A Phase Ⅱ Clinical Study of 9MW1411 Injection in Acute Bacterial Skin and Skin Structure Infections

NCT05339802 | Unknown Phase 2

• 1 other identifier: 9MW1411-2021-CP201
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, a multicenter, randomized, double-blind, placebo-controlled trial design is used to evaluate the efficacy and safety of two doses of 9MW1411 injection in patients with ABSSSI caused by S. aureus. The Recommended Phase 2 Dose (RP2D) of 9MW1411 injection for this placebo-controlled study is comprehensively selected based on the results of Phase I clinical trials and preclinical PK/PD analysis. Approximately 90 subjects with ABSSSI caused by S. aureus are planned to be enrolled, and the infection type and presence or absence of single S. aureus infection will be used as randomization stratification factors for all randomized subjects. They are randomized in a 1: 1: 1 ratio.

Conditions

Skin Infection

Outcome Measures

Primary Outcomes (5)

• Clinical cure in the mITT Population at the Test of cure (TOC) Visit

  Evaluate the Efficacy of 9MW1411

  TOC:Test of cure; 14 days after the last day of linezolid therapy.

• Incidence and severity of adverse events (AEs)，serious adverse event (SAEs)

  Evaluate the Safety of 9MW1411

  From day 1 to day 57（±7） after administration

• Incidence of abnormal clinical laboratory findings in 12-lead ECG parameters, vital signs, physical examination

  Evaluate the Safety of 9MW1411

  Screening (within 48 hours prior to the first dose of test article) to Follow-up (Day 57±7)

• Maximum Observed Concentration (Cmax)

  Evaluate the pharmacokinetics profile of 9MW1411

  From day 1 to day 57（±7） after administration

• Incidence of anti-drug antibodies

  Evaluate the immunogenicity of 9MW1411

  From day 1 to day 57（±7） after administration

Secondary Outcomes (1)

• Eearly clinical response at 48h~72h after first dose of 9MW1411

  48h~72h after first dose of 9MW1411

Other Outcomes (1)

• Linezolid Trough Concentration

  Before the day of administration, 3 days after administration, 7 days after administration

Study Arms (3)

Cohort 1

EXPERIMENTAL

9MW1411 injection , single administration, intravenous infusion, infusion time 2H (120 ± 15min);

Combination Product: 9MW1411 injection 1 combined with Linezolid

Cohort 2

EXPERIMENTAL

9MW1411 injection , single administration, intravenous infusion, infusion time 2H (120 ± 15min);

Combination Product: 9MW1411 injection 2 combined with Linezolid

Placebo

PLACEBO COMPARATOR

9MW1411 injection placebo, single administration, intravenous infusion, infusion time: 2h (120 ± 15min)

Combination Product: 9MW1411 injection placebo combined with Linezolid

Interventions

9MW1411 injection 1 combined with Linezolid COMBINATION_PRODUCT

After randomization, 9MW1411 injection, single dose, intravenous infusion, linezolid: 600mg, given intravenously or orally every 12 hours, for a total course of treatment not exceeding 14 days.

Cohort 1

9MW1411 injection 2 combined with Linezolid COMBINATION_PRODUCT

After randomization, 9MW1411 injection, single dose, intravenous infusion, linezolid: 600mg, given intravenously or orally every 12 hours, for a total course of treatment not exceeding 14 days.

Cohort 2

9MW1411 injection placebo combined with Linezolid COMBINATION_PRODUCT

After randomization, 9MW1411 injection placebo, single dose, intravenous infusion, linezolid: 600mg, given intravenously or orally every 12 hours, for a total course of treatment not exceeding 14 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18 to 75 years (including 18 and 75 years);
• One of the following types of skin and skin structure infection is met:
• Cellulitis: A diffuse skin infectious disease characterized by diffuse congestion (erythema), edema and/or induration within 7 days of the Screening Visit. The lesion area is at least 75 cm2, calculated as the longest diameter (along the head-to-foot of the human body) multiplied by the widest diameter (perpendicular to the longest diameter), which are measured by the investigator with a ruler.
• Wound infection: An infectious disease characterized by purulent drainage from a wound or surgical wound, periwound congestion (erythema), edema and/or induration within 7 days of the Screening Visit. The shortest diameter measured from the perimeter of the wound is at least 5 cm and the lesion area is at least 75 cm2, calculated as the longest diameter (along the head-to-foot of the human body) multiplied by the widest diameter (perpendicular to the longest diameter), which are measured by the investigator with a ruler.
• Large cutaneous abscess: An infectious disease characterized by congestion (erythema), edema, and/or induration with collection of pus in the dermis or deeper for the first time within 7 days of the Screening Visit. The shortest diameter measured from the periphery of the abscess is at least 5 cm and the lesion area is at least 75 cm2, calculated as the longest diameter (along the head-to-foot of the human body) multiplied by the widest diameter (perpendicular to the longest diameter), which are measured by the investigator with a ruler.
• Burn infection: An infectious disease characterized by purulent drainage with congestion (erythema), edema and/or induration. The shortest diameter measured from the periphery of the burn infection is at least 5 cm and the lesion area is at least 75 cm2 (burn depth is Grade II or higher), calculated as the longest diameter (along the head-to-foot) multiplied by the widest diameter (perpendicular to the longest diameter), which are measured by the investigator with a ruler. Burns occur within 7 days prior to the Screening Visit and cover 10% to 50% of their total body surface area. Patients with burn infections do not exceed 20% of all subjects.
• Diabetic foot infection: The subject meets diagnostic criteria for type 1 or 2 diabetes and meets the Infectious Diseases Society of America/International Working Group on Diabetic Foot (IDSA/IWGDF) criteria for moderate infection of diabetic foot (Appendix 1): patients with infection have good systemic function and stable metabolism. However, the patient has ≥ 1 of the following characteristics: ①cellulitis extending \> 2 cm around the ulcer, ② lymphatic stripes, ③spreading beneath the superficial fascia, ④deep tissue abscesses; The subject meets the diagnostic criteria for diabetic foot and Wagner grade 2 (Appendix 2) that the ulcer lesion time \< 4 weeks: ①If multiple ulcer lesions are present at the same time, the largest lesion is selected as the observed lesion; ②The ulcer lesion is measurable and the lesion area is ≥ 5 cm2, which is calculated as the longest diameter (along the head-foot of the human body) multiplied by the widest diameter (perpendicular to the longest diameter), which are measured by the investigator with a ruler. Patients with diabetic foot infection do not exceed 10% of all subjects.
• Subjects must have at least two of the following signs/symptoms:
• Drainage or discharge of pus;
• Erythema;
• Fluctuation sensation;
• Increased skin temperature;
• Edema or induration;
• Tenderness;
• Patients with systemic reactions that meet any of the following:

