A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Immune Responses of an Investigational Monovalent Chimpanzee Adenoviral-Vectored Marburg Virus Vaccine in Healthy Adults

开始日期2023-09-25

申办/合作机构

Albert B. Sabin Vaccine Institute, Inc.

[+1]

NCT04723602 / Completed临床1期IIT

Phase 1b Trial to Evaluate Safety, Tolerability and Immune Responses of 2 Monovalent Chimpanzee Adenoviral Vectored Filovirus (Ebola-S and Marburg) Vaccines to Healthy Adults, Collection of Plasma/Serum for the Purposes of Assay Development

Primary Objective:
• To evaluate the safety and tolerability of cAd3-EBO-S and cAd3 Marburg vaccines when administered Intramuscular (IM) at a dose of 1 x 10^11 particle units (PU) to healthy adults.
Secondary Objectives:
To evaluate the antibody response to Monovalent Chimpanzee Adenoviral Vectored Filovirus Ebola-S (cAd3-EBO-S) and Monovalent Chimpanzee Adenoviral Vectored Filovirus (Marburg) (cAd3 Marburg) vaccines as assessed by antigen glycoprotein (GP) specific (enzyme-linked immunosorbent assay) ELISA
To collect sufficient post-vaccination plasma to support further development of filovirus assays

开始日期2021-01-06

申办/合作机构

Albert B. Sabin Vaccine Institute, Inc.

[+2]

NCT03475056 / Completed临床1期IIT

RV 507: A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of the Marburg Chimpanzee Adenovirus Vector Vaccine, VRC-MARADC087-00-VP (cAd3-Marburg), in Healthy Adults

RV 507 was a Phase I, open-label study to examine the safety, tolerability and immunogenicity of an investigational Marburg vaccine given by intramuscular (IM) injection to healthy adults. The study was a dose escalation of VRC-MARADC087-00-VP, a chimpanzee adenovirus serotype 3 (cAd3) vector vaccine, which encodes wild type (WT) glycoprotein (GP) from Marburgvirus.

开始日期2018-10-09

申办/合作机构

National Institute of Allergy & Infectious Diseases

100 项与 VRC-MARADC087-00-VP 相关的临床结果

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100 项与 VRC-MARADC087-00-VP 相关的专利（医药）

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项与 VRC-MARADC087-00-VP 相关的文献（医药）

2023-08-03·The Lancet. Infectious diseases

Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial.

Article

作者: Betty Mwesigwa ; Katherine V Houser ; Amelia R Hofstetter ; Ana M Ortega-Villa ; Prossy Naluyima ; Francis Kiweewa ; Immaculate Nakabuye ; Galina V Yamshchikov ; Charla Andrews ; Mark O'Callahan ; Larisa Strom ; Steven Schech ; Leigh Anne Eller ; Erica L Sondergaard ; Paul T Scott ; Mihret F Amare ; Kayvon Modjarrad ; Amir Wamala ; Allan Tindikahwa ; Ezra Musingye ; Jauhara Nanyondo ; Martin R Gaudinski ; Ingelise J Gordon ; LaSonji A Holman ; Jamie G Saunders ; Pamela J M Costner ; Floreliz H Mendoza ; Myra Happe ; Patricia Morgan ; Sarah H Plummer ; Somia P Hickman ; Sandra Vazquez ; Tamar Murray ; Jamilet Cordon ; Caitlyn N M Dulan ; Ruth Hunegnaw ; Manjula Basappa ; Marcelino Padilla ; Suprabhath R Gajjala ; Phillip A Swanson ; Bob C Lin ; Emily E Coates ; Jason G Gall ; Adrian B McDermott ; Richard A Koup ; John R Mascola ; Aurélie Ploquin ; Nancy J Sullivan ; Hannah Kibuuka ; Julie A Ake ; Julie E Ledgerwood ; RV 508 Study Team

BACKGROUND:

Sudan Ebola virus can cause severe viral disease, with an average case fatality rate of 54%. A recent outbreak of Sudan Ebola virus in Uganda caused 55 deaths among 164 confirmed cases in the second half of 2022. Although vaccines and therapeutics specific for Zaire Ebola virus have been approved for use during outbreak situations, Sudan Ebola virus is an antigenically distinct virus with no approved vaccines available.

