Recurrent Clostridioides Difficile Infection
Conditions
Keywords
Cdiff Infection, Clostridiodes difficile infection, Cdiff
Brief summary
This is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 (doses of either 250 mg or 500 mg PO every 12 hours) for the reduction of Clostridioides difficile infection (CDI).
Detailed description
Study was terminated due to sponsor decision. This decision was not related to safety concerns.
Interventions
DRUGREC-3964
REC-3964 given at a dose of either 500 mg q12h or 250 mg q12h
Sponsors
Recursion Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 115 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Be 18 years of age or older with Clostridioides difficile infection (CDI) diarrhea associated with a positive stool test for C. difficile toxin\[s\] prior to the preceding curative treatment. * The CDI episode, severe or otherwise, must have resolved after receiving vancomycin with a standard duration of treatment. The participant must be randomized within 2 days of completing the preceding curative treatment. * Have high risk for rCDI (a recurrent CDI episode within the last 6 months, age ≥65 years, immunocompromised state, or severe CDI with resolution prior to enrollment into the study). Key
Exclusion criteria
* Have an active, symptomatic, chronic diarrheal illness from other causes, such as ulcerative colitis or Crohn's disease. * Diarrhea that requires on-study treatment with agents that would confound the interpretation of the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Survival Without Recurrence or Requirement for Additional Clostridioides Difficile Infection (CDI) Treatment | 8 weeks | Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin or requirement for additional CDI treatment during the 8-week Follow-up Period after cure of preceding CDI with initial curative treatment. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 8 weeks | A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. |
| Number of Participants With Related TEAEs | Up to 8 weeks | A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An Investigator who was qualified in medicine determined relationship to the study drug for each AE (unrelated or related). The Investigator decided whether, in his or her medical judgment, if there was a reasonable biological possibility that the event may have been caused by the study drug. |
| Number of Participants With Serious TEAEs | Up to 8 weeks | A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A Serious TEAE was defined as results in death, immediately life-threatening, requires in-participant hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity in conducting activities of daily living for at least 28 days, results in a congenital abnormality or birth defect, or an important medical event that may jeopardize the participant or may require medical intervention. |
| Number of Participants With TEAEs Leading to Study Drug Discontinuation | Up to 8 weeks | A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma Concentration (Tmax) of REC-3964 | Pre-dose, 1 hour, 3 hours, and 6 hours post morning dose on the Day 1 and Day 15 | — |
| Rate of Recurrent Clostridioides Difficile Infection (rCDI) | 8 weeks | Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin within 8 weeks of the cessation of initial curative treatment. The number of unformed \[types 5-7 on the Bristol stool scale\] bowel movements per day were recorded by the participant in the stool diary in order to identify a new episode of diarrhea. All new episodes of diarrhea were tested for toxigenic Clostridioides difficile to confirm CDI recurrence. The rate of rCDI was defined as the proportion of participants who had the Clostridioides difficile recurrence among randomized participants. |
| Trough Plasma Concentration (Ctrough) of REC-3964 | Pre-dose on Day 15 | — |
| Time to Recurrence of rCDI | Up to 8 weeks | Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin within 8 weeks of the cessation of initial curative treatment. The number of unformed \[types 5-7 on the Bristol stool scale\] bowel movements per day were recorded by the participant in the stool diary in order to identify a new episode of diarrhea. All new episodes of diarrhea were tested for toxigenic Clostridioides difficile to confirm CDI recurrence. Time to recurrence of rCDI was to be assessed using Kaplan-Meier estimation. |
