StaphAcute

4.7.1    Primary outcomes and target variables

Phase I:

•           The incidence of AEs and SAEs after a single i.v. infusion of IMP including clinically significant laboratory abnormalities and AESIs (infusion/antibody-related reactions: allergic reactions, anaphylaxis, cytokine release syndrome).

Phase IIa:

•           The incidence of AEs and SAEs after a single i.v. infusion of IMP including clinically significant laboratory abnormalities and AESIs (infusion/antibody-related reactions: allergic reactions, anaphylaxis, cytokine release syndrome).

 

Phase IIa:

•           Patients of any sex.

•           Age ≥ 18 years.

•           Blood culture positive for S. aureus within 72 hours before screening.

•           At the time of taking blood culture the patients must show at least two of the following symptoms or signs:

         Shortness of breath

         Sweating

         Fatigue

         Pain associated with metastatic foci

         Fever (oral temperature equivalent ≥ 38°C)

         Leukocytosis (white blood cell [WBC] count > Upper Limit of Normal [ULN]), leukopenia (WBC < Lower Limit of Normal [LLN]), or bandemia (> 10% immature neutrophils regardless of total peripheral WBC)

         Tachycardia (heart rate > 100 bpm)

         Tachypnea (respiratory rate > 20 breaths/min)

         Hypotension (systolic blood pressure < 90 mmHg).

•           Signed IC.

•           Willing to practice highly effective contraception (Section 4.4.2.1) during the trial period or evidence of non-existent reproductive potential.

Phase I:

•           Pregnancy or breastfeeding.

•           Relevant acute or chronic illness, relevant abnormalities of clinical laboratory tests or ECG.

•           Known hypersensitivity to any constituent of the IMP.

•           Participation in another clinical trial with an IMP within the past 12 weeks or expected participation during this trial.

•           Dependency on the PI or trial staff; or site personnel directly affiliated with this trial.

•           Legally incapacitated individuals.

•           Individuals held in an institution by legal or official order.

•           If engaging in sexual activity that could result in pregnancy, inability or unwillingness to comply with the requirements for highly effective contraception.

Phase IIa:

•           Patient who previously received StaphAcute.

•           Treatment with dalbavancin or oritavancin for the current infection. Patients who are receiving teicoplanin, linezolid, telavancin, ceftaroline, fosamil, clindamycin, and/or sulfamethoxazole/trimethoprim are eligible for the trial, provided that treatment is switched to an appropriate i.v. SOC antibacterial agent (SOC agents include semi-synthetic penicillins [e.g., nafcillin, oxacillin, cloxacillin, flucloxacillin] or first-generation cephalosporins [e.g., cefazolin] for MSSA and daptomycin and vancomycin for MRSA).

•           Patient whose MSSA/MRSA infection is not treated with the intent to cure.

•           Patient participated or plans to participate in an interventional investigational drug, device, or diagnostic trial within 30 days or 5 half-lives of investigational drug, whichever is longer, prior to or during the trial.

•           Any condition that would, in the opinion of the investigator, pose a safety risk or impairs patient’s ability to complete the trial.

•           Pregnancy or breastfeeding.

•           Patient is employed by the Sponsor or investigational site or is a first degree relative of a person employed by the Sponsor or investigational site.

•           Patient is institutionalized by administrative or court order.

•           Legally incapacitated individuals.

•           If engaging in sexual activity that could result in pregnancy, inability or unwillingness to comply with the requirements for highly effective contraception.

StaphAcute will be administered as single i.v. infusion.

Phase I:

StaphAcute will be administered at escalating doses of 1, 5, 10, or 20 mg/kg BW depending on consecutive cohort allocation.

Phase IIa:

The MTD of StaphAcute determined in the Phase I will be administered to SAB patients in addition to SOC.

StaphAcute will be provided as a sterile injectable solution in

10 mL vials. Each vial will contain 5.3 mL of StaphAcute

(10 mg/mL). StaphAcute will be filled into infusion bags (or syringes) as specified in the Pharmacy Manual and administered as a single i.v. infusion as described in the Phase I and Phase IIa Trial Manuals.

 

Sterile normal saline (NaCl 0.9%) will be used as placebo comparator in Phase IIa and administered as a single i.v. infusion in addition to SOC.

For participants assigned to receive placebo, an infusion bag (or syringe) containing sterile normal saline at the nominal volume that would be provided for weight-adjusted StaphAcute will be prepared.

Placebo will be administered as specified in the Pharmacy Manual and administered as a single i.v. infusion as described in the Phase I and Phase IIa Trial Manuals.