METHODS:

In this phase 1, open-label, dose-escalation trial we evaluated the safety, tolerability, and immunogenicity of a monovalent chimpanzee adenovirus 3 vaccine against Sudan Ebola virus (cAd3-EBO S) at Makerere University Walter Reed Project in Kampala, Uganda. Study participants were recruited from the Kampala metropolitan area using International Review Board-approved written and electronic media explaining the trial intervention. Healthy adults without previous receipt of Ebola, Marburg, or cAd3 vectored-vaccines were enrolled to receive cAd3-EBO S at either 1 × 10¹⁰ or 1 × 10¹¹ particle units (PU) in a single intramuscular vaccination and were followed up for 48 weeks. Primary safety and tolerability endpoints were assessed in all vaccine recipients by reactogenicity for the first 7 days, adverse events for the first 28 days, and serious adverse events throughout the study. Secondary immunogenicity endpoints included evaluation of binding antibody and T-cell responses against the Sudan Ebola virus glycoprotein, and neutralising antibody responses against the cAd3 vector at 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT04041570, and is completed.

FINDINGS:

40 healthy adults were enrolled between July 22 and Oct 1, 2019, with 20 receiving 1 × 10¹⁰ PU and 20 receiving 1 × 10¹¹ PU of cAd3-EBO S. 38 (95%) participants completed all follow-up visits. The cAd3-EBO S vaccine was well tolerated with no severe adverse events. The most common reactogenicity symptoms were pain or tenderness at the injection site (34 [85%] of 40), fatigue (29 [73%] of 40), and headache (26 [65%] of 40), and were mild to moderate in severity. Positive responses for glycoprotein-specific binding antibodies were induced by 2 weeks in 31 (78%) participants, increased to 34 (85%) participants by 4 weeks, and persisted to 48 weeks in 31 (82%) participants. Most participants developed glycoprotein-specific T-cell responses (20 [59%, 95% CI 41-75] of 34; six participants were removed from the T cell analysis after failing quality control parameters) by 4 weeks after vaccination, and neutralising titres against the cAd3 vector were also increased from baseline (90% inhibitory concentration of 47, 95% CI 30-73) to 4 weeks after vaccination (196, 125-308).

INTERPRETATION:

The cAd3-EBO S vaccine was safe at both doses, rapidly inducing immune responses in most participants after a single injection. The rapid onset and durability of the vaccine-induced antibodies make this vaccine a strong candidate for emergency deployment in Sudan Ebola virus outbreaks.

FUNDING:

National Institutes of Health via interagency agreement with Walter Reed Army Institute of Research.

2023-01-28·Lancet (London, England)

Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial.

Article

作者: Melinda J Hamer ; Katherine V Houser ; Amelia R Hofstetter ; Ana M Ortega-Villa ; Christine Lee ; Anne Preston ; Brooke Augustine ; Charla Andrews ; Galina V Yamshchikov ; Somia Hickman ; Steven Schech ; Jack N Hutter ; Paul T Scott ; Paige E Waterman ; Mihret F Amare ; Victoria Kioko ; Casey Storme ; Kayvon Modjarrad ; Melanie D McCauley ; Merlin L Robb ; Martin R Gaudinski ; Ingelise J Gordon ; LaSonji A Holman ; Alicia T Widge ; Larisa Strom ; Myra Happe ; Josephine H Cox ; Sandra Vazquez ; Daphne A Stanley ; Tamar Murray ; Caitlyn N M Dulan ; Ruth Hunegnaw ; Sandeep R Narpala ; Phillip A Swanson ; Manjula Basappa ; Jagada Thillainathan ; Marcelino Padilla ; Britta Flach ; Sarah O'Connell ; Olga Trofymenko ; Patricia Morgan ; Emily E Coates ; Jason G Gall ; Adrian B McDermott ; Richard A Koup ; John R Mascola ; Aurélie Ploquin ; Nancy J Sullivan ; Julie A Ake ; Julie E Ledgerwood ; RV 507 Study Team

BACKGROUND:

WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults.

