Delving into the Latest Updates on Clostridium difficile vaccine(Valneva/GlaxoSmithKline) with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms

Clostridium difficile vaccine(Valneva/Novartis), IC-84, VLA 84

+ [1]

Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious Diseases

Active Indication-

Inactive Indication

Clostridium difficile infectionClostridium Infections

Originator Organization

Intercell AG

Active Organization-

Inactive Organization

Valneva Austria GmbH

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

Gene Sequence

Sequence Code 1120173660

Phase 2, randomized, observer-blind, placebo-controlled, multi-centric study including 4 parallel study groups.
500 Subjects (thereof, 250 aged 50 - 64 years and 250 aged 65 years and older) will be randomized in a (3:3:3:1) ratio to receive either VLA84 75 µg w/o (without) Alum, VLA84 200 µg w/o Alum, VLA84 200 µg w/ (with) Alum (150 subjects each), or placebo (50 subjects), as i.m. (intramuscular) vaccinations into alternating arms, on Days 0, 7 and 28

Start Date01 Dec 2014

Sponsor / Collaborator

Valneva Austria GmbH

NCT01296386 / CompletedPhase 1

An Open-label Phase 1 Study Assessing the Safety, Immunogenicity and Dose Response of IC84, a New Vaccine Against Clostridium Difficile, in Healthy Subjects

An open-label Phase 1 Study Assessing the Safety, Immunogenicity and Dose Response of IC84, A new vaccine against Clostridium Difficile (C. difficile), In healthy subjects

Start Date01 Dec 2010

Sponsor / Collaborator

Valneva Austria GmbH

100 Clinical Results associated with Clostridium difficile vaccine(Valneva/GlaxoSmithKline)

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100 Translational Medicine associated with Clostridium difficile vaccine(Valneva/GlaxoSmithKline)

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100 Patents (Medical) associated with Clostridium difficile vaccine(Valneva/GlaxoSmithKline)

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14

Literatures (Medical) associated with Clostridium difficile vaccine(Valneva/GlaxoSmithKline)

01 Aug 2019·Infection and immunityQ2 · MEDICINE

Vaccination against Clostridium difficile by Use of an Attenuated Salmonella enterica Serovar Typhimurium Vector (YS1646) Protects Mice from Lethal Challenge

Q2 · MEDICINE

Article

Author: Winter, Kaitlin ; Ward, Brian J. ; Xing, Li ; Kassardjian, Audrey

01 May 2016·VaccineQ3 · MEDICINE

Safety, immunogenicity and dose response of VLA84, a new vaccine candidate against Clostridium difficile, in healthy volunteers

Q3 · MEDICINE

Article

Author: Kiermayr, Sigrid ; Ayad, Andrea ; Jilma, Bernd ; Dubischar, Katrin ; Pinl, Fritz ; Hochreiter, Romana ; Westritschnig, Kerstin ; Bézay, Nicole ; Firbas, Christa ; Kiss, István

BACKGROUND:

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea and colitis and the most common pathogen of health care-associated infections. In the US, CDI causes approximately half a million infections and close to 30,000 deaths. Despite antibiotic treatment of C. difficile associated diarrhoea, the disease is complicated by its recurrence in up to 30% of patients.

METHODS:

An open-label, partially randomized, dose-escalation Phase I trial was performed in two parts. Sixty volunteers aged ≥18 to <65 years were randomized into five treatment groups to receive three immunizations (Day 0, 7, 21) of VLA84 (20μg with Alum, 75μg with or without Alum, 200μg with or without Alum). Eighty-one volunteers aged ≥65 were randomized into four treatment groups (75μg with or without Alum, 200μg with or without Alum) and received four immunizations (Day 0, 7, 28 and 56). All subjects were followed for safety and immunogenicity for six months.

RESULTS:

VLA84 was safe and well tolerated. Fifty-one adult volunteers (85%) and 50 elderly (62%) experienced at least one solicited or unsolicited adverse event (AE). Forty-eight adult volunteers (80%) and 40 elderly (49%) experienced related AEs which were mostly mild or moderate. No related serious adverse event and no death occurred. The vaccine induced high antibody titres against Toxin A and Toxin B in both study populations.

CONCLUSION:

VLA84 was safe, well tolerated and highly immunogenic in adult volunteers aged ≥18 to <65 years and elderly volunteers aged ≥65 years. This study is registered at ClinicalTrials.gov under registration number NCT01296386.

