This is a single-center, single-arm, open label, non-randomized, fixed dose-escalation, phase 1 study, performed in ambulatory and day-hospital setting. After a screening period, patients will enter a drug administration period, followed by a 'post-study' period.
Four IMP321 dose levels, 50 µg, 250 µg, 1.250 mg, 6.250 mg and 30 mg will be evaluated in successive cohorts of patients. At any given dose level 3 patients will be administered one subcutaneous dose every 2 weeks for a total of 12 weeks (6 injections in total), separated by 13-day administration-free intervals.
The next (higher) dose level will be dosed to 3 new patients if the previous dose level has been well tolerated. Investigator will decide whether the safety is acceptable by performing an evaluation after the third administration (at week 8) and if the next patients can be included.
The successive cohorts of patients are summarized as follows:
* Cohort A will correspond to a group of 3 patients receiving the 50 µg dose. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration, the following cohort will be undertaken.
* Cohort B will correspond to a group of 3 patients receiving the 250 µg dose. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration, the following cohort will be undertaken.
* Cohort C will correspond to a group of 3 patients receiving the 1,250 µg dose. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration, the following cohort will be undertaken.
* Cohort D will correspond to a group of 3 patients receiving the 1,250 µg dose. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration, the following cohort will be undertaken.
* Cohort E will correspond to a group of 3 patients receiving the 6,250 µg dose. The patients will receive their first administration one-by-one with a two-weeks interval. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration for the last patient, the following cohort will be undertaken.
* Cohort F will correspond to a group of 3 patients receiving the 6,250 µg dose. If the tolerability of this dose level has been judged acceptable in cohort E, the three patients will receive their first IMP321 injection simultaneously.
* Cohort G will correspond to a group of 3 patients receiving the 30,000 µg dose. The patients will receive their first IMP321 administration one-by-one with a two-weeks interval (+/- 5 days). If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration for the last patient, the following cohort will be undertaken.
* Cohort H will correspond to a group of 3 patients receiving the 30,000 µg dose. If the tolerability of this dose level has been judged acceptable in cohort E, the three patients will receive their first IMP321 injection simultaneously.
Once the main period of study has been completed, namely two weeks after a cohort is completed, i.e. at week 14, all patients will undergo an ambulatory 'post-study' examination.
Patients of the Cohort B, C, E, F and G will participate in a pharmacokinetic (PK) study and all patients in a pharmacodynamic (PD) study involving additional blood samples.
