Community-acquired Bacterial Pneumonia
Conditions
Keywords
pneumonia, macrolide, pediatric
Brief summary
This is a phase 2/3, randomized, open-label, active control, multi-center study to assess the safety and efficacy of solithromycin in children and adolescents with community-acquired bacterial pneumonia (CABP).
Detailed description
Subjects who meet all inclusion/exclusion criteria and sign the informed consent/assent were enrolled. Subjects were randomized to receive solithromycin or a comparator antibiotic, administered IV and/or by mouth (PO) based on weight and age. Subjects were treated daily for 5 to 7 days with oral solithromycin and 5 to 7 days with IV or IV-to-oral solithromycin. Subjects were treated for 5 to 10 days with comparator antibiotics. Subjects received safety and efficacy assessments during and after treatment.
Interventions
DRUGSolithromycin
DRUGStandard of Care
Age- and weight-based dosing as appropriate per sites standard of care.
Sponsors
Biomedical Advanced Research and Development Authority
Melinta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
A healthcare provider designated as a sub-investigator blinded to treatment allocation at the site documented clinical response at specified time points during the study.
Eligibility
Sex/Gender
ALL
Age
2 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
* History of and/or documented fever (rectal, ear, or oral temperature ≥38°C or axillary temperature ≥37.5°C) or hypothermia (rectal, ear, or oral temperature \<35°C or axillary temperature \<34.5°C) * Chest radiograph infiltrates consistent with bacterial pneumonia (or pneumonia caused by atypical bacterial agents); if a subject is outpatient and starting on oral therapy, a radiograph is not required. * Presence of at least 2 of the following signs or symptoms: * Cough * Difficulty breathing * Production of purulent sputum * Chest pain * Grunting * Hypotension * Tachycardia, defined as follows: 2 months to \<24 months: ≥160 beats/min 24 months to \<10 years: ≥140 beats/min * 10 years: ≥100 beats/min * Tachypnea, defined as follows: 2 months to \<12 months: ≥50 breaths/min 12 months to \<5 years: ≥40 breaths/min * 5 years: ≥20 breaths/min * Physical exam consistent with pulmonary consolidation * Presence of at least 1 of the following: * Leukocytosis (≥12,000 white blood cells \[WBC\]/mm3) * Leukopenia (\<5000 WBC/mm3) * ≥10% immature neutrophils (bands) regardless of total peripheral WBC * Elevated inflammatory markers (C-reactive protein or procalcitonin) * Oxygen saturation \<97% on room air * Organism consistent with a typical respiratory pathogen identified
Exclusion criteria
* Ventilator-associated or hospital-acquired pneumonia * \>48 hours of systemic antibacterial therapy * confirmed or suspected bacterial meningitis * breast-feeding females * positive pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overview of Adverse Events By Treatment Arm | Up to 28 days post-treatment | Summary of subjects experiencing Treatment Emergent Adverse Events (TEAE) through Day 16 visit and Treatment Emergent Serious Adverse Events (TESAE) through Day 28 visit (28 days +/- 4 days after randomization) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Early Clinical Response | During Treatment Days 3 to 4 | Early clinical response (ECR) was defined using the latest efficacy evaluation from Day 2 (if subject discharged prior to Day 2), Day3, or Day 4, and was defined as improvement in at least 1 presenting sign/symptom of CABP with no deterioration in any signs/symptoms of CABP and no requirement for an additional antibiotic. |
| Summary of Clinical Improvement | Last day of Treatment (+48 hours) | Clinical improvement was assessed using the latest efficacy evaluation conducted on last day of treatment (+48 hours), and was defined identically to the early clinical response. |
| Summary of Clinical Cure | Short-term follow-up at 16 days (+/- 4 days) | Clinical cure was assessed using the latest efficacy evaluation conducted on Day 16 (+/- 4 days) post-randomization, and was defined as resolution of all presenting signs/symptoms of CABP (excluding cough), no development of new signs/symptoms of CABP, and no requirement for an additional antibiotic. |
Countries
Bulgaria, Hungary, Philippines, Spain, United Kingdom, United States
Participant flow
Recruitment details
Subjects who met all inclusion/exclusion criteria and sign the informed consent/assent were enrolled. Subjects were randomized to receive solithromycin or a comparator antibiotic, administered IV and/or by mouth (PO) based on weight and age. Subjects received safety and efficacy assessments during and after treatment.