METHODS:

We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10¹⁰ or 1 × 10¹¹ particle units (pu). Primary safety endpoints included reactogenicity assessed for the first 7 days and all adverse events assessed for 28 days after vaccination. Secondary immunogenicity endpoints were assessment of binding antibody responses and T-cell responses against the Marburg virus glycoprotein insert, and assessment of neutralising antibody responses against the cAd3 vector 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT03475056.

FINDINGS:

Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10¹⁰ pu (n=20) or 1 × 10¹¹ pu (n=20). The cAd3-Marburg vaccine was safe, well tolerated, and immunogenic. All enrolled participants received cAd3-Marburg vaccine, with 37 (93%) participants completing follow-up visits; two (5%) participants moved from the area and one (3%) was lost to follow-up. No serious adverse events related to vaccination occurred. Mild to moderate reactogenicity was observed after vaccination, with symptoms of injection site pain and tenderness (27 [68%] of 40 participants), malaise (18 [45%] of 40 participants), headache (17 [43%] of 40 participants), and myalgia (14 [35%] of 40 participants) most commonly reported. Glycoprotein-specific antibodies were induced in 38 (95%) of 40 participants 4 weeks after vaccination, with geometric mean titres of 421 [95% CI 209-846] in the 1 × 10¹⁰ pu group and 545 [276-1078] in the 1 × 10¹¹ pu group, and remained significantly elevated at 48 weeks compared with baseline titres (39 [95% CI 13-119] in the 1 ×10¹⁰ pu group and 27 [95-156] in the 1 ×10¹¹ pu group; both p<0·0001). T-cell responses to the glycoprotein insert and neutralising responses against the cAd3 vector were also increased at 4 weeks after vaccination.

INTERPRETATION:

This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions.

FUNDING:

National Institutes of Health.

项与 VRC-MARADC087-00-VP 相关的新闻（医药）

2023-01-30

·Science Daily

Marburg vaccine shows promising results in first-in-human study

A new article shows that an experimental vaccine against Marburg virus (MARV) was safe and induced an immune response in a small, first-in-human clinical trial. The vaccine could someday be an important tool to respond to Marburg virus outbreaks. A newly published paper in The Lancet shows that an experimental vaccine against Marburg virus (MARV) was safe and induced an immune response in a small, first-in-human clinical trial. The vaccine, developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, could someday be an important tool to respond to Marburg virus outbreaks. This first-in-human, Phase 1 study tested an experimental MARV vaccine candidate, known as cAd3-Marburg, which was developed at NIAID's Vaccine Research Center (VRC). This vaccine uses a modified chimpanzee adenovirus called cAd3, which can no longer replicate or infect cells, and displays a glycoprotein found on the surface of MARV to induce immune responses against the virus. The cAd3 vaccine platform demonstrated a good safety pro prior clinical trials when used in investigational Ebola virus and Sudan virus vaccines developed by the VRC. MARV, a filovirus in the same family as Ebola virus, causes a rapidly progressive febrile illness that leads to shock and death in a large proportion of infected individuals. Many scientists think that MARV disease outbreaks in humans begin by when the virus makes the jump from its primary animal host, which is likely to be certain chronically infected bats in sub-Saharan Africa. The symptoms of MARV disease are akin to those seen with Ebola virus disease and can include fever, headache, chills, rash, abdominal pain, vomiting, and diarrhea. As the disease progresses, patients may suffer from multiple organ dysfunction, delirium, and significant bleeding from the gastrointestinal tract or other sites that may result in death. No approved vaccines or specific therapies are available for MARV disease, aside from supportive care. While some experimental vaccines have previously been tested, none have proven to be both highly effective and to provide durable protection. In areas of Africa where a vaccine for Marburg is most needed, a single-dose vaccine that could protect recipients over a long period of time would be a crucial part of quelling outbreaks. In this study, 40 healthy adult volunteers were enrolled at the Walter Reed Army Institute of Research Clinical Trials Center in Silver Spring, Maryland. They received a single dose of either a low dose of the vaccine (1x1010 particle units) or a higher dose (1x1011 particle units). For safety, the volunteers were enrolled in a dose-escalation plan. Three participants received the lower dose. Then, when they did not exhibit severe adverse reactions after the first seven days, the trial proceeded to enroll the remaining 17 volunteers. The same procedure was also used for the higher dose group. Volunteers were monitored for adverse reactions to the investigational vaccine and evaluated at regular intervals for 48 weeks to track their immune responses. The trial's safety results were encouraging: There were no serious adverse events, and the experimental vaccine was well-tolerated. One participant in the higher dose group developed a fever following vaccination, but it resolved by the following day. In addition, the investigational vaccine appeared to induce strong, long-lasting immunity to the MARV glycoprotein: 95% of participants in the trial exhibited a robust antibody response after vaccination, and 70% maintained that response for more than 48 weeks. Plans are in place to conduct further trials of the cAd3-Marburg vaccine in Ghana, Kenya, Uganda, and the United States. If additional data supports the promising results seen in the Phase 1 trial, the cAd3-Marburg virus vaccine could someday be used in emergency responses to MARV outbreaks.

