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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: SPR206

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 1010
    • Medical facility
  • Christchurch, New Zealand, 8011
    • Medical facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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	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.	14 days post start of last study drug IV infusion
Incidence of abnormal vital sign assessments - blood pressure	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.	14 days post study drug IV infusion
Incidence of abnormal vital sign assessments - body temperature	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.	14 days post study drug IV infusion
Incidence of abnormal physical exam assessments	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.	14 days post study drug IV infusion
Incidence of abnormal ECG assessments - heart rate	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.	14 days post study drug IV infusion
Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval	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.	14 days post study drug IV infusion
Incidence of abnormal safety laboratory assessments	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.	14 days post study drug IV infusion

Collaborators and Investigators

• Sponsor: Spero Therapeutics
• Collaborators: United States Department of Defense
• Investigators: Study Director: David Melnick, MD, Spero Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2021
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 6, 2021

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Renal Impairment; Renal Insufficiency; Hemodialysis; End State Renal Disease (ESRD); Renal Disease
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency
• Other Study ID Numbers: SPR206-103; CDMRP-JW180095-B (Other Grant/Funding Number: United States Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No