Participants by arm
| Arm | Count |
|---|---|
| Solithromycin Solithromycin was dosed for 5-7 days. | 70 |
| Standard of Care Comparators were does up to 10 days per site standard of care. | 24 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Solithromycin | Standard of Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 70 Participants | 24 Participants | 94 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 9.48 years STANDARD_DEVIATION 4.71 | 9.65 years STANDARD_DEVIATION 4.95 | 9.57 years STANDARD_DEVIATION 4.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 21 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 4 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 2 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 47 Participants | 16 Participants | 63 Participants |
| Region of Enrollment Bulgaria | 21 participants | 6 participants | 27 participants |
| Region of Enrollment Hungary | 19 participants | 4 participants | 23 participants |
| Region of Enrollment Philippines | 12 participants | 4 participants | 16 participants |
| Region of Enrollment Spain | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 18 participants | 9 participants | 27 participants |
| Sex: Female, Male Female | 30 Participants | 11 Participants | 41 Participants |
| Sex: Female, Male Male | 40 Participants | 13 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 24 |
| other Total, other adverse events | 24 / 70 | 7 / 24 |
| serious Total, serious adverse events | 1 / 70 | 1 / 24 |
Outcome results
Primary
Overview of Adverse Events By Treatment Arm
Summary of subjects experiencing Treatment Emergent Adverse Events (TEAE) through Day 16 visit and Treatment Emergent Serious Adverse Events (TESAE) through Day 28 visit (28 days +/- 4 days after randomization)
Time frame: Up to 28 days post-treatment
Population: Treatment through Day 28 (28 days +/- 4days after randomization)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Solithromycin | Overview of Adverse Events By Treatment Arm | TEAE | 24 Participants |
| Solithromycin | Overview of Adverse Events By Treatment Arm | TESAE | 1 Participants |
| Standard of Care | Overview of Adverse Events By Treatment Arm | TEAE | 7 Participants |
| Standard of Care | Overview of Adverse Events By Treatment Arm | TESAE | 1 Participants |
95% CI: [23, 47]Clopper-Pearson
Secondary
Summary of Clinical Cure
Clinical cure was assessed using the latest efficacy evaluation conducted on Day 16 (+/- 4 days) post-randomization, and was defined as resolution of all presenting signs/symptoms of CABP (excluding cough), no development of new signs/symptoms of CABP, and no requirement for an additional antibiotic.
Time frame: Short-term follow-up at 16 days (+/- 4 days)
Population: Not all subjects had the Clinical cure assessment performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Solithromycin | Summary of Clinical Cure | 60.0 percentage of participants |
| Standard of Care | Summary of Clinical Cure | 68.4 percentage of participants |
95% CI: [50, 73]Clopper-Pearson
Secondary
Summary of Clinical Improvement
Clinical improvement was assessed using the latest efficacy evaluation conducted on last day of treatment (+48 hours), and was defined identically to the early clinical response.
Time frame: Last day of Treatment (+48 hours)
Population: Not all subjects had the Clinical Improvement assessment performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Solithromycin | Summary of Clinical Improvement | 64.5 percentage of participants |
| Standard of Care | Summary of Clinical Improvement | 81 percentage of participants |
95% CI: [58, 78]Clopper-Pearson
Secondary
Summary of Early Clinical Response
Early clinical response (ECR) was defined using the latest efficacy evaluation from Day 2 (if subject discharged prior to Day 2), Day3, or Day 4, and was defined as improvement in at least 1 presenting sign/symptom of CABP with no deterioration in any signs/symptoms of CABP and no requirement for an additional antibiotic.
Time frame: During Treatment Days 3 to 4
Population: Not all subjects had the Early Clinical Improvement assessment performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Solithromycin | Summary of Early Clinical Response | 66.7 percentage of participants |
| Standard of Care | Summary of Early Clinical Response | 46.7 percentage of participants |
95% CI: [49, 74]Clopper-Pearson