A Phase 3, Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Contezolid Acefosamil and Contezolid Compared to Linezolid Administered Intravenously and Orally to Adults with Moderate or Severe Diabetic Foot Infections

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Micurx Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

17 Mar 2023 → ongoing

Decision date (initial)

2023-03-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MicuRx Pharmaceuticals, Inc.

External identifiers

EU CT number

2022-500257-16-00

WHO UTN

U1111-1277-0865

ClinicalTrials.gov

NCT05369052

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

• The primary objective is to evaluate the Investigator’s assessment of clinical response at the D35 visit in
subjects receiving contezolid acefosamil/contezolid compared to subjects receiving linezolid in the MITT
analysis set
• Evaluate safety and tolerability of contezolid acefosamil (IV)/contezolid (PO) compared with linezolid (IV
and PO)

Secondary objectives 5

1. Evaluate the Investigator’s assessment of clinical response at: o End-of-Therapy (EOT) visit in the MITT analysis set o D35 visit in the Clinically Evaluable (CE) at D35 (CE-D35) analysis set
2. Evaluate per-subject microbiological response at: o D35 in the Microbiological-MITT (Micro-MITT) analysis set o D35 in Microbiologically Evaluable (ME) at Day 35 (ME-D35) analysis set
3. Evaluate per-pathogen microbiological response at: o D35 in the Micro-MITT and ME-D35 analysis sets o EOT in the Micro-MITT and ME at EOT (ME-EOT) analysis sets
4. Evaluate the composite endpoint of death, unplanned amputation, and infectious complications of the primary DFI by Day 35 in the MITT and CE-D35 analysis sets
5. 5. Evaluate early clinical response as equal or greater than 20% percent reduction in the surface area of redness, edema, and/or induration of the primary DFI site at Day 5 (± 1day), compared to Baseline, in patients who did not receive any rescue antibiotic therapy and are alive in the MITT analysis set.

Conditions and MedDRA coding

Diabetic Foot Infections

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Males or females ≥18 years of age
2. 2. Willing and able to provide written informed consent
3. 3. Have diabetes mellitus (type 1 or 2) per the American Diabetes Association criteria
4. 4. Have a foot infection that started at or below the malleolus and does not extend above the knee. If the subject has multiple infections that meet all the criteria below, the one with the highest IWGDF classification and the largest size will be designated as the primary DFI
5. 5. Foot infection that meets the IWGDF DFI criteria for classification 3 (moderate infection) or 4 (severe infection) (Appendix 8) that are confirmed or suspected to be due to a Gram-positive bacterial pathogen
6. 6. Foot infection had acute onset or worsening of signs and symptoms within the past 14 days
7. 7. Received <48 hours administration of a potentially effective antibiotic (ie, active against all pathogens known to be present) to treat the current target infection within 96 hours before the start of study drug administration
8. 8. Females must be either postmenopausal for ≥2 years or surgically sterile (having undergone tubal ligation, hysterectomy, or bilateral oophorectomy) or, if of childbearing potential, must have a negative pregnancy test at Screening/Baseline and, if sexually active with male partners, be willing to use a highly effective method of contraception throughout the study, such as 1 of the following: a. Hormonal contraception that inhibits the ovulation (stable dose for 3 months) b. Intrauterine device/intrauterine hormone- releasing system
9. 9. Males, if nonsterile and sexually active with female partners of childbearing potential, must abstain from sexual intercourse or have partner(s) who will follow the contraception criteria for female study participants. Male must be willing to continue to use such highly effective birth control measures while participating in the study and for 60 days following participation in the study. Males must also refrain from sperm donations during this time.

