AZD5148 for C. diff Infection

(PRISM Trial)

Recruiting at 94 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Fidaxomicin, Vancomycin, Metronidazole

Must not be taking: Bezlotoxumab, Fecal transplant

Disqualifiers: Inflammatory bowel disease, Ostomy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 1 day

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD5148 to determine if it can prevent the recurrence of Clostridioides difficile (C. diff) infections. C. diff is a type of bacteria that causes serious diarrhea and gut issues. Participants will receive either AZD5148 or a placebo to assess which is more effective. Individuals who recently had a C. diff infection and are on specific antibiotics might qualify for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on a standard antibacterial drug therapy for C. difficile infection, like fidaxomicin, vancomycin, or metronidazole, for at least 10 days and no more than 25 days when starting the trial medication.

Is there any evidence suggesting that AZD5148 is likely to be safe for humans?

Research has shown that AZD5148 has undergone safety testing in people. In one study with healthy Japanese participants, a single dose of AZD5148 was administered either through an IV (a needle into a vein) or an IM injection (a shot into a muscle) and was generally well-tolerated, meaning most participants did not experience serious side effects. These findings suggest that AZD5148 might be safe for preventing recurrent C. difficile infections. However, discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for C. diff infection?

Unlike the standard treatments for C. diff infections, which often include antibiotics like vancomycin and metronidazole, AZD5148 offers a fresh approach. Researchers are excited about AZD5148 because it introduces a new mechanism of action by potentially targeting the specific toxins produced by C. diff bacteria, rather than just eliminating the bacteria themselves. Additionally, AZD5148 can be administered as a single dose via intramuscular injection or intravenous push, offering a more convenient and potentially quicker treatment option than the typical prolonged antibiotic courses. This innovative approach could lead to more effective management of C. diff infections with reduced recurrence rates.

What evidence suggests that AZD5148 might be an effective treatment for C. diff infection?

Research shows that AZD5148, which participants in this trial may receive, might help prevent the recurrence of C. diff infections. Studies have found that this treatment can fight many types of C. diff bacteria in lab tests, suggesting it could work against different strains. In animal studies, AZD5148 successfully protected against C. diff infections. The treatment targets specific parts of the bacteria that have remained unchanged over time, making it a promising option for preventing infections from returning. Since C. diff infections often reoccur, a treatment like AZD5148 could be important in reducing the risk of reinfection. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults who have had a Clostridioides difficile infection and are at risk of it coming back. The study is looking for participants over the age of 18.

Inclusion Criteria

I am currently being treated for a C. difficile infection confirmed by a positive toxin test.

I weigh at least 40 kg.

I am 18 or older and can sign the consent form.

Exclusion Criteria

I have not had my entire colon removed or weight loss surgery that changes my digestive system.

I haven't had a fecal transplant or similar treatment in the last 6 months.

I have a history of inflammatory bowel disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Up to 2 visits (in-person)

Treatment

Participants receive a single dose of either AZD5148 or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including weekly and later monthly follow-ups

12 months

Up to 7 planned visits, with additional contacts initiated by site staff

What Are the Treatments Tested in This Trial?

Interventions

• AZD5148

Trial Overview

The study tests whether AZD5148, a monoclonal antibody, can prevent C. diff infections from returning compared to a placebo (a substance with no active drug).

How Is the Trial Designed?

Group I: AZD5148: dose A Experimental Treatment 1 Intervention

Participants will receive a single dose A of AZD5148 administered via either intramuscular injection or intravenous push.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive a single dose of placebo via intramuscular or intravenous push.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07285213

Prevention of Recurrent C. Difficile Infection Study With ...

The purpose of this study is to evaluate the efficacy and safety of AZD5148 for prevention of recurrence of Clostridioides difficile infection ...

2.

academic.oup.com

academic.oup.com/jid/article/232/5/e741/8234296

Epitope Conservation of AZD5148, a Broadly Neutralizing Anti ...

We report a high degree of AZD5148 binding site epitope conservation from 2015 to 2024. AZD5148 showed broad in vitro neutralization, except in RT-017 with.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12594360/

The monoclonal antibody AZD5148 confers broad ...

In this study, we evaluated the protective efficacy of AZD5148 in vitro and in vivo against clinically relevant C. difficile strains expressing ...

4.

astrazeneca.com

astrazeneca.com/content/astraz/what-science-can-do/topics/disease-understanding/rethinking-prevention-of-recurrent-c-diff-infections.html

C. diff infections and rethinking prevention

About 1 in 6 patients who get a CDI will experience a recurrence within 8 weeks – some within days – and their risk of recurrent infections gets ...

5.

astrazenecaclinicaltrials.com

astrazenecaclinicaltrials.com/study/D8820C00005

Safety and tolerability of AZD5148 in Japanese participants

The purpose of this study is to measure safety, tolerability and PK of a single dose of AZD5148 administered via IV bolus or IM injection in healthy Japanese ...