Date: 2017-02-24
Type of
information: Results
phase: 3
Announcement: results
Company: Cempra (USA - NC)
Product: Taksta™ (CEM-102, sodium fusidate, sodium salt of fusidic acid)
Action
mechanism:
- antibiotic. Fusidic acid is orally active against gram-positive bacteria, including Staphylococcus aureus strains such as healthcare-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) and community-acquired MRSA. Cempra is developing fusidic acid exclusively in the U.S. for ABSSSI and is exploring its use for the long term oral treatment of refractory bone and joint infections.
Disease: acute bacterial skin and skin structure infections (ABSSSI)
Therapeutic
area: Infectious diseases
Country: USA
Trial
details: The study is a phase 3, randomized, double-blind, multi-center efficacy and safetytrial to evaluate an oral CEM-102 loading dose regimen compared to oral linezolid in the treatment of subjects with ABSSSI. The study was conducted at 62 sites in the United States . Patients randomized to treatment with oral fusidic acid received a loading dose of 1500 mg every 12 hours for two doses, followed by 600 mg every 12 hours thereafter, until the end of a 10 day course of therapy. Patients randomized to treatment with the active comparator, oral linezolid, received 600 mg every 12 hours for 10 days. Randomization was 1:1 and was stratified by type of infection (cellulitis, wound infection, major cutaneous abscess), by age and by prior use of an antibiotic within 36 hours prior to randomization. (NCT02570490)
Latest
news:
- • On February 24, 2017, Cempra announced results from a phase 3 study of oral fusidic acid in 716 patients with acute bacterial skin and skin structure infections (ABSSSI). Fusidic acid was well tolerated in the study and achieved the primary endpoint, demonstrating non-inferiority (NI) (10% NI margin) of oral fusidic acid compared to oral linezolid for early clinical response in the intent to treat patient population.
- Balanced Baseline Demographic Characteristics
| ITT Population |
Fusidic Acid
N=359 |
Linezolid
N=357 |
| Sex, n (%) |
|
|
| Male |
244 (68.0) |
218 (61.1) |
| Female |
115 (32.0) |
139 (38.9) |
| Infection Type, n (%) |
|
|
| Major Cutaneous Abscess |
46 (12.8) |
47 (13.2) |
| Cellulitis |
92 (25.6) |
92 (25.8) |
| Wound Infection |
221 (61.6) |
218 (61.1) |
| Prior Antibiotic Usage, n (%) |
|
|
| Yes |
17 (4.7) |
18 (5.0) |
| No |
342 (95.3) |
339 (95.0) |
| Recent or Ongoing IV Drug Abuse, n (%) |
|
|
| Yes |
245 (68.2) |
238 (66.7) |
| No |
114 (31.8) |
119 (33.3) |
- Consistent Efficacy at ECR, End-of-Treatment (EOT) and Post-therapy Evaluation (PTE): The primary endpoint, early clinical response in the intent to treat population, was defined as the proportion of patients alive and achieving a ? 20 percent reduction from baseline in lesion size at 48-72 hours after the start of study drug, without receiving rescue antibiotics. In the study, 87.2 percent of intent to treat patients receiving fusidic acid demonstrated ECR, compared to 86.6 percent of intent to treat patients receiving linezolid (treatment difference 0.6%, 95% confidence interval (CI) -4.6, +5.9), demonstrating non-inferiority to linezolid.
- Fusidic acid also showed comparable efficacy to linezolid in investigator-assessed clinical response in the intent to treat and clinically evaluable (CE) populations at EOT and PTE (7-14 days post-EOT) visits.
- Clinical Response by Population
|
Fusidic Acid |
Linezolid |
Treatment Difference (95% CI) |
| ITT Population |
|
|
|
| ECR (Primary Endpoint) |
87.2 % (313/359) |
86.6 % (309/357) |
+0.6 (-4.6, +5.9) |
| Clinical Success at EOT |
91.9 % (330/359) |
89.6 % (320/357) |
+2.3 (-2.2, +6.8) |
| Clinical Success at PTE |
88.6 % (320/359) |
88.5 % (316/357) |
+0.1 (-4.9, +5.0) |
| CE Populations |
|
|
|
| Clinical Success at EOT (CE-EOT) |
97.1 % (303/312) |
97.3 % (288/296) |
-0.2 (-3.1, +2.8) |
| Clinical Success at PTE (CE-PTE) |
95.7 % (292/305) |
96.9 % (283/292) |
-1.2 (-4.5, +2.2) |
- Strong Activity Against Key Pathogens, Including MRSA: Microbiological response rates by pathogen were high in both treatment groups in both the microbiological ITT (mITT) and microbiologically-evaluable (ME) patient populations (patients with isolation of a baseline pathogen, who were also clinically evaluable). The most common pathogens identified were Staphylococcus aureus, Streptococcus anginosus group species, Streptococcus pyogenes and Clostridium species.
- Notably, the microbiological success rate among fusidic acid recipients in each ME population with methicillin-resistant S. aureus (MRSA) infection was 100 percent (99/99) at both the EOT and PTE visits.
- Fusidic Acid Well Tolerated: Fusidic acid was well tolerated in the study. The rates of treatment-emergent adverse events (TEAEs) were comparable between treatment groups (37.9 percent fusidic acid, 36.1 percent linezolid). The most common TEAEs in both treatment groups were gastrointestinal events (22.8 percent fusidic acid, 18.2 percent linezolid). Serious adverse events (SAEs) occurred in six fusidic acid recipients and eight linezolid recipients, and were considered study-drug related in one fusidic acid recipient (vomiting) and in two linezolid recipients (one drug induced liver injury, one vomiting). Adverse events led to study drug discontinuation in 2.2 percent of fusidic acid recipients, and 2.0 percent of linezolid recipients. There was one death in the study, an event due to illicit drug overdose and aspiration which occurred in a patient receiving linezolid. Rates of treatment-emergent ALT elevation to > 3x ULN occurred in 1.0 percent of fusidic acid recipients and 0.7 percent of linezolid patients.
- • On December 8, 2015, Cempra announced that the first patient has been dosed in its Phase 3 clinical trial to evaluate the safety and efficacy of oral Taksta™ (CEM-102, sodium fusidate, the sodium salt of fusidic acid) as a potential treatment for acute bacterial skin and skin structure infections (ABSSSI). Cempra is developing Taksta® exclusively in the United States as an oral treatment for ABSSSI and refractory bone and joint infections. The Phase 3 clinical trial is designed to evaluate the efficacy and safety of Taksta® in the treatment of ABSSSI. Approximately 712 patients, 12 years old and up and diagnosed with ABSSSI, will be randomized one to one to receive either Taksta® or Zyvox® (linezolid). The primary objective is to demonstrate non-inferiority of Taksta® compared to Zyvox® for early clinical response (ECR) defined as the proportion of patients alive and achieving a ? 20% reduction from baseline in lesion size at 48-72 hours after start of study drug. Patients randomized to treatment with Taksta® will receive 1500 mg by mouth every 12 hours for 2 doses, followed by 600 mg by mouth every 12 hours thereafter, until the end of therapy (10 days total). Patients randomized to the active comparator, linezolid, will be dosed with oral 600 mg every 12 hours for 10 days. Secondary outcome measures will assess the proportion of subjects with clinical success at their post-treatment evaluation 7 to 14 days after the end of treatment in the intent to treat and clinically evaluable patient groups. The incidence of adverse events will be recorded and clinical laboratory evaluations will be conducted. The design of this study conforms to FDA guidelines for conducting clinical trials in ABSSSI published in October 2013 .
Is
general: Yes
