Methotrexate PK (in combination with Novobiocin) in RA patients

Temporary halt TH-136307

Halt date

2026-05-22

Planned restart

2026-09-01

Member states concerned

Netherlands

Publication date

2026-05-28

Reason

Sponsor decision

Explanation

An additional interim analysis is scheduled to evaluate the PK and safety data of all patients that completed the study up to now (N=12). The primary reason for the additional interim analysis is the observation of mild injection site reactions following novobiocin administration, with symptoms including swelling, tenderness and erythema. Although these reactions resolved within one week and were less pronounced in patients receiving 80 mg novobiocin (N=4) compared with those receiving 150 mg (N=4) or 200 mg (N=4), reactions were still observed in 2 out of 4 patients in the 80 mg group.

The PK analysis will provide further insight into whether the novobiocin dose should be increased or can be decreased further compared to the 80 mg dose. Based on the PK results of the patients receiving 200 mg (N=4), a lower dose of 50 mg novobiocin was predicted to maintain exposure above IC90 for approximately 12 hours. The additional PK analysis of patients receiving 150 and 80 mg novobiocin will be used to determine whether dose adjustments (either escalation or reduction) are required and whether any additional protocol modifications are needed to optimize the study design for the remaining 4 patients to be enrolled.

Follow-up measures

All patients enrolled in the study (N=12) have completed the EOS visit. Two patients who were scheduled for Day 1 dosing on 16 June had their appointments cancelled. In addition, patients who were scheduled for screening were informed on the decision and their appointments were also cancelled.

A substantial amendment reflecting the decisions made following the interim analysis will be submitted prior to study continuation.

Benefit-risk balance changed

No

Treatment stopped

Yes