| Number of Participants With Severe rCDI | Up to 8 weeks | Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin within 8 weeks of the cessation of initial curative treatment. The number of unformed \[types 5-7 on the Bristol stool scale\] bowel movements per day were recorded by the participant in the stool diary in order to identify a new episode of diarrhea. All new episodes of diarrhea were tested for toxigenic Clostridioides difficile to confirm CDI recurrence. Severe CDI was defined as CDI with white blood cell count \>15,000 cells/milliliter and/or serum creatinine ≥1.5 milligram/deciliter. |
| Number of Participants With rCDI Who Had Associated Hospital Admissions | Up to 8 weeks | Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin within 8 weeks of the cessation of initial curative treatment. The number of unformed \[types 5-7 on the Bristol stool scale\] bowel movements per day were recorded by the participant in the stool diary in order to identify a new episode of diarrhea. All new episodes of diarrhea were tested for toxigenic Clostridioides difficile to confirm CDI recurrence. |
| Maximum Observed Plasma Concentration (Cmax) of REC-3964 | Pre-dose, 1 hour, 3 hours, and 6 hours post morning dose on Day 1 and Day 15 | — |
Countries
United States
Participant flow
Recruitment details
Due to early study termination, only 3 participants were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| REC-3964 250 mg Participants received REC-3964 given at a dose 250 mg q12h. | 1 |
| REC-3964 500 mg Participants received REC-3964 given at a dose of 500 mg q12h. | 1 |
| Observation Participants underwent watchful waiting. No treatment was administered. | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | — | Total |
|---|---|---|
| Age, Continuous | — years | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | — | 0 Participants |
| Race (NIH/OMB) Asian | — | 0 Participants |
| Race (NIH/OMB) Black or African American | — | 0 Participants |
| Race (NIH/OMB) More than one race | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | — | 0 Participants |
| Race (NIH/OMB) White | — | 0 Participants |
| Sex: Female, Male Female | — | 0 Participants |
| Sex: Female, Male Male | — | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 0 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Number of Participants With Related TEAEs
A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An Investigator who was qualified in medicine determined relationship to the study drug for each AE (unrelated or related). The Investigator decided whether, in his or her medical judgment, if there was a reasonable biological possibility that the event may have been caused by the study drug.
Time frame: Up to 8 weeks
Population: All randomized participants who received at least 1 dose of REC-3964 intervention or who were followed-up on in the Observation arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REC-3964 250 mg | Number of Participants With Related TEAEs | 0 Participants |
| REC-3964 500 mg | Number of Participants With Related TEAEs | 0 Participants |
| Observation | Number of Participants With Related TEAEs | 0 Participants |
Primary
Number of Participants With Serious TEAEs
A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A Serious TEAE was defined as results in death, immediately life-threatening, requires in-participant hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity in conducting activities of daily living for at least 28 days, results in a congenital abnormality or birth defect, or an important medical event that may jeopardize the participant or may require medical intervention.
Time frame: Up to 8 weeks
Population: All randomized participants who received at least 1 dose of REC-3964 intervention or who were followed-up on in the Observation arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REC-3964 250 mg | Number of Participants With Serious TEAEs | 0 Participants |
| REC-3964 500 mg | Number of Participants With Serious TEAEs | 0 Participants |
| Observation | Number of Participants With Serious TEAEs | 0 Participants |
Primary
Number of Participants With Survival Without Recurrence or Requirement for Additional Clostridioides Difficile Infection (CDI) Treatment
Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin or requirement for additional CDI treatment during the 8-week Follow-up Period after cure of preceding CDI with initial curative treatment.
