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

• ClinicalTrials.gov Identifier: NCT04865393
• Recruitment Status: Completed
• First Posted: April 29, 2021
• Last Update Posted: December 15, 2021
• Sponsor: Spero Therapeutics
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): Spero Therapeutics

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 (Clinical Trial)
• 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: June 8, 2021
• Actual Primary Completion Date: December 1, 2021
• Actual Study Completion Date: December 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

Outcome Measures

Primary Outcome Measures :

1. Time to the maximum plasma concentration (Tmax) [ Time Frame: 36 hours after start of study drug IV infusion ]
2. Maximum plasma concentration (Cmax) [ Time Frame: 36 hours after start of study drug IV infusion ]
3. 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 ]
4. 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 Measures :

1. 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 ]
2. Terminal Elimination Rate Constant (kel) [ Time Frame: 36 hours after start of study drug IV infusion ]
3. Terminal half-life (t1/2) [ Time Frame: 36 hours after start of study drug IV infusion ]
4. Total body clearance (CL) [ Time Frame: 36 hours after start of study drug IV infusion ]
5. Renal clearance (CLR) [ Time Frame: 36 hours after start of study drug IV infusion ]
6. Steady-state volume of distribution (Vss) [ Time Frame: 36 hours after start of study drug IV infusion ]
7. Amount of drug excreted in urine by interval (Aet) for Cohorts 1-4 [ Time Frame: 36 hours after start of study drug IV infusion ]
8. 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 ]
9. 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 ]
10. 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 ]
11. 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 ]
12. Extraction ratio (ER) for subjects on dialysis (Cohort 5) [ Time Frame: Up to 1 day post dose - between start and end of hemodialysis ]
13. Estimated hemodialysis clearance (CLHD) for subjects on dialysis (Cohort 5) [ Time Frame: Up to 1 day post dose - between start and end of hemodialysis ]
14. 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 ]
15. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 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.
16. Incidence of abnormal vital sign assessments - blood pressure [ Time Frame: 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.
17. Incidence of abnormal vital sign assessments - body temperature [ Time Frame: 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.
18. Incidence of abnormal physical exam assessments [ Time Frame: 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.
19. Incidence of abnormal ECG assessments - heart rate [ Time Frame: 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.
20. Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval [ Time Frame: 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.
21. Incidence of abnormal safety laboratory assessments [ Time Frame: 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

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

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

Contacts and Locations

Locations

New Zealand

Medical Facility

Auckland, New Zealand, 1010

Medical Facility

Christchurch, New Zealand, 8011

Sponsors and Collaborators

Spero Therapeutics

United States Department of Defense

Investigators

• Study Director: David Melnick, MD; Spero Therapeutics Inc

More Information

• Responsible Party: Spero Therapeutics
• ClinicalTrials.gov Identifier: NCT04865393
• Other Study ID Numbers: SPR206-103; CDMRP-JW180095-B ( Other Grant/Funding Number: United States Department of Defense )
• First Posted: April 29, 2021
• Last Update Posted: December 15, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Spero Therapeutics:

End State Renal Disease (ESRD); Renal Insufficiency; Renal Impairment; Renal Disease; Hemodialysis

Additional relevant MeSH terms:

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases