Clinical Trial of Quadrivalent Recombinant Norovirus Vaccine (Pichia Pastoris)

NCT04563533 | Completed Phase 1 DMC

• 1 other identifier: LKM-2020-NoV01
• Study Type: interventional
• Target: 580
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the research is to evaluate the safety and tolerability of the tetravalent recombinant Norovirus vaccine at different doses, to initially explore the immunogenicity of the vaccine, and to determine the appropriate dose of the product for later clinical trials.This trial adopts the seamless design of phase I/IIa, which is carried out in two phases, phase I and phase IIa, phase I is the age/dose climbing phase, and phase IIa is the dose expansion phase.It is planned to enroll 580 subjects, divided into 5 age groups, including: young adults (18-59 years old, 60 people), adolescents (6 -17 years old, 60 people), and elderly (≥60 years old, 160 people) , Toddlers (2-5 years old, 140), infants (6 weeks to 23 months old, 160).The test vaccine contains recombinant HuNoV GI.1-VP1 protein, HuNoV GII.3-VP1 protein, HuNoV GII.4-VP1 protein, HuNoV GII.17-VP1 protein, and each dose contains 12.5μg/type/0.5ml/bottle (Low dose), 25μg/type/0.5ml/piece (high dose).

Conditions

Acute Gastroenteritis

Keywords

prevention

Outcome Measures

Primary Outcomes (2)

• The number of adverse events after intramuscular injection

  The main observation methods of adverse reactions mainly include laboratory examination, local reactions and systemic reactions at the administration site.

  6 months after full vaccination

• The positive conversion rate of norovirus antibody 30 days after the whole course of vaccination

  For young adults, the elderly, young children, infants and young children, the 4-fold growth rate of norovirus IgA, IgG, and HBGA blocking antibodies and the positive conversion rate after immunity were analyzed 30 days after the full immunization.

  30 days after full immunization

Study Arms (8)

adults of phase I

EXPERIMENTAL

Healthy people aged 18-59

Biological: Low-dose vaccine; Biological: High-dose vaccine; Biological: Placebo (containing aluminum)

teenagers of phase I

EXPERIMENTAL

Healthy people aged 6-17

Biological: Low-dose vaccine; Biological: High-dose vaccine; Biological: Placebo (containing aluminum)

elderly of phase I

PLACEBO COMPARATOR

Healthy people 60 years old and above

Biological: Low-dose vaccine; Biological: High-dose vaccine; Biological: Placebo (containing aluminum); Biological: Placebo (without aluminum)

Toddler of phase I

EXPERIMENTAL

Healthy people aged 2-5

Biological: Low-dose vaccine; Biological: High-dose vaccine; Biological: Placebo (containing aluminum)

Infants of phase I

PLACEBO COMPARATOR

6 weeks old-2 years old healthy person

Biological: Low-dose vaccine; Biological: High-dose vaccine; Biological: Placebo (containing aluminum); Biological: Placebo (without aluminum)

elderly of phase II

EXPERIMENTAL

Healthy people 60 years old and above

Biological: Low-dose vaccine; Biological: High-dose vaccine

Toddler of phase II

PLACEBO COMPARATOR

Healthy people aged 2-5

Biological: Low-dose vaccine; Biological: High-dose vaccine

Infants of phase II

EXPERIMENTAL

6 weeks old-2 years old healthy person

Biological: Low-dose vaccine; Biological: High-dose vaccine

Interventions

Low-dose vaccine BIOLOGICAL

Active ingredients: recombinant ReNoV GI.1-VP1 protein, recombinant ReNoV GII.3-VP1 protein, recombinant ReNoV GII.4-VP1 protein and recombinant ReNoV GII.17-VP1 protein each 12.5μg. Other ingredients: aluminum hydroxide adjuvant 0.25 mg, L-histidine: 1.55 mg, sodium chloride: 4 mg, Tween 80: 1 μg, sodium dihydrogen phosphate: 47 μg, disodium hydrogen phosphate: 87 μg.

Infants of phase I; Infants of phase II; Toddler of phase I; Toddler of phase II; adults of phase I; elderly of phase I; elderly of phase II; teenagers of phase I

High-dose vaccine BIOLOGICAL

Active ingredients: recombinant ReNoV GI.1-VP1 protein, recombinant ReNoV GII.3-VP1 protein, recombinant ReNoV GII.4-VP1 protein and recombinant ReNoV GII.17-VP1 protein each 25μg. Other ingredients: aluminum hydroxide adjuvant 0.25 mg, L-histidine: 1.55 mg, sodium chloride: 4 mg, Tween 80: 2 μg, sodium dihydrogen phosphate: 94 μg, disodium hydrogen phosphate: 173 μg.

Infants of phase I; Infants of phase II; Toddler of phase I; Toddler of phase II; adults of phase I; elderly of phase I; elderly of phase II; teenagers of phase I

Placebo (containing aluminum) BIOLOGICAL

Active ingredients: none Other ingredients: aluminum hydroxide adjuvant: 0.25 mg, L-histidine: 1.55 mg, sodium chloride: 4 mg, Tween 80: 2 μg, sodium dihydrogen phosphate: 94 μg, disodium hydrogen phosphate: 173 μg.

