Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06367361 |
| Other study ID # |
SIDISI 201221 |
| Secondary ID |
U01AI155323 |
| Status |
Not yet recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
July 2024 |
| Est. completion date |
March 2028 |
Study information
| Verified date |
April 2024 |
| Source |
Universidad Peruana Cayetano Heredia |
| Contact |
Miguel M Cabada, MD MSc |
| Phone |
+1 409 747 0236 |
| Email |
micabada[@]utmb.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Randomized clinical trial comparing the efficacy and safety of oxfendazole at 20 mg/kg per
dose in one and two dose regimens with a two-dose regimen of triclabendazole at 10 mg/kg in
an endemic region of the highlands of Peru. Children and adults with fascioliasis in rural
communities will be screened for inclusion and exclusion criteria and a total of 336 subjects
(112 per study arm) with chronic Fasciola infection will be enrolled and assigned randomly to
the study arms in a 1:1:1 ratio. The primary efficacy (cure and egg reduction) endpoints will
be assessed on day 7 and 30 post treatment. The secondary safety endpoint visits will be
performed in days 0, 3, 7 and 30 post-treatment and Population PK modeling studies will be
performed in the first 24 hours after the first dose of oxfendazole.
Description:
Quality Control and Quality Assurance Following a written DSMB-accepted site quality
management plan, the participating site and the subcontractors will be responsible for
conducting routine quality assurance and quality control activities to internally monitor
study progress and protocol compliance. The site principal investigator will provide direct
access to all study-related sites, source data/data collection forms, and reports for the
purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory
authorities.
The site principal investigator will ensure all study personnel are appropriately trained and
applicable documentations are maintained on site. The study principal investigator is the
person primarily responsible for assuring compliance. The study principal investigator will
regularly review the study progress with team members and conduct periodic audits to ensure
that informed consent has been obtained and documented. The principal investigator will
review the team operations and progress to ensure that study records are up to date,
complete, and kept in a secure place accessible only to appropriate study personnel.
Data Handling and Record Keeping The investigator is responsible to ensure the accuracy,
completeness, legibility, and timeliness of the data reported. All source documents will be
completed in a neat, legible manner to ensure accurate interpretation of data.
Data collection forms will be derived from the CRFs and provided to the study site to record
and maintain the data for each subject enrolled in the study. Data reported in the CRF
derived from source documents will be consistent with the source documents or the
discrepancies will be explained.
The data collection is the responsibility of the clinical trial staff at the site under the
supervision of the site principal investigator. The investigator will maintain complete and
accurate documentation for the trial. All source documents and laboratory reports will be
reviewed by the clinical team and data entry staff to ensure the accuracy and completeness.
AEs will be graded, assessed for severity and causality, and reviewed by the site principal
investigator or a designee.
Data Capture Methods Clinical data (including AEs and ConMeds) and clinical laboratory data
will be entered into a pre-designed eCFR on REDCap. The clinical data will be entered
directly from the source documents. The CRF can be considered as a source document.
the access to the REDCap platform will be strictly limited to study staff. The level of
access and capabilities for creating new records and changing existing records will be
assigned according to specific staff work and need. For example, laboratory staff will only
have access to the CRF for reporting test results and not to the CRFs where the intervention
arm or assigned drug is documented. Laboratory staff will not be able to make changes to any
forms except the results form. REDCap's log-in trail will allow the principal investigator to
track access to the platform and the changes made to the record during the time logged-in.
The platform will be strictly password protected and limited to designated trial personnel.
Subjects will be assigned a unique identifier. All subject's records or data sets transferred
to the sponsor will contain the identifier only. Subject's names or information that would
identify the subject will not be transferred. Quality control will be performed as outlined
in Chapter 13 of the protocol. The quality control procedures will be specified in the MOP
and CRF guidance.
Types of Data The data for this trial will include clinical, demographic, safety, hematology
and chemistry laboratory values, neuroimaging (MRI) and results of stool egg counts.
