Assessing the Safety, Immune Response, and Early Efficacy of a Candida Vaccine in Women with Recurrent Vulvovaginal Candidiasis: A Randomized Controlled Study

Temporary halt TH-17891

Halt date

2024-03-06

Member states concerned

Belgium

Publication date

2024-03-20

Reason

Medicinal Product related

Explanation

During the ongoing stability study at T = 9 months, the “Visual Particles Inspection” method for the Candi5V IMP resulted in an out of specification for the samples stored at long term storage condition of –20 ± 5°C. In 2 out of 15 vials one visible particle with approximately <0.2 mm was observed on the Candi5V01 IMP. This result does not comply with the specification criteria for the Candi5V IMP, which is defined as “essentially free of visible particles”. Due to this OOS and until this is resolved we have temporarily halted the clinical trial.

Follow-up measures

The trial is currently at “step 1” and only one clinical site, in Belgium, is active. Vaccinations have been paused on 06.03.2024 immediately after becoming aware of the out of specification described above. The Candi5V IMP has been also quarantined on the site.
At the time of the halt, all participants of the first group had received their first vaccination (6 vaccine:2 placebo) and no additional groups had been enrolled. All participants from group 1 have performed the safety follow up visit 7-days after vaccination (V3). In addition, 6 participants had completed the 14-days follow-up visit (V4), and 4 completed the 1-month follow-up visit (V5). From the data analyzed , no safety issues have been identified, no holding rules have been met and no Severe (Grade 3 or 4) AEs, SAEs or SUSARs have been reported until now (AE listing is attached as a separate document). During this temporary halt of the trial, all participants will be kept in the study and continue with all study procedures except those associated to the 2nd vaccination (no 2nd vaccination and no visit 7 days after 2nd vaccination). Enrolment of Group 2 will occur as per protocol and is planned to start after the restart of the trial.

A plan currently is being established to investigate this OOS and the impact it has on the quality of the product. The plan includes the following actions:
- Formal confirmation of the OOS in the Analytical Laboratory performing the visual particles inspection.
- Completion of all stability indicating tests at T = 9months.
- Confirm that removal of the particles results in a product with an antigen content that is within the variability of the analytical content estimation.
- Assessment of the compatibility of the drug product formulation with filter needles for the removal of particles for continuation of the clinical trial. Confirmation of compatibility of the filter needles with the drug product and update of the IMPD as follows:
o Specification for the visual inspection test will be adjusted to allow the presence of visible particles. The justification will be that filter needles used during preparation of the drug product at the clinical trial site will remove any particle present before injection.
o All other specifications will remain unchanged.
o Additionally, the IMPD will be updated with the compatibility study performed on the filter needles (which means that no changes in the concentrations of the antigens will be shown post filtering at different storage temperatures) and with the latest stability data from ongoing stability studies.
o A “substantial modification” will be filed with the regulatory authority.

Benefit-risk balance changed

No

Treatment stopped

Yes