Time frame: 8 weeks
Population: All randomized participants who received at least 1 dose of REC-3964 intervention or who were followed-up on in the Observational arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REC-3964 250 mg | Number of Participants With Survival Without Recurrence or Requirement for Additional Clostridioides Difficile Infection (CDI) Treatment | 1 Participants |
| REC-3964 500 mg | Number of Participants With Survival Without Recurrence or Requirement for Additional Clostridioides Difficile Infection (CDI) Treatment | 1 Participants |
| Observation | Number of Participants With Survival Without Recurrence or Requirement for Additional Clostridioides Difficile Infection (CDI) Treatment | 1 Participants |
Primary
Number of Participants With TEAEs Leading to Study Drug Discontinuation
A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Time frame: Up to 8 weeks
Population: All randomized participants who received at least 1 dose of REC-3964 intervention or who were followed-up on in the Observation arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REC-3964 250 mg | Number of Participants With TEAEs Leading to Study Drug Discontinuation | 0 Participants |
| REC-3964 500 mg | Number of Participants With TEAEs Leading to Study Drug Discontinuation | 0 Participants |
| Observation | Number of Participants With TEAEs Leading to Study Drug Discontinuation | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Time frame: Up to 8 weeks
Population: All randomized participants who received at least 1 dose of REC-3964 intervention or who were followed-up on in the Observation arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REC-3964 250 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| REC-3964 500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Observation | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
Maximum Observed Plasma Concentration (Cmax) of REC-3964
Time frame: Pre-dose, 1 hour, 3 hours, and 6 hours post morning dose on Day 1 and Day 15
Population: Data for this outcome measure was not summarized since there was only 1 participant in each treatment arm.
Secondary
Number of Participants With rCDI Who Had Associated Hospital Admissions
Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin within 8 weeks of the cessation of initial curative treatment. The number of unformed \[types 5-7 on the Bristol stool scale\] bowel movements per day were recorded by the participant in the stool diary in order to identify a new episode of diarrhea. All new episodes of diarrhea were tested for toxigenic Clostridioides difficile to confirm CDI recurrence.
Time frame: Up to 8 weeks
Population: Data for this outcome measure was not assessed since no recurrence events occurred.
Secondary
Number of Participants With Severe rCDI
Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin within 8 weeks of the cessation of initial curative treatment. The number of unformed \[types 5-7 on the Bristol stool scale\] bowel movements per day were recorded by the participant in the stool diary in order to identify a new episode of diarrhea. All new episodes of diarrhea were tested for toxigenic Clostridioides difficile to confirm CDI recurrence. Severe CDI was defined as CDI with white blood cell count \>15,000 cells/milliliter and/or serum creatinine ≥1.5 milligram/deciliter.
Time frame: Up to 8 weeks
Population: Data for this outcome measure was not assessed since no recurrence events occurred.
Secondary
Rate of Recurrent Clostridioides Difficile Infection (rCDI)
Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin within 8 weeks of the cessation of initial curative treatment. The number of unformed \[types 5-7 on the Bristol stool scale\] bowel movements per day were recorded by the participant in the stool diary in order to identify a new episode of diarrhea. All new episodes of diarrhea were tested for toxigenic Clostridioides difficile to confirm CDI recurrence. The rate of rCDI was defined as the proportion of participants who had the Clostridioides difficile recurrence among randomized participants.
Time frame: 8 weeks
Population: Data for this outcome measure was not summarized since there was only 1 participant in each treatment arm.
Secondary
Time to Maximum Plasma Concentration (Tmax) of REC-3964
Time frame: Pre-dose, 1 hour, 3 hours, and 6 hours post morning dose on the Day 1 and Day 15
Population: Data for this outcome measure was not summarized since there was only 1 participant in each treatment arm.
Secondary
Time to Recurrence of rCDI
Recurrent CDI was defined as a new episode of CDI associated with a new positive Clostridioides difficile stool toxin within 8 weeks of the cessation of initial curative treatment. The number of unformed \[types 5-7 on the Bristol stool scale\] bowel movements per day were recorded by the participant in the stool diary in order to identify a new episode of diarrhea. All new episodes of diarrhea were tested for toxigenic Clostridioides difficile to confirm CDI recurrence. Time to recurrence of rCDI was to be assessed using Kaplan-Meier estimation.
Time frame: Up to 8 weeks
Population: Data for this outcome measure could not be estimated since no recurrence events occurred during this study.
Secondary
Trough Plasma Concentration (Ctrough) of REC-3964
Time frame: Pre-dose on Day 15
Population: Data for this outcome measure was not summarized since there was only 1 participant in each treatment arm.