You may not qualify if:

• Patients with uncomplicated skin and skin structure infections, such as furuncles, minor abscesses (no cellulitis/erysipelas around the suppurative area), pustular lesions, superficial or localized cellulitis/erysipelas, and small wound infections (eg, suture abscesses).
• Patients with confirmed or suspected acute infection of skin and skin structures caused solely by gram-negative bacteria or anaerobes, fungi, and parasites.
• Presence of any of the following infections:
• Patients with confirmed or suspected osteomyelitis; Patients with confirmed or suspected suppurative arthritis; Patients with implant devices that cannot be removed at the site of infection, such as artificial joints, intravascular catheters, and batteries of permanent pacemakers, etc.; Patients with previous chronic dermatitis or other chronic inflammatory skin lesions, such as eczema and psoriasis, which may affect the judgement of their treatment response; Patients with pressure ulcer infection; Patients with life-threatening infections or infections requiring emergency surgery, such as necrotizing fasciitis, progressive gangrene, and endocarditis, etc.; Patients with infection after human or animal bites (except arthropods).
• Evidence of any of the following serious immune system disorders:
• Patients with current or expected neutropenia reducing, defined as neutrophil count \< 1.5 x 109/L; Patients received cancer chemotherapy, radiotherapy, or strong non-corticosteroid immunosuppressive drugs (e.g., cyclosporine, azathioprine, tacrolimus, immunomodulatory monoclonal antibody therapy, etc.) within the past 3 months; Patients received prednisone at a dose of ≥ 20 mg/day for more than 14 days or an estimated course of treatment more than 14 days prior to enrollment.
• Patients with known or clinically suspected one or more of the following: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is 3 times higher than the upper limit of normal (ULN); total bilirubin is 2 times higher than the ULN, or evidence of end-stage liver disease (eg, ascites, hepatic encephalopathy).
• Patients with history or evidence of severe renal disease, or known creatinine clearance (CrCl) \< 50 mL/min (estimated using the Cockcroft-Gault formula), or requiring peritoneal dialysis, plasma exchange, hemodialysis, veno-venous dialysis, or other forms of renal filtration.
• Patients with active or history of autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, etc.) that may relapse, or patients who are at high risks (e.g., organ transplant requiring immunosuppressive therapy).
• Patients with uncontrolled or uncontrollable hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg), pheochromocytoma, carcinoid syndrome, or hyperthyroidism.
• Patients with serious or life-threatening condition or organ/system disorders (eg, endocarditis, meningitis, unstable central nervous system disorder, acidosis, or history of lactic acidosis).
• Patients with burn infection have any of the following: ①Patients with burns of special causes, such as electrical injury, chemical burns, or burns combined with compound injuries (except for arc burns); ②Patients with moderate to severe inhalation injury, severe combined injures, acute respiratory distress syndrome, multiple organ failure, disseminated intravascular coagulation, or acute cardiac insufficiency.
• Patients with diabetic foot have any of the following: ①Patients with uncontrolled blood glucose (fasting blood glucose \> 10 mmol/L) and all types of diabetic coma; ②Patients with canceration at the ulcer site; ③Patients with vascular hypoperfusion of the affected limb, ankle-brachial index (ABI) \< 0.6, requiring angioplasty; ④Patients with wound infection with gangrene, which cannot be appropriately cleared by debridement; ⑤The investigator believes that it is likely that a lower knee amputation is necessary.
• The investigator believes that the subject had any underlying medical conditions affecting participation in the study, including serious heart disease, malignancy, psychosis, ongoing treatment for epilepsy, or a history of untreated epilepsy.

Sponsors & Collaborators

• Mabwell (Shanghai) Bioscience Co., Ltd.: lead

Study Sites (1)

Huashan Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, 20040, China

RECRUITING

MeSH Terms

Conditions

Cellulitis

Interventions

Linezolid

Condition Hierarchy (Ancestors)

Skin Diseases, Infectious; Infections; Suppuration; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Yang NA liecheng, master

  Mabwell (Shanghai) Bioscience Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Shaoqing ZENG, Bachelor

CONTACT

021-58585793; shaoqing.zeng@mabwell.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: April 21, 2022
• Study Start: February 16, 2022
• Primary Completion: October 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 21, 2022

Record last verified: 2022-04

Locations

CN (1)