Infants of phase I; Toddler of phase I; adults of phase I; elderly of phase I; teenagers of phase I

Placebo (without aluminum) BIOLOGICAL

Active ingredients: none Other ingredients: L-histidine: 1.55 mg, sodium chloride: 4 mg, Tween 80: 2 μg, sodium dihydrogen phosphate: 94 μg, disodium hydrogen phosphate: 173 μg.

Infants of phase I; elderly of phase I

Eligibility Criteria

• Age: 6 Weeks+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Compliance with this clinical trial observation age is 6 weeks old and above, and can provide legal identification;
• The suspected and/or violating legal guardian has the ability to understand the research procedures and sign an informed consent form;
• Correct and/or prevent the legal guardian who has the ability to read, understand, fill in the diary card/contact card, and promise to participate regularly in accordance with the research requirements;
• The armpit body temperature of all people on the day of entry was \<37.3℃;
• Standards for some groups of people:\<12 months of age: singleton full-term pregnancy (37-42 weeks gestational week) and birth weight 2.5-4.0kg; women of childbearing age: agree to take effective contraceptive measures within 6 months after the first dose is implanted to the full exemption.

You may not qualify if:

• The population laboratory test indicators specified in the plan are abnormal and have clinical significance;
• A history of severe allergies to any component of the test vaccine, including L-histidine, sodium chloride, aluminum hydroxide, such as: anaphylactic shock, allergic laryngeal edema, allergic purpura, thrombocytopenic purpura, local allergies Necrotic reaction (Arthus reaction); or any previous history of severe side effects of vaccines or drugs, such as: allergies, urticaria, skin eczema, dyspnea, angioedema, etc.;
• days before vaccination, suffering from acute disease or in the acute attack of chronic disease (such as asthma, diabetes, thyroid disease, etc.);
• Have taken antipyretic or analgesics within 24 hours before the first dose of vaccination;
• Inoculate the inactivated vaccine within 7 days before the first dose of vaccine, and the live attenuated vaccine within 14 days;
• People suffering from the following diseases:①Suffered from digestive system diseases (such as diarrhea, abdominal pain, vomiting, etc.) in the past 7 days;② Suffer from severe congenital malformations, severe developmental disorders, severe genetic defects, severe malnutrition, etc.;③ Suffering from thrombocytopenia, any coagulation disorders or receiving anticoagulant treatment and other intramuscular injection contraindications;④ Congenital or acquired immunodeficiency, or receive immunosuppressive therapy within 6 months (for example, systemic glucocorticoid prednisone or similar drugs have been used for more than 2 consecutive weeks within 6 months). Local medications (such as ointments, eye drops, inhalants or nasal sprays) should not exceed the recommended dose in the instructions or show any signs of systemic exposure;⑤ Has been diagnosed with infectious diseases, such as tuberculosis, viral hepatitis and/or human immunodeficiency virus (HIV) infection;⑥ Having convulsions, epilepsy, encephalopathy (such as congenital brain hypoplasia, brain trauma, brain tumor, cerebral hemorrhage, cerebral obstruction, infection, chemical drug poisoning, etc. caused brain nerve tissue damage, etc.) and a history of mental illness or family history;⑦ No spleen, functional asthenia, as well as any cause of asthenia or splenectomy;⑧ Suffering from severe cardiovascular disease (pulmonary heart disease, pulmonary edema), severe liver and kidney disease, diabetes with complications;
• Have received blood or blood-related products, including immunoglobulins, within 3 months, or plan to use them during the study period (within 1 month after enrollment and full exemption);
• Any research or unregistered products (drugs, vaccines, biological products or devices) have been used within 3 months before enrollment, or planned to be used during the research period;
• Plan to move or leave the local area for a long time during the research period;
• Any situation that the researcher believes may interfere with the evaluation of the research purpose;
• Standards for certain groups of people:①\<12 months old: IVF, multiple fetuses, currently suffering from perianal abscess, severe eczema, pathological jaundice, parents with HIV infection;② Persons ≥18 years of age: Physical examination before enrollment is hypertension (systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg) or hypotension (systolic blood pressure \<89mmHg) (regardless of medication);③Women of childbearing age: are breast-feeding or pregnant (including a positive urine pregnancy test) or have a pregnancy plan during the study period (in the group to within 6 months after the full exemption).

Sponsors & Collaborators

• Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.: lead

Study Sites (1)

Liuzhou Center for Disease Control and Prevention

Liuchow, Guangxi, 545000, China

Location

MeSH Terms

Interventions

Vaccines

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• teng huang, master

  Deputy Director of Vaccine Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The subjects, investigators, monitors, and data analysts are not aware of treatment allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A single-center, randomized, blinded, multi-cohort, placebo-controlled trial design was adopted.

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 24, 2020
• Study Start: August 5, 2020
• Primary Completion: September 29, 2024
• Study Completion: September 29, 2024
• Last Updated: October 1, 2024

Record last verified: 2024-09

Locations

CN (1)