration. (Not excluded: (1) corticosteroid nasal spray; \[2\] topical corticosteroids for mild, uncomplicated dermatitis; or (2) a single course of oral/parenteral corticosteroids at doses < 2 mg/kg/day and length of therapy < 11 days with completion at least 30 days prior to enrolment) or low dose oral corticosteroids (≤10 mg prednisone/day) or corticosteroids for the treatment of immune-related adverse events\*
• Other prohibited medications: Corticosteroids > 10 mg prednisone equivalent/day (not excluded: topical preparations) \*
• Person participating in another research involving the human person or participating in another research involving the human person with an exclusion period still in progress at screening
• Intent to participate in another study of an investigational research agent during the planned duration of the study
• Participants who are not able to understand and to follow all required study procedures for the whole period of the study in the judgment of the investigator
• Under tutorship (only for France), guardianship, or deprived of liberty by a juridical or administrative decision
• Planned absence that could affect participation in the study (travel abroad, relocation, impending professional mutation...)

• The scheduled use of these treatments up to 6 months after the injection also represents a contraindication

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 2 центра

• Hôpital Henri Mondor — Créteil
• CIC 1417 - Hôpital Cochin — Paris

Швейцария · 1 центр

• Centre Hospitalier Universitaire Vaudois (CHUV) — Lausanne

Идентификаторы

NCT: NCT07605520 · ANRS0711s SOLVE-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