Delving into the Latest Updates on PF-6425090 with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms

Clostridium difficile vaccine, Toxoid-based Clostridium difficile vaccine

+ [1]

Target

TcdA x toxB

Mechanism

TcdA inhibitors(TcdA inhibitors), toxB inhibitors(Toxin B inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Clostridium difficile infection

Inactive Indication

Clostridium difficile colitis

Originator Organization

Pfizer Inc.

Active Organization

Pfizer Japan, Inc.

Inactive Organization

Pfizer Inc.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 4709750

Sequence Code 4709758

This study will investigate a Clostridium difficile vaccine in adults 50 years of age and older. In half the adults, all 3 doses given are the Clostridium difficile vaccine, and in half the adults, 2 of the 3 doses are the Clostridium difficile vaccine with the other dose containing no active ingredients. The study will look at the subjects' immune response to the vaccine and assess the safety and tolerability of a 2-dose regimen of Clostridium difficile vaccine compared to a 3-dose regimen of Clostridium difficile vaccine.

Start Date01 Apr 2019

Sponsor / Collaborator

Pfizer Inc.

NCT03579459

/ CompletedPhase 3

A PHASE 3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE LOT CONSISTENCY, SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A CLOSTRIDIUM DIFFICILE VACCINE IN HEALTHY ADULTS 65 TO 85 YEARS OF AGE

This study will investigate a Clostridium difficile vaccine in healthy adults 65 to 85 years of age, who will each receive 3 doses of vaccine. The study will assess the lot consistency, safety, and tolerability of the vaccine, and also look at the subjects' immune response to the vaccine.

Start Date31 Jul 2018

Sponsor / Collaborator

Pfizer Inc.

NCT03090191

/ CompletedPhase 3

A PHASE 3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF A CLOSTRIDIUM DIFFICILE VACCINE IN ADULTS 50 YEARS OF AGE AND OLDER

The Clover trial is evaluating an investigational vaccine that may help to prevent Clostridium difficile infection. Participants in the study are adults 50 years of age and older, who are at risk of developing Clostridium difficile infection. The study will assess whether the vaccine prevents the disease, and whether it is safe and well tolerated.
Each subject will receive 3 doses of Clostridium difficile vaccine or placebo and be followed for up to 3 years after vaccination for potential Clostridium difficile infection.

Start Date29 Mar 2017

Sponsor / Collaborator

Pfizer Inc.

100 Clinical Results associated with PF-6425090

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100 Translational Medicine associated with PF-6425090

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100 Patents (Medical) associated with PF-6425090

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20

Literatures (Medical) associated with PF-6425090

17 Dec 2024·Clinical Infectious Diseases

CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection

Article

Author: Bouguermouh, Salim ; Wilcox, Mark H ; Donskey, Curtis J ; Klein, Nicola P ; Gruber, William C ; Dubberke, Erik R ; Jansen, Kathrin U ; Lawrence, Jody ; Anderson, Annaliesa S ; Koury, Kenneth ; Pride, Michael W ; Kitchin, Nicholas ; Lockhart, Stephen ; Bailey, Ruth ; Zhang, Haiying ; Webber, Chris ; Szymkowiak, Katarzyna ; Smith, Helen M ; Kalina, Warren V ; Lamberth, Erik ; Liles, Elizabeth G

AbstractBackgroundClostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.MethodsThis phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed.ResultsThe primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE) = 31.0% (96.4% confidence interval [CI], −38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE = 28.6% (96.4% CI, −28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P = .02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE = 100%; 95% CI, 59.6% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups.ConclusionsThree PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden.Clinical Trials RegistrationNCT03090191.

01 Nov 2024·Toxicon

Protection efficacy and immunogenicity of Clostridium chauvoei proteins as a subunit blackleg vaccine or an adjuvant for Clostridium perfringens epsilon toxoid

Article

Author: Hamzavipour, Roxana ; Zahmatkesh, Azadeh ; Paradise, Alireza ; Hosseini, Farzaneh