Timing/Reports Safety data will be reviewed by the DSMB per the DSMB charter for this trial.
The DSMB will review available safety data. Interim statistical reports may be generated as
deemed necessary and appropriate by DMID.
Subjects found to have intestinal parasites in the final stool examination will be contacted
and referred to a local health provider to receive standard of care therapy at no cost.
Study Records Retention Study records and reports including, but not limited to, CRFs, source
documents, ICFs, laboratory test results, and study drug disposition records will be retained
for at least 2 years after a marketing application is approved for the study product to treat
fascioliasis. If no application is filed or if the application is not approved for the study
product, records will be retained until 2 years after the investigation is discontinued and
the FDA has been notified. The documents will be retained for a longer period if required by
local regulations. ICFs for future use will be maintained as long as the sample/specimen
exists.
No records will be destroyed without the written consent of the sponsor. It is the
responsibility of the sponsor to inform the site principal investigator when these documents
no longer need to be retained.
Sample Size Considerations The primary outcome for the study will be the parasitological cure
rate of chronic fascioliasis assessed by the qualitative (yes/no) results of the Kato Katz
and Lumbreras Rapid Sedimentation stool tests on Visit Day 30. A subject will be considered
cured if the result is negative (0 eggs/gr of stool) at 30 days after treatment. Thus, a
binomial response (BR) will be obtained where: If stool microscopy = 0 on Day 30, then BR =
1; otherwise, BR = 0.
The primary analysis will consist of the statistical comparisons between binomial proportions
for the single dose OXF arm versus the TCBZ arm and the two dose OXF arm versus the TCBZ arm
using the Chi square test statistic with an alpha = 5%. Assuming a cure rate of at least 90%
for the single OXF dose arm and at least 90% in the TCBZ arm a sample size of n= 112 per
group will be able to exclude an effectiveness difference of > 10% in favor of the TCBZ
treatment with 80% power and a difference at five percent level of significance. Similarly,
assuming the same effectiveness (at least 90%) for the double OXF dose arm and the TCBZ arm,
a sample size of n= 112 per group will be able to exclude an effectiveness difference of >
10% in favor of the TCBZ treatment with 85% power and a difference at five percent level of
significance.
Final Analysis Plan The efficacy analysis will be performed in a modified Intention-To-Treat
approach. All subjects who were randomized in the study and receive at least one dose of
study medication will be considered evaluable and entered in the final analysis database.
Subjects in this population will be analyzed according to the group to which they were
originally randomized. The same criteria to define the population will be used for the safety
analysis. Subjects who do not complete outcome assessments will be considered treatment
failures regardless of their randomization group and final status.
Initially, the distribution of baseline population characteristics collected in visit day 1
will be summarized according to the randomization arms using frequencies, means (±SD),
medians (interquartile range), and ranges. The characteristics of the groups will be compared
using Chi square tests for categorical variables and the T-test (ANOVA if indicated) for the
continuous variables. The primary efficacy endpoint will be summarized as the percent of
subjects with parasitological cure in each arm at visit day 30. The efficacy between groups
will be compared using a Chi Square test with a p ≤ 0.05 to determine the significance off
the differences. The efficacy analyses will also be performed using generalized linear
regression models to assess any possibility of effect modification and to adjust for any
population (study strata/province) and parasitological characteristic that may appeared to be
unbalanced after randomization. The egg reduction end point will be analyzed calculating the
mean (or median if indicated) egg reduction for the treatment groups and comparing them using
the T-Test (or Mann-Whitney test if indicated). Similarly, the egg reduction tests results
will be modeled using multiple generalized linear regression to account for imbalances
between the groups. Finally, the absolute frequency of all AEs and specifically SAEs will be
compared post-treatment versus baseline using Poisson models for count data to determine
potential safety concerns. The proportion of individuals with SAEs will be also calculated
and compared between arms. A detailed Analysis Plan will be submitted to the Study DSMB for
approval before any study activities are initiated.
