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

Primary Purpose

Renal Impairment

Status
Completed
Phase
Phase 1
Locations
New Zealand
Study Type
Interventional
Intervention
SPR206
Sponsored by
Spero Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Renal Impairment focused on measuring End State Renal Disease (ESRD), Renal Insufficiency, Renal Impairment, Renal Disease, Hemodialysis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Medical Facility
  • Medical Facility

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SPR206

Arm Description

SPR206 100mg single-dose IV infused over 1 hour

Outcomes

Primary Outcome Measures

Time to the maximum plasma concentration (Tmax)
Maximum plasma concentration (Cmax)
Area under the concentration-time curve from time 0 to last measurable timepoint (AUC0-t)
Area under the concentration-time curve from time 0 to infinity (AUC0-∞)

Secondary Outcome Measures

Area under the concentration-time curve from time 0 to 8 hours (AUC0-8)
Terminal Elimination Rate Constant (kel)
Terminal half-life (t1/2)
Total body clearance (CL)
Renal clearance (CLR)
Steady-state volume of distribution (Vss)
Amount of drug excreted in urine by interval (Aet) for Cohorts 1-4
Cumulative amount of drug excreted in urine at the end of each interval (Aeu) for Cohorts 1-4
Fraction of drug excreted in the urine expressed as a percentage (Ae%) for Cohorts 1-4
Fraction of dose excreted in the urine over a collection interval (Fe) for Cohorts 1-4
Cumulative fraction of dose excreted in the urine over (Feu) for Cohorts 1-4
Extraction ratio (ER) for subjects on dialysis (Cohort 5)
Estimated hemodialysis clearance (CLHD) for subjects on dialysis (Cohort 5)
Amount of the dose removed by hemodialysis (XHD) for subjects on dialysis (Cohort 5)
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 26, 2021
Last Updated
December 14, 2021
Sponsor
Spero Therapeutics
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT04865393
Brief Title
Phase 1 Study of PK and Safety of SPR206 in Subjects With Various Degrees Of Renal Function
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
June 8, 2021 (Actual)
Primary Completion Date
December 1, 2021 (Actual)
Study Completion Date
December 6, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spero Therapeutics
Collaborators
United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment
Keywords
End State Renal Disease (ESRD), Renal Insufficiency, Renal Impairment, Renal Disease, Hemodialysis

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SPR206
Arm Type
Experimental
Arm Description
SPR206 100mg single-dose IV infused over 1 hour
Intervention Type
Drug
Intervention Name(s)
SPR206
Intervention Description
SPR206 100 mg single-dose IV infused over 1 hour
Primary Outcome Measure Information:
Title
Time to the maximum plasma concentration (Tmax)
Time Frame
36 hours after start of study drug IV infusion
Title
Maximum plasma concentration (Cmax)
Time Frame
36 hours after start of study drug IV infusion
Title
Area under the concentration-time curve from time 0 to last measurable timepoint (AUC0-t)
Time Frame
36 hours after start of study drug IV infusion
Title
Area under the concentration-time curve from time 0 to infinity (AUC0-∞)
Time Frame
36 hours after start of study drug IV infusion
Secondary Outcome Measure Information:
Title
Area under the concentration-time curve from time 0 to 8 hours (AUC0-8)
Time Frame
8 hours after start of study drug IV infusion
Title
Terminal Elimination Rate Constant (kel)
Time Frame
36 hours after start of study drug IV infusion
Title
Terminal half-life (t1/2)
Time Frame
36 hours after start of study drug IV infusion
Title
Total body clearance (CL)
Time Frame
36 hours after start of study drug IV infusion
Title
Renal clearance (CLR)
Time Frame
36 hours after start of study drug IV infusion
Title
Steady-state volume of distribution (Vss)
Time Frame
36 hours after start of study drug IV infusion
Title
Amount of drug excreted in urine by interval (Aet) for Cohorts 1-4
Time Frame
36 hours after start of study drug IV infusion
Title
Cumulative amount of drug excreted in urine at the end of each interval (Aeu) for Cohorts 1-4
Time Frame
36 hours after start of study drug IV infusion
Title
Fraction of drug excreted in the urine expressed as a percentage (Ae%) for Cohorts 1-4
Time Frame
36 hours after start of study drug IV infusion
Title
Fraction of dose excreted in the urine over a collection interval (Fe) for Cohorts 1-4
Time Frame
36 hours after start of study drug IV infusion
Title
Cumulative fraction of dose excreted in the urine over (Feu) for Cohorts 1-4
Time Frame
36 hours after start of study drug IV infusion
Title
Extraction ratio (ER) for subjects on dialysis (Cohort 5)
Time Frame
Up to 1 day post dose - between start and end of hemodialysis
Title
Estimated hemodialysis clearance (CLHD) for subjects on dialysis (Cohort 5)
Time Frame
Up to 1 day post dose - between start and end of hemodialysis
Title
Amount of the dose removed by hemodialysis (XHD) for subjects on dialysis (Cohort 5)
Time Frame
Up to 1 day post dose - between start and end of hemodialysis
Title
Incidence of Treatment-Emergent Adverse Events
Description
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.
Time Frame
14 days post start of last study drug IV infusion
Title
Incidence of abnormal vital sign assessments - blood pressure
Description
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.
Time Frame
14 days post study drug IV infusion
Title
Incidence of abnormal vital sign assessments - body temperature
Description
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.
Time Frame
14 days post study drug IV infusion
Title
Incidence of abnormal physical exam assessments
Description
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.
Time Frame
14 days post study drug IV infusion
Title
Incidence of abnormal ECG assessments - heart rate
Description
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.
Time Frame
14 days post study drug IV infusion
Title
Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval
Description
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.
Time Frame
14 days post study drug IV infusion
Title
Incidence of abnormal safety laboratory assessments
Description
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.
Time Frame
14 days post study drug IV infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Melnick, MD
Organizational Affiliation
Spero Therapeutics Inc
Official's Role
Study Director
Facility Information:
Facility Name
Medical Facility
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
Medical Facility
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
No

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

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