01 Nov 1996·Infection and immunityQ2 · MEDICINE

Effects of Clostridium difficile toxin A and toxin B on phospholipase D activation in human promyelocytic leukemic HL60 cells

Q2 · MEDICINE

Article

Author: Nozawa, Y ; Lyerly, D M ; Watanabe, K ; Banno, Y ; Nakashima, S ; Kato, N ; Ohguchi, K

The possible involvement of Rho family GTP-binding proteins in the regulation of phospholipase D (PLD) activity has recently been demonstrated. In the present study, to further examine the role of Rho family proteins in PLD activation of human promyelocytic leukemic HL60 cells, we used toxin A and toxin B from the anaerobic bacterium Clostridium difficile, which was shown to glucosylate Rho family proteins and inhibit their interaction with effectors. Pretreatment of [3H]oleic acid-labeled HL60 cell lysates with either one of the toxins resulted in a remarkable inhibition of membrane PLD activity stimulated by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). The magnitude of inhibition of PLD activity was correlated well with the extent of toxin A- or B-induced glucosylation of 22-kDa RhoA in HL60 cells, toxin B being more effective than toxin A. GTPgammaS-stimulated PLD activation measured with the exogenous substrate containing phosphatidylinositol 4,5-bisphosphate was also inhibited by toxin B. Toxin B had no effect on GTP-gammaS-induced translocation of RhoA from cytosol to membranes. Furthermore, the toxin B pretreatment also suppressed PLD activation induced by 4beta-phorbol 12-myristate 13-acetate in HL60 cell lysates. Thus, it was indicated that Rho family proteins play a key role in GTPgammaS- and 40-phorbol 12-myristate 13-acetate-induced PLD activity in HL60 cells. In addition, the results obtained here indicate that C. difficile toxins are a useful tool for researching the regulation of the Rho family protein-mediated PLD activation and also provide a clue toward understanding the pathogenic background of pseudomembranous colitis from the viewpoint of signal transduction.

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News (Medical) associated with Clostridium difficile vaccine(Valneva/GlaxoSmithKline)

01 Dec 2017

·www.globenewswire.com

Sanofi ends development of Clostridium difficile vaccine

Press Release Source: Sanofi (EURONEXT: SAN) (NYSE: SNY) Sanofi ends development of Clostridium difficile vaccine Paris, France - December 1, 2017 - Following a planned interim analysis, the Independent Data Monitoring Committee (IDMC) for the phase III Cdiffense clinical trial program concluded that the probability that the study will meet its primary objective is low. Based on this, Sanofi has therefore decided to discontinue clinical development of its experimental Clostridium difficile vaccine, to focus on six key vaccine projects currently in development. Cdiffense is a trial designed to test the efficacy and safety of a candidate toxoid vaccine in a subpopulation at risk of Clostridium difficile infection. Sanofi Pasteur, the vaccines business of Sanofi responsible for the program, is informing all investigators, regulatory authorities and trial ethics committees. In addition, investigators are notifying study volunteers of the decision to stop the program. Data from all vaccinated volunteers in this trial will continue to be analyzed for more information and shared with the scientific community. About Sanofi Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions. With more than 100,000 people in 100 countries, Sanofi is transforming scientific innovation into healthcare solutions around the globe. Sanofi, Empowering Life Media Relations Contact Laurence Bollack Tel. : +33 (0)1 53 77 46 46 mr@sanofi.com Investor Relations Contact George Grofik Tel.: +33 (0)1 53 77 45 45 ir@sanofi.com

Vaccine

100 Deals associated with Clostridium difficile vaccine(Valneva/GlaxoSmithKline)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Clostridium Infections	Phase 2	US	Valneva Austria GmbH	01 Dec 2014
Clostridium Infections	Phase 2	DE	Valneva Austria GmbH	01 Dec 2014
Clostridium difficile infection	Phase 1	AT	Valneva Austria GmbH	01 Dec 2010
Clostridium difficile infection	Phase 1	HU	Valneva Austria GmbH	01 Dec 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2022	Not Applicable	Solid tumor	-	Clostridioides difficile infections (Patients with solid tumors and C. diff colitis)	zkzttstxib(ovrmckkqyv): AOR = 1.91 (95% CI, 1.73 - 2.1) View more	-	02 Jun 2022
				Clostridioides difficile infections (Patients without underline solid tumor and C. diff colitis)
NCT02316470 (CTgov)	Phase 2	Clostridium Infections	500	Placebo+VLA84 (VLA84 75 mcg (Microgram) w/o Alum)	ngeuzujajz(hfvrhqhtdx) = bqxpwazebs hlwwhqljon (dljihzvlyt, tqnxojryly - gbenpwdrpa) View more	-	08 Jun 2017
				VLA84 (VLA84 200 mcg w/o Alum)	ngeuzujajz(hfvrhqhtdx) = dqqcsbsviu hlwwhqljon (dljihzvlyt, tybtbhostk - ytowneicpl) View more
NCT01296386 (Pubmed \| Vaccine) Manual	Phase 1	-	141	VLA84	jmlebbpblp(vhvyltfifo) = adult volunteers (80%) and 40 elderly (49%) qrxjuyuupb (zwecdjbucm )	Positive	17 May 2016