Study of Debio 1450 for Bacterial Skin Infections

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of 2 different doses of intravenous and oral Debio 1450 compared with intravenous vancomycin and oral linezolid in the treatment of patients with staphylococcal ABSSSI.

Official Title
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A Phase 2, Randomized, Double-Blind, Multicenter Study of Safety, Tolerability, and Efficacy of Debio 1450 vs Vancomycin (IV)/Linezolid (Oral) in the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) Due to Staphylococcus Sensitive or Resistant to Methicillin

Conditions
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Bacterial Infections

Intervention / Treatment
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* Drug: Debio 1450 IV
* Drug: Debio 1450 Oral
* Drug: Linezolid
* Drug: Debio 1450 Oral Placebo
* Drug: Linezolid Placebo
* Drug: Vancomycin IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has clinically documented infection of the skin or skin structure suspected or documented to be caused by a staphylococcal pathogen Meets other protocol-specified criteria for qualification and contraception Is willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related to food, drink and medications Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures Exclusion Criteria: Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: the safety or well-being of the participant or study staff; the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding); the analysis of results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Debio 1450 320/480 mg<br>After 2 doses of Debio 1450 IV (intravenous) therapy, the Debio 1450 320/480 mg daily dose group receives 240 mg Debio 1450 Oral + Linezolid Placebo twice daily (BID). | Drug: Debio 1450 IV<br>* Intravenous (IV) form of Debio 1450 will be supplied in vials containing 50 mg of active pharmaceutical ingredient (API). Intravenous infusions of Debio 1450 (160 mg and 80 mg) will be administered over a 2-hour period BID every 12 hours within a 2-hour window (12 ± 2 hours).<br>Drug: Debio 1450 Oral<br>* Oral forms of Debio 1450 will be provided as white, opaque, hard gelatin capsules containing 50 mg drug substance (equivalent to 40 mg of Debio 1450).<br>Drug: Linezolid Placebo<br>* Linezolid placebo will be supplied as film-coated compressed tablets.<br>|
| Experimental: Debio 1450 160/240 mg<br>After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group receives 120 mg Debio 1450 Oral + Debio 1450 Oral Placebo + Linezolid Placebo BID. | Drug: Debio 1450 IV<br>* Intravenous (IV) form of Debio 1450 will be supplied in vials containing 50 mg of active pharmaceutical ingredient (API). Intravenous infusions of Debio 1450 (160 mg and 80 mg) will be administered over a 2-hour period BID every 12 hours within a 2-hour window (12 ± 2 hours).<br>Drug: Debio 1450 Oral<br>* Oral forms of Debio 1450 will be provided as white, opaque, hard gelatin capsules containing 50 mg drug substance (equivalent to 40 mg of Debio 1450).<br>Drug: Debio 1450 Oral Placebo<br>* Debio 1450 placebo will be supplied as white, opaque, hard gelatin capsules.<br>Drug: Linezolid Placebo<br>* Linezolid placebo will be supplied as film-coated compressed tablets.<br>|
| Placebo Comparator: Placebo<br>After 2 doses of Vancomycin IV, the Placebo comparator group receives Debio 1450 Oral Placebo + Linezolid 600 mg BID. | Drug: Linezolid<br>* Linezolid for oral administration will be provided as 600-mg film-coated compressed tablets.<br>Drug: Debio 1450 Oral Placebo<br>* Debio 1450 placebo will be supplied as white, opaque, hard gelatin capsules.<br>Drug: Vancomycin IV<br>* Vancomycin will be administered BID every 12 ± 2 hours at doses of 1 g or 15 mg/kg as specified in local protocols, with the infusion rate adjusted to 2 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Clinical Response Rate (ECRR): Percentage of Responders to Treatment at 48 to 72 Hours From Randomization as Assessed by the Investigator | ECRR was defined as the percentage of responders to treatment at 48 to 72 hours from randomization. Responders were the participants who showed greater than or equal to (≥) 20% reduction in area of the primary lesion involving erythema, edema, or induration of the primary ABSSSI lesion (as assessed by the ruler method) at 48 to 72 hours compared to baseline. | At 48 to 72 hours from randomization (Day 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Success Rate: Percentage of Participants Assessed by the Investigator as Responders at 48 to 72 Hours From Randomization, at End of Treatment (EOT) and Short-term Follow-up (STFU) | The Investigator Assessment of Clinical Outcome (IACO) of treatment was assessed for each participant as success or failure at 48 to 72 hours after randomization at EOT and STFU visits. Clinical success was resolution or near resolution of most disease-specific signs and symptoms and no new signs, symptoms, or complications attributable to ABSSSI such that no further antibiotic therapy is required for treatment of original site of infection. Clinical failure was requirement for additional antibiotic therapy for treatment of the original site of infection or incision and drainage of ABSSSI site that was not both anticipated and completed within a 48- to 72-hour window following randomization, or unplanned major surgical intervention required due to failure of study medication or development of osteomyelitis after baseline. Participants who met both success criteria and none of failure criteria were considered as a clinical success for IACO. | 48 to 72 hours after randomization (Day 4), EOT (Day 12) and STFU (Day 19) | 
| Clinical Success Rate: Percentage of Participants Assessed by the Sponsor as Responders After 7 to 10 Days of Treatment at EOT and STFU | The Sponsor's Assessment of Clinical Outcome was obtained at EOT and STFU visits based on IACO and additional criteria. Sponsor assessed participants as clinical failure if they required non-study or rescue antibiotics due to lack of efficacy after at least 48 hours from randomization or experienced drug-related serious adverse events (SAEs) or discontinuation of study medication for drug-related AEs or required antibiotic therapy for longer than 10 days or had the need for unplanned surgical intervention >48 hours after randomization. As per IACO, clinical success was resolution or near resolution of most disease-specific signs and symptoms and no new signs, symptoms or complications. Clinical failure was requirement for additional antibiotic therapy or incision and drainage of ABSSSI site or unplanned major surgical intervention or development of osteomyelitis. | EOT (Day 12) and STFU (Day 19) | 
| Percentage of Participants With a Composite Assessment of Clinical Outcome (CACO) of Success | CACO of treatment was determined as a combined outcome of early response to treatment (at 48 to 72 hours from randomization) and IACO at the STFU visit. Participants had a CACO of success if they met both of the following criteria: An early response to treatment (at 48 to 72 hours from randomization) (ECR = responder) and a clinical outcome of success at the STFU visit (7 to 14 days after EOT) based on IACO (IACO = success). | 48 to 72 hours after randomization (Day 4) and STFU (Day 19) | 
| Percentage of Participants Who Showed Microbiological Evidence of Cure 48 to 72 Hours From Randomization, EOT, and STFU | The microbiological outcome was assessed by the sponsor at 48 to 72 hours from randomization, EOT and STFU. It was based on blood and skin lesion identification results from baseline samples and skin lesion identification results from baseline samples and skin lesion identification results from follow-up samples as well as on, molecular typing results, and the IACO. Microbiological eradication rate was defined as proportion of participants with 'Documented Eradication' (absence of baseline pathogen(s) in follow-up cultures of the original site of infection.) or 'Presumed Eradication' (no material available for culture and an IACO of 'Success') in relation to the total number of participants in the respective treatment group. | 48 to 72 hours after randomization (Day 4), EOT (Day 12) and STFU (Day 19) |