Exclusion criteria 28

1. 1. Previous DFI known or suspected to be caused by Gram-positive pathogens that are resistant to oxazolidinone antibiotics
2. 10. Receipt of chemotherapy, radiotherapy, or potent, noncorticosteroid immunosuppressant drugs (eg, cyclosporine, azathioprine, tacrolimus, immune-modulating monoclonal antibody therapy) within the past 3 months, or the receipt of corticosteroids ≥10 mg of prednisone (or equivalent) per day for >14 days in the prior 30 days
3. 11. Known or suspected pheochromocytoma or thyrotoxicosis or severe uncontrolled hypertension.
4. 12. QT interval corrected for heart rate by Fridericia's formula (QTcF) duration >450 msec for males and >470 msec for females obtained as an average from the triplicate Screening/Baseline ECGs, history of QT prolongation, hypokalemia (serum potassium <3.0 mEq/L) at Screening/Baseline, or other proarrhythmic conditions
5. 13. Concomitant condition that, in the opinion of the Investigator, would preclude an evaluation of a response or make it unlikely that the contemplated course of therapy could be completed
6. 14. History of known or suspected serotonin syndrome, neuroleptic malignant syndrome, or carcinoid syndrome
7. 15. History of known or suspected Clostridioides difficile-associated diarrhea
8. 16. History of drug-related peripheral or optic neuropathy (diabetic neuropathy is allowed)
9. 17. History of a seizure disorder or known or suspected central nervous system condition that may predispose to seizures or lower the seizure threshold
10. 18. Females who are pregnant or breastfeeding
11. 19. Prior receipt of any formulation of contezolid acefosamil or contezolid
12. 2. DFI with presumptive evidence or suspicion of osteomyelitis based on three diagnostic methods: X-ray, probe to bone test and erythrocyte sedimentation rate. Either an X-ray from the primary DFI site consistent with osteomyelitis, a positive probe to bone test, or an erythrocyte sedimentation rate (ESR) ≥70 mm/hour, will be evidence enough to suspect osteomyelitis (unless the ESR value only has any other plausible explanation such as rheumatologic disease, cancer, a large DFI infection, and the medical monitor approved such ESR value after his/her assessment). If osteomyelitis is diagnosed or suspected using methods different from those requested during this study (e.g., CT scan or MRI) such patients should not be enrolled either. EXCEPTION: if all infected bone was clearly removed (e.g., toe amputation) within 48 hours before the start of study drug administration but there remains infected soft tissue, the subject is acceptable for enrollment.
13. 20. Prior (within the past 2 weeks) administration of, or expected or required concomitant (from the start of the study drug to EOT) administration of: a. Systemic adrenergic, dopaminergic, or serotonergic medications b. Monoamine oxidase inhibitors (eg, isocarboxazid, isoniazid, nialamide, phenelzine, procarbazine, and hydracarbazine)
14. 22. Expected concurrent hemodialysis, hemofiltration, peritoneal dialysis, or plasmapheresis
15. 23. Inability to tolerate a PO study drug for duration of study treatment (eg, nausea, vomiting, diarrhea, or any other condition that might impair ingestion or absorption of PO study drug)
16. 24. Poor venous access
17. 25. History of any intolerance, hypersensitivity, or allergic reaction to any oxazolidinone antibiotic or excipient in an oxazolidinone antibiotic
18. 26. History of any intolerance, hypersensitivity, or allergic reaction to aztreonam or its excipients; note that while cross-reactivity of aztreonam with other β-lactams is rare, this drug should be administered with caution to any subject with a history of hypersensitivity to β-lactams (eg, penicillins, cephalosporins, carbapenems)
19. 27. History of any intolerance, hypersensitivity, or allergic reaction to metronidazole or metronidazole excipient.
20. 28. Taken any investigational drugs or used any investigational devices within 30 days or 5 half-lives of the study drug, whichever is longer, before randomization
21. 29. Inability to cooperate fully with the requirements of the study protocol, including the schedule of events, or likely to be noncompliant with any study requirements, or the Investigator determines that the subject should not participate in the study
22. 3. DFI without presumptive evidence of osteomyelitis anticipated to require >28 days of antibiotic treatment
23. 4. Necrotizing fasciitis, crepitant cellulitis, wet gangrene, gas gangrene, ecthyma gangrenosum, septic arthritis, or severely impaired arterial supply to any portion of the affected foot which may need revascularization before the end of the study
24. 5. Infected prosthetic materials or devices at the primary DFI site that will not be removed before or at the time of enrollment
25. 6. Anticipated requirement for complete resection or amputation (i.e., removal of all infected tissue with clean margins) of the infected DFI anatomical site within 30 days
26. 7. Known or suspected concurrent infection of any type that would require treatment with a systemic antibacterial agent with activity against Gram-positive bacteria
27. 8. Life expectancy <3 months or evidence of immediately life-threatening disease, including, but not limited to, current or impending respiratory failure, shock, acute coronary syndrome, unstable arrhythmias, hypertensive emergency, acute hepatic failure, active gastrointestinal bleeding, profound metabolic, or acute cerebrovascular events
28. 9. Evidence of significant hepatic, renal, hematologic, or immunologic disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. The primary objective is to evaluate the Investigator’s assessment of clinical response at the D35 visit in subjects receiving contezolid acefosamil/contezolid compared to subjects receiving linezolid in the MITT analysis set
2. 2. Evaluate safety and tolerability of contezolid acefosamil (IV)/contezolid (PO) compared with linezolid (IV and PO)

Secondary endpoints 7

1. 1. Evaluate the Investigator’s assessment of clinical response at End-of-Therapy (EOT) visit in the MITT analysis set
2. 2. Evaluate the Investigator’s assessment of clinical response at D35 visit in the Clinically Evaluable (CE) at D35 (CE-D35) analysis set
3. 3. Per-subject microbiological response at D35
4. 4. Per-pathogen microbiological response at D35
5. 5. Per-pathogen microbiological response at EOT
6. 6. Composite endpoint of death, unplanned amputation, and infectious complications of the primary DFI by Day 35
7. 7. Evaluate early clinical response as equal or greater than 20% percent reduction in the surface area of redness, edema, and/or induration of the primary DFI site at Day 5 (± 1day), compared to Baseline, in patients who did not receive any rescue antibiotic therapy and are alive in the MITT analysis set.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Micurx Pharmaceuticals Inc.

Sponsor organisation

Micurx Pharmaceuticals Inc.

Address

950 Tower Lane Ste 390

City

Foster City

Postcode

94404-2123

Country

United States

Scientific contact point

Organisation

Micurx Pharmaceuticals Inc.

Contact name

Regis Vilchez

Public contact point

Organisation

Micurx Pharmaceuticals Inc.

Contact name

Regis Vilchez

Third parties 7

Locations

15 EU/EEA countries · 58 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 344 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

30 submissions — initial application plus substantial / non-substantial modifications