疫苗临床1期临床结果

2023-01-25

·PRNewswire

EverGlade Consulting Helps Sabin Vaccine Institute Secure up to $214 Million in BARDA Funding to Develop and Procure Ebola Sudan and Marburg Vaccines

CHARLESTON, S.C. , Jan. 25, 2023 /PRNewswire/ -- EverGlade Consulting ("EverGlade"), a national consulting firm, has helped Sabin Vaccine Institute successfully secure up to $214 million in funding through a contract with the Biomedical Advanced Research and Development Authority ("BARDA") to advance the development and production of single-dose vaccine candidates for Ebola Sudan and Marburg virus diseases. Currently, there are no licensed vaccines against Ebola Sudan and Marburg viruses, which cause hemorrhagic fever and kill approximately half the people infected. Continue Reading EverGlade Consulting has successfully secured up to $214 million in funding through a contract with BARDA to advance the development and production of single-dose vaccine candidates for Ebola Sudan and Marburg virus diseases. BARDA, part of the U.S. Department of Health and Human Services' Administration for Strategic Preparedness and Response ("ASPR"), will initially invest $35 million to produce up to 100,000 doses of Ebola Sudan virus vaccine, ChAd3-SUDV. These vaccines may be used as part of ongoing U.S. preparedness efforts and in response to future global outbreaks. The contract also includes funding to manufacture Sabin's Marburg virus vaccine, ChAd3-MARV, which will generate doses that could be used in trials and in response to a future Marburg virus outbreak. "I am excited that our team was able to contribute to this vital BARDA initiative," said EverGlade Founder Eric Jia-Sobota. "This award addresses a critical need." Andrew Stiles, Principal at EverGlade, said, "The recent Ebola Sudan outbreak in Uganda emphasized the critical need for better preparedness. It is great to see BARDA move quickly to partner with industry to develop and secure readily available solutions to address this threat and to bolster national preparedness and response efforts for future public health emergencies." About EverGlade Consulting EverGlade Consulting is a national consulting firm helping clients navigate the federal landscape. We work with technology-driven companies whose focus is to secure non-dilutive funding through the federal government. We offer services ranging from opportunity identification and proposal support through the implementation of systems to comply with federal regulations at agencies including BARDA, ASPR, NIH, DTRA, JPEO, and DARPA. For additional information about EverGlade Consulting, visit: For additional information about EverGlade's recent success, visit: SOURCE EverGlade Consulting

