临床试验方案公布！全世界首例接种新冠病毒疫苗mRNA-1273用于临床试验

2020-5-11 17:27| 编辑: 班木芙兰| 查看: 1953| 评论: 0

摘要: Safety and Immunogenicity Study of2019-nCoVVaccine(mRNA-1273) to Prevent SARS-CoV-2 Infection美国生物技术企业莫德纳公司24日宣布，已向美国国家过敏症和传染病研究所运送了该公司生产的首批新型冠状病毒疫苗m ...

Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) to Prevent SARS-CoV-2 Infection

美国生物技术企业莫德纳公司24日宣布，已向美国国家过敏症和传染病研究所运送了该公司生产的首批新型冠状病毒疫苗mRNA-1273，用于开展一期临床试验。

这家位于美国马萨诸塞州的公司发表声明说，疫苗mRNA-1273是一种抗新型冠状病毒的信使核糖核酸（mRNA）疫苗，可针对病毒的刺突蛋白发挥作用。刺突蛋白是病毒感染宿主细胞的关键所在，也是过去研发严重急性呼吸综合征（SARS）冠状病毒疫苗和中东呼吸综合征（MERS）冠状病毒疫苗时的靶点。

美国《科学》杂志19日在线发表的一篇论文显示，新冠病毒的刺突蛋白结构与SARS冠状病毒的刺突蛋白结构非常相近。

mRNA技术是近年来兴起的新一代疫苗技术，其原理是利用mRNA诱导免疫系统对病原体中的蛋白质作出反应。其优势在于制备步骤简单、开发与生产周期短，对流行病疫情可以较快反应。但目前尚无完成临床试验的成品mRNA疫苗问世。

莫德纳公司说，与美国国家卫生研究院下属的国家过敏症和传染病研究所合作开发了这种疫苗。该批次的疫苗生产由国际组织“流行病防范创新联盟”资助。

Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

Detailed Description:

This is a phase I, open-label, dose ranging clinical trial in males and non-pregnant females, 18 to 55 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of 2019-novel coronavirus (nCoV). Enrollment will occur at one domestic site. Forty-five subjects will be enrolled into one of three cohorts (25 microgram [mcg], 100 mcg, 250 mcg). Subjects will receive an intramuscular (IM) injection (0.5 milliliter [mL]) of mRNA-1273 on Days 1 and 29 in the deltoid muscle and will be followed through 12 months post second vaccination (Day 394). Follow-up visits will occur 1, 2 and 4 weeks post each vaccination (Days 8, 15, 29, 36, 43, and 57), as well as 3, 6 and 12 months post second vaccination (Days 119, 209 and 394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults. The secondary objective is to evaluate the immunogenicity as measured by IgG ELISA to the 2019-nCoV S protein following a 2-dose vaccination schedule of mRNA-1273 at Day 57.

Study Design

Study Type:Interventional (Clinical Trial)EstimatedEnrollment:45 participantsAllocation:Non-RandomizedIntervention Model:Sequential AssignmentMasking:None (Open Label)Primary Purpose:PreventionOfficial Title:Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of2019-nCoVVaccine(mRNA-1273) in Healthy AdultsActualStudy Start Date:March 3, 2020EstimatedPrimary Completion Date:June 1, 2021EstimatedStudy Completion Date:June 1, 2021

Arms and Interventions

ArmIntervention/treatmentExperimental: Arm 1

25 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29. n=15 (4 sentinel, 11 non-sentinel).

Biological: mRNA-1273

Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike protein 2019-nCoV. mRNA-1273 consists of an mRNA Drug Substance that is manufactured into LNPs composed of the proprietary ionizable lipid, SM-102, and 3 commercially available lipids, cholesterol, DSPC, and PEG2000 DMG.

Experimental: Arm 2

100 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29. n=15 (4 sentinel, 11 non-sentinel).

Biological: mRNA-1273

Experimental: Arm 3

250 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29. n=15 (4 sentinel, 11 non-sentinel).

Biological: mRNA-1273

Outcome Measures

Primary Outcome Measures :

Frequency of solicited local reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post-vaccination ]
Frequency of any medically-attended adverse events (MAAEs) [ Time Frame: Day 1 to Day 394 ]
Frequency of any new-onset chronic medical conditions (NOCMCs) [ Time Frame: Day 1 to Day 394 ]
Frequency of any serious adverse events (SAEs) [ Time Frame: Day 1 to Day 394 ]
Frequency of any unsolicited adverse events (AEs) [ Time Frame: Through 28 days post-vaccination ]
Frequency of solicited systemic reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post-vaccination ]
Grade of any unsolicited adverse events (AEs) [ Time Frame: Through 28 days post-vaccination ]
Grade of solicited local reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post-vaccination ]
Grade of solicited systemic reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post-vaccination ]

Secondary Outcome Measures :

Geometric mean fold rise (GMFR) in IgG titer from baseline [ Time Frame: Day 1 to Day 57 ]
Geometric mean titer (GMT) of antibody [ Time Frame: Day 57 ]
Percentage of subjects who seroconverted [ Time Frame: Day 1 to Day 57 ]
Seroconversion is defined as a 4-fold change in antibody titer from baseline
Ages Eligible for Study: 18 Years to 55 Years (Adult)Sexes Eligible for Study: AllAccepts Healthy Volunteers: Yes
Inclusion Criteria:

A subject must meet all of the following criteria to be eligible to participate in this study:
Provides written informed consent prior to initiation of any study procedures.
Be able to understand and agrees to comply with planned study procedures and be available for all study visits.
Agrees to the collection of venous blood per protocol.
Male or non-pregnant female, 18 to 55 years of age, inclusive, at time of enrollment.
Body Mass Index 18-35 kg/m^2, inclusive, at screening.
Women of childbearing potential* must agree to use or have practiced true abstinence** or use at least one acceptable primary form of contraception.***, **** Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to subjects in a same sex relationship).
*Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement).
**True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
***Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject's first vaccination, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products.
****Must use at least one acceptable primary form of contraception for at least 30 days prior to the first vaccination and at least one acceptable primary form of contraception for 60 days after the last vaccination.
Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each vaccination.
Male subjects of childbearing potential*: use of condoms to ensure effective contraception with a female partner from first vaccination until 3 months after the last vaccination.
*Biological males who are post-pubertal and considered fertile until permanently sterile by bilateral orchiectomy or vasectomy.
Male subjects agree to refrain from sperm donation from the time of first vaccination until 3 months after the last vaccination.
Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius).
Pulse no greater than 100 beats per minute.
Systolic blood pressure (BP) is 85 to 150 mmHg, inclusive.
Clinical screening laboratory evaluations (white blood cell (WBC), hemoglobin (Hgb), platelets (PLTs), alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), alkaline phosphatase (ALP), total bilirubin (T. Bili), Lipase, prothrombin time (PT), and partial thromboplastin time (PTT)) are within acceptable normal reference ranges at the clinical laboratory being used.
Must agree to have samples stored for secondary research.
Agrees to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

A subject who meets any of the following criteria will be excluded from participation in this study:
Positive pregnancy test either at screening or just prior to each vaccine administration.
Female subject who is breastfeeding or plans to breastfeed from the time of the first vaccination through 60 days after the last vaccination.
Has any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation.*
*Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.
Presence of self-reported or medically documented significant medical or psychiatric condition(s).*
*Significant medical or psychiatric conditions include but are not limited to: Respiratory disease (e.g., chronic obstructive pulmonary disease [COPD], asthma) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years. Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics.
Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease) or history of myocarditis or pericarditis as an adult.
Neurological or neurodevelopmental conditions (e.g., migraines, epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis or transverse myelitis).
Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed.
An autoimmune disease, including hypothyroidism without a defined non-autoimmune cause, localized or history of psoriasis.
An immunodeficiency of any cause.
Has an acute illness*, as determined by the site PI or appropriate sub-investigator, with or without fever [oral temperature >38.0 degrees Celsius (100.4 degrees Fahrenheit)] within 72 hours prior to each vaccination.
*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV types 1 or 2 antibodies at screening.
Has participated in another investigational study involving any investigational product* within 60 days, or 5 half-lives, whichever is longer, before the first vaccine administration.
*study drug, biologic or device
Currently enrolled in or plans to participate in another clinical trial with an investigational agent* that will be received during the study-reporting period.**
*Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication.
**13 months after the first vaccination.
Has previously participated in an investigational study involving lipid nanoparticles (LNPs) (a component of the investigational vaccine assessed in this trial).
Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to any previous licensed or unlicensed vaccines.
Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness.*

Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs during the preceding 6-month period prior to vaccine administration (Day 1). The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.

Received immunoglobulins and/or any blood or blood products within the 4 months before the first vaccine administration or at any time during the study.
Has any blood dyscrasias or significant disorder of coagulation.
Has any chronic liver disease, including fatty liver.
Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 6 months before the first vaccine administration.
Has a positive test result for drugs of abuse at screening or before the first vaccine administration. If cannabis is the only detected drug, inclusion is permitted.
Has any abnormality or permanent body art (e.g., tattoo) that would interfere with the ability to observe local reactions at the injection site (deltoid region).
Received or plans to receive a licensed, live vaccine within 4 weeks before or after each vaccination.
Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or after each vaccination.
Receipt of any other 2019-nCoV or other experimental coronavirus vaccine at any time prior to or during the study.
Known close contact of anyone known to have 2019-nCoV infection within 2 weeks prior to vaccine administration.
Has traveled to China within 30 days before the first vaccination.
Current use of any prescription or over-the-counter medications within 7 days prior to vaccination, unless approved by the investigator.
The subject must agree to refrain from donating blood or plasma during the study.
Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment through 28 days after the second vaccination.

声明：

1、凡本网注明“来源：小桔灯网”的所有作品，均为本网合法拥有版权或有权使用的作品，转载需联系授权。
2、凡本网注明“来源：XXX（非小桔灯网）”的作品，均转载自其它媒体，转载目的在于传递更多信息，并不代表本网赞同其观点和对其真实性负责。其版权归原作者所有，如有侵权请联系删除。
3、所有再转载者需自行获得原作者授权并注明来源。