Phase 1 Study of PK and Safety of SPR206 in Subjects With Various Degrees Of Renal Function

Sponsor

Spero Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT04865393

Collaborator

United States Department of Defense (U.S. Fed)

Enrollment

Locations

Arm

5.9

Actual Duration (Months)

18.5

Patients Per Site

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Evaluation of the pharmacokinetics (PK) of SPR206 in subjects with normal renal function, subjects with various degrees of renal insufficiency, and subjects with end-stage renal disease (ESRD) receiving hemodialysis (HD) therapy.

Condition or Disease	Intervention/Treatment	Phase
Renal Impairment	Drug: SPR206	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Phase 1, Open-label Study to Assess the Safety and Pharmacokinetics of SPR206 Following a Single IV Dose of SPR206 in Subjects With Varying Degrees of Renal Function

Actual Study Start Date :

Jun 8, 2021

Actual Primary Completion Date :

Dec 1, 2021

Actual Study Completion Date :

Dec 6, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SPR206 SPR206 100mg single-dose IV infused over 1 hour	Drug: SPR206 SPR206 100 mg single-dose IV infused over 1 hour

Arm

Intervention/Treatment

Experimental: SPR206

SPR206 100mg single-dose IV infused over 1 hour

Drug: SPR206

SPR206 100 mg single-dose IV infused over 1 hour

Outcome Measures

Primary Outcome Measures

Time to the maximum plasma concentration (Tmax) [36 hours after start of study drug IV infusion]
Maximum plasma concentration (Cmax) [36 hours after start of study drug IV infusion]
Area under the concentration-time curve from time 0 to last measurable timepoint (AUC0-t) [36 hours after start of study drug IV infusion]
Area under the concentration-time curve from time 0 to infinity (AUC0-∞) [36 hours after start of study drug IV infusion]

Secondary Outcome Measures

Area under the concentration-time curve from time 0 to 8 hours (AUC0-8) [8 hours after start of study drug IV infusion]
Terminal Elimination Rate Constant (kel) [36 hours after start of study drug IV infusion]
Terminal half-life (t1/2) [36 hours after start of study drug IV infusion]
Total body clearance (CL) [36 hours after start of study drug IV infusion]
Renal clearance (CLR) [36 hours after start of study drug IV infusion]
Steady-state volume of distribution (Vss) [36 hours after start of study drug IV infusion]
Amount of drug excreted in urine by interval (Aet) for Cohorts 1-4 [36 hours after start of study drug IV infusion]
Cumulative amount of drug excreted in urine at the end of each interval (Aeu) for Cohorts 1-4 [36 hours after start of study drug IV infusion]
Fraction of drug excreted in the urine expressed as a percentage (Ae%) for Cohorts 1-4 [36 hours after start of study drug IV infusion]
Fraction of dose excreted in the urine over a collection interval (Fe) for Cohorts 1-4 [36 hours after start of study drug IV infusion]
Cumulative fraction of dose excreted in the urine over (Feu) for Cohorts 1-4 [36 hours after start of study drug IV infusion]
Extraction ratio (ER) for subjects on dialysis (Cohort 5) [Up to 1 day post dose - between start and end of hemodialysis]
Estimated hemodialysis clearance (CLHD) for subjects on dialysis (Cohort 5) [Up to 1 day post dose - between start and end of hemodialysis]
Amount of the dose removed by hemodialysis (XHD) for subjects on dialysis (Cohort 5) [Up to 1 day post dose - between start and end of hemodialysis]
Incidence of Treatment-Emergent Adverse Events [14 days post start of last study drug IV infusion]
To assess the incidents of treatment-emergent adverse events following SPR206 intravenous dose administration. AEs will be classified by System Organ Class (SOC) and Preferred Term (PT). Incidence, frequency, severity and duration will be presented.
Incidence of abnormal vital sign assessments - blood pressure [14 days post study drug IV infusion]
To assess the incidents of abnormal systolic and diastolic blood pressure assessments following SPR206 intravenous dose administration. Values and changes from baseline at each scheduled time-point will be summarized using descriptive statistics (n, mean, SD, median, minimum, and maximum). Significant changes from baseline will be presented.
Incidence of abnormal vital sign assessments - body temperature [14 days post study drug IV infusion]
To assess the incidents of abnormal body temperature assessments following SPR206 intravenous dose administration. Values and changes from baseline at each scheduled time-point will be summarized using descriptive statistics (n, mean, SD, median, minimum, and maximum). Significant changes from baseline will be presented.
Incidence of abnormal physical exam assessments [14 days post study drug IV infusion]
To assess the incidents of abnormal body system assessments following SPR206 intravenous dose administration. Changes from baseline in physical examination findings will be classified as Normal, Abnormal NCS, and Abnormal CS. Frequency counts will be presented.
Incidence of abnormal ECG assessments - heart rate [14 days post study drug IV infusion]
To assess the incidents of abnormal heart rate assessment following SPR206 intravenous dose administration. Cardiac (12-Lead ECG) for heart rate will be classified as normal, abnormality that is NCS, and CS abnormality. Frequency counts by dose group and timepoint of collection will be presented.
Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval [14 days post study drug IV infusion]
To assess the incidents of abnormal PR interval, RR interval, QRS interval, QT interval and QTcF interval assessments following SPR206 intravenous dose administration. Cardiac (12-Lead ECG) results will be classified as normal, abnormality that is NCS, and CS abnormality. Frequency counts by dose group and timepoint of collection will be presented.
Incidence of abnormal safety laboratory assessments [14 days post study drug IV infusion]
To assess the incidents of abnormal hematology, serum chemistry, coagulation and urinalysis assessments following SPR206 intravenous dose administration. Values and changes from baseline at each scheduled time-point will be summarized using descriptive statistics (n, mean, SD, median, minimum, and maximum). Frequency counts of significant changes from baseline will be presented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Key Inclusion Criteria:

BMI ≥ 18.5 and ≤ 39.9 (kg/m2) and weight between 50.0 and 130.0 kg (inclusive)
Medically healthy without clinically significant abnormalities (Healthy Volunteers) or medically stable without clinically significant acute or chronic illness (Subjects with varying degrees of Renal Disease)
Normal renal function with eGFR ≥90 mL/min/1.73m2 (Cohort 1), or renal insufficiency with eGFR 60 to <90 mL/min/1.73m2 (Cohort 2), 30 to <60 mL/min/1.73m2 (Cohort 3), or <30 mL/min/1.73m2 (Cohort 4), calculated using Modification of Diet in Renal Disease (MDRD). Subjects with ESRD must be receiving hemodialysis at least 3 times per week for at least 3 months at Screening (Cohort 5 only)
Non-smoker for at least 1 month prior to screening for the study
Ability and willingness to abstain from alcohol, caffeine, xanthine-containing beverages or food
Other inclusion criteria per protocol

Key Exclusion Criteria:

Any clinically significant medical history or abnormal findings upon physical examination, or clinical laboratory tests, not specifically excluded in other criteria below that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject
Electrocardiogram (ECG) with QTcF interval duration equal or greater than 500 msec
Hemoglobin (HB), hematocrit (HCT), white blood cell count (WBC), or platelet count less than the lower limit of normal range of the reference laboratory (Cohort 1). HB <8.5 gm/dL, WBC ≤3,000 cells/μL or platelet count ≤100,000 cells/μL (Cohorts 2-5)
Results of biochemistry tests for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin greater than 1.5 X the upper limit of normal (ULN) for the reference laboratory
Recent history (within 6 months) of known or suspected Clostridium difficile infection
History of chronic liver disease, cirrhosis, or biliary disease
History of seizure disorder except childhood history of febrile seizures
Positive urine drug/alcohol testing
Positive testing for human immunodeficiency virus1/2 (HIV 1/2), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibodies
History of substance abuse or alcohol abuse
Known history of clinically significant hypersensitivity reaction or anaphylaxis to any medication
Other exclusion criteria per protocol