疫苗临床研究

2021-06-17

·GlobeNewswire

Marburg Virus Disease Pipeline Offers Promising New Options

Los Angeles, USA, June 16, 2021 (GLOBE NEWSWIRE) -- Marburg Virus Disease Pipeline Offers Promising New Options for Treatment Around 12+ key companies are developing the Marburg Virus Disease therapies. Bavarian Nordic is developing the MVA-BN filovirus vaccine, which is in the most advanced stage. DelveInsight’s “Marburg Virus Disease Pipeline Insight” report provides comprehensive insights about 12+ companies and 12+ pipeline drugs in the Marburg Virus Disease pipeline landscapes. It comprises Marburg Virus Disease pipeline drug profiles, including clinical and non-clinical stage products. It also includes the Marburg Virus Disease therapeutics assessment by product type, stage, route of administration, and molecule type and further highlights the inactive Marburg Virus Disease pipeline products. Some of the key takeaways from the Marburg Virus Disease Pipeline Report Get an overview of pipeline landscape @ Marburg Virus Disease Clinical Trials Analysis Marburg Virus Disease is a highly virulent disease, which causes hemorrhagic fever. It belongs to the same family that causes Ebola virus disease. There is no particular treatment for Marburg hemorrhagic fever. Instead, supportive hospital therapy should be utilized, including balancing the patient’s fluids and electrolytes, maintaining oxygen status and blood pressure, replacing lost blood and clotting factors, and treating any complicating infections. Marburg Virus Disease Emerging Drugs Galidesivir (BCX4430) is a broad-spectrum antiviral in advanced development for the virus treatment. BioCryst is developing galidesivir in partnership with U.S. government agencies and other institutions. In September 2013, NIAID contracted with BioCryst to develop galidesivir to treat Marburg Virus Disease and potentially for other filoviruses, including the Ebola virus. The drug is currently in phase 1 of clinical trials for the treatment of Marburg Virus Disease. Research and Development Phase I NCT03800173: BioCryst Pharmaceuticals, in December 2018, initiated “A Phase 1 Double-blind, Placebo Controlled, Dose Ranging Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Galidesivir (BCX4430) Administered as Single Doses Via Intravenous Infusion in Healthy Subjects”. This is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics of galidesivir following administration of single doses by IV infusion. This single ascending dose study will assess the safety, tolerability, and PK of single doses of galidesivir vs. placebo administered as IV infusions in healthy subjects enrolled in up to four dose cohorts of 8 subjects each. A single dose of study drug will be administered per cohort: 6 subjects will receive galidesivir IV, and two subjects will receive matching placebo. The trial got completed in April 2019 with 32 enrolled participants. Results MVA-BN Filo is a multivalent vaccine candidate designed to protect against the most common causes of viral hemorrhagic fever; Ebola and the Marburg virus. While several sub-types of Ebola are known, the vaccine targets the Zaire and Sudan strains, which are considered the most important from a public health perspective in addition various. It is currently in phase 2 of clinical trials for the treatment of Marburg Virus Disease. cAd3-Marburg, also known as VRC MARADC087 00 VP, is being developed and investigated by Albert B. Sabin Vaccine Institute, ICON plc, and Oklahoma Blood Institute in Phase I stage of development for the treatment of patients with Marburg virus disease. Research and Development Phase INCT04723602: In January 2021, a trial was initiated by ICON plc in collaboration with Sabin vaccine institute titled “Phase 1b Trial to Evaluate Safety, Tolerability and Immune Responses of 2 Monovalent Chimpanzee Adenoviral Vectored Filovirus (Ebola-S and Marburg) Vaccines to Healthy Adults, Collection of Plasma/Serum for the Purposes of Assay Development”. The primary objective is to evaluate the safety and tolerability of cAd3-EBO-S and cAd3 Marburg vaccines when administered Intramuscular (IM) at a dose of 1 x 10^11 particle units (PU) to healthy adults. The trial is anticipated to get completed in December 2021 with an estimated enrollment of 32 participants. For further information, refer to the detailed report @ Marburg Virus Disease Pipeline Therapeutics Scope of Marburg Virus Disease Pipeline Drug Insight · Marburg Virus Disease Therapies Late-stage (Phase III) · Marburg Virus Disease Therapies Mid-stage (Phase II)· Marburg Virus Disease Therapies Early-stage (Phase I) · Marburg Virus Disease Pre-clinical stage and Discovery candidates · Discontinued and Inactive candidates · RNA replicase inhibitors· Immunostimulants· Virus replication inhibitors · Peptides· Monoclonal Antibody· Polymer· Small molecule· Gene therapy · Oral· Parenteral· Intravenous· Subcutaneous· Topical · Monotherapy· Combination· Mono/Combination Key Questions regarding Current Marburg Virus Disease Treatment Landscape and Emerging Therapies Answered in the Pipeline Report Table of Contents Get a customized pipeline report @ Marburg Virus Disease Drugs Pipeline Report Related Reports DelveInsight's 'Central Venous Catheters Market Insights, Competitive Landscape and Market Forecast-2026' report delivers an in-depth understanding of Central Venous Catheters. 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基因疗法抗体疫苗小分子药物合作

100 项与 VRC-MARADC087-00-VP 相关的药物交易

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