Potential application of Clostridium chauvoei proteins was studied as a subunit blackleg vaccine or a biological adjuvant for Clostridium perfringens epsilon toxoid vaccine. Extracellular and cell surface proteins were extracted from C. chauvoei culture, and their protective efficacy was evaluated by potency test in guinea pigs. In order to investigate the effect of cell surface proteins on C. perfringens epsilon toxoid immunogenicity, rabbits were inoculated subcutaneously twice with: C. perfringens type D toxoid supernatant +200 μg C. chauvoei cell surface proteins (PR-200), toxoid supernatant + 400 μg cell surface proteins (PR-400), inactivated C. perfringens type D vaccine (Vac), toxoid supernatant (Tox), or PBS. Isolation of cell surface proteins yielded about 2.5 mg/L culture protein with a sharp band at 43 kDa probably corresponding to flagellin. Potency test demonstrated the protection ability of both cellular and extracellular proteins of C. chauvoei. ELISA showed that the highest antibody titers against epsilon toxoid belonged to PR-400 and Vac groups. The effect of days post immunization on antibody response was not significant. No significant difference was observed between PR-400 and Vac, as well as PR-200 and Tox groups. Clostridium chauvoei cell surface proteins may have the potential for application as a blackleg disease vaccine and an adjuvant for clostridial toxoids.

01 Jan 2024·Advances in Experimental Medicine and Biology

Clostridioides difficile Infections: Prevention and Treatment Strategies

Review

Author: Vandenplas, Yvan ; Levy, Elvira Ingrid ; Dinleyici, Meltem ; Dinleyici, Ener

Clostridioides difficile is the most common causative agent of antibiotic-associated diarrhea. This spore forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, more recent fecal microbiota transplantation has also been valid as a therapy. The use of probiotics, especially Saccharomyces boulardii CNCM I-745 have become valid forms of prevention therapy. Although there are studies in adults with microbiota-targeted new generation therapies and Clostridium difficile vaccines, there are no data in the paediatric age group yet.

100 Deals associated with PF-6425090

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Clostridium difficile infection	Phase 2	SE	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Phase 2	CA	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Phase 2	PL	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Phase 2	PE	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Phase 2	US	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Phase 2	ES	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Phase 2	AU	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Phase 2	BG	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Phase 2	PT	Pfizer Inc.	29 Mar 2017
Clostridium difficile infection	Discovery	AR	Pfizer Inc.	29 Mar 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03918629 (CTgov)	Phase 3	Clostridium difficile colitis	1,994	Clostridium Difficile Vaccine (2-Dose Clostridium Difficile Vaccine)	ilgahygyae(yizvkojdyw) = qujovrcpdh yrofjmhejt (itwbmwmhrv, qlboghmwnl - vevvsifzgt) View more	-	10 Jan 2024
				Clostridium Difficile Vaccine (3-Dose Clostridium Difficile Vaccine)	ilgahygyae(yizvkojdyw) = kdqhwctldg yrofjmhejt (itwbmwmhrv, vzyxzucrhx - fxzhapuvmd) View more
NCT03090191 (CLOVER, CTgov)	Phase 3	Clostridium difficile infection	17,535	Clostridium difficile vaccine (Clostridium Difficile Vaccine)	oxxwtgfili(jdzqkkyzvd) = kkgthstjbd fuhrhybhst (lqrspouxud, dpymyavjum - hbkjmfamee) View more	-	13 Feb 2023
				Placebo (Placebo)	oxxwtgfili(jdzqkkyzvd) = grmzgekxug fuhrhybhst (lqrspouxud, vsicmrfhzs - zwvhprkuxo) View more
NCT03579459 (CTgov)	Phase 3	Clostridium difficile colitis	1,317	placebo	tpxroaehjz(ctspbdkkqt) = vamsgnnhkd gjyhstbntc (rcjlrjgkeq, awpmjrwjlv - uqldumgagw) View more	-	19 Jan 2023
NCT03090191 (CLOVER, BusinessWire) Manual	Phase 3	Clostridium difficile infection	17,500	PF-6425090	(aywzvgntab) = Local and systemic reactions were mild to moderate, with mostly pain at the injection site with higher incidence after the second and third doses. The number of participants reporting overall adverse events (AEs), serious AEs (SAEs), withdrawals and deaths were similar between the two groups. gfmluqajju (dwjjmicanz )	Negative	01 Mar 2022
				Placebo
NCT02117570 (CTgov)	Phase 2	Clostridium difficile colitis	185	Placebo	eoiamzgpuw(fsiemqmced) = ztdpwpkzij eqfiysjarp (hzhlypjlox, iqdswgxzxn - eepayvimou) View more	-	30 Jan 2017