Study to Assess the Intrapulmonary Pharmacokinetics of SPR206 in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT04868292
• Recruitment Status: Completed
• First Posted: April 30, 2021
• Last Update Posted: November 17, 2021
• Sponsor: Spero Therapeutics
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): Spero Therapeutics

Study Description

Brief Summary:

To evaluate the intrapulmonary pharmacokinetics (PK), including epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations, of SPR206 as well as plasma concentrations of SPR206 in healthy adult volunteers.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: SPR206	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1, Single-Center, Open-Label Study to Assess the Intrapulmonary Pharmacokinetics of SPR206 by Comparing the Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations Following the Intravenous Administration of SPR206 in Healthy Volunteers
• Actual Study Start Date: June 3, 2021
• Actual Primary Completion Date: September 16, 2021
• Actual Study Completion Date: September 29, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: SPR206; Healthy subjects meeting eligibility criteria will receive a total of three 100 mg SPR206 intravenous doses administered every 8 hours.	Drug: SPR206; Three 100 mg SPR206 intravenous doses administered every 8 hours

Outcome Measures

Primary Outcome Measures :

1. Area under the concentration-time curve from time 0 to 8 hours (AUC0-8) for ELF, AM, and plasma [ Time Frame: 8 hours after the start of the third study drug IV infusion ]
2. Maximum observed concentration (Cmax) for ELF, AM, and plasma [ Time Frame: 8 hours after the start of the third study drug IV infusion ]
3. Minimum concentration (Cmin) for ELF, AM, and plasma [ Time Frame: 8 hours after the start of the third study drug IV infusion ]
4. Time to the maximum observed concentration (Tmax) for ELF, AM, and plasma [ Time Frame: 8 hours after the start of the third study drug IV infusion ]

Secondary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of treatment-emergent adverse events following three 100mg SPR206 intravenous doses administered every 8 hours. AEs will be classified by System Organ Class (SOC) and Preferred Term (PT). Incidence, frequency, severity and duration will be presented.
2. Incidence of abnormal vital sign assessments - blood pressure [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of abnormal systolic and diastolic blood pressure assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency count of significant changes from baseline will be presented.
3. Incidence of abnormal vital sign assessments - body temperature [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of abnormal body temperature assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency count of significant changes from baseline will be presented.
4. Incidence of abnormal vital sign assessments - heart rate [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of abnormal heart rate assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency count of significant changes from baseline will be presented.
5. Incidence of abnormal vital sign assessments - respiratory rate [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of abnormal respiratory rate assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency count of significant changes from baseline will be presented.
6. Incidence of abnormal physical exam assessments [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of abnormal body system assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Changes from baseline in physical examination findings will be classified as Normal, Abnormal NCS, and Abnormal CS. Frequency counts will be presented.
7. Incidence of abnormal ECG assessments - heart rate [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of abnormal heart rate assessment following three 100mg SPR206 intravenous doses administered every 8 hours. 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.
8. Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of abnormal PR interval, RR interval, QRS interval, QT interval and QTcF interval assessments following three 100mg SPR206 intravenous doses administered every 8 hours. 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.
9. Incidence of abnormal safety laboratory assessments [ Time Frame: Day -1 to Day 7 ]
   To assess the incidents of abnormal hematology, serum chemistry, coagulation and urinalysis assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency counts of significant changes from baseline will be presented.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Non-smoker for at least 12 months prior to screening for the study
• BMI ≥ 18.5 and ≤ 32 (kg/m2) and weight between 55.0 and 100.0 kg (both inclusive)
• Medically healthy without clinically significant abnormalities as assessed by the Investigator based on screening medical history, physical examination, vital signs, 12-lead ECG, hematology, biochemistry, coagulation, and urinalysis
• Forced expiratory volume in 1 second (FEV1) of at least 80% of predicted value at screening
• Ability and willingness to abstain from alcohol, caffeine, xanthine-containing beverages or food from 48 hours prior to study drug administration until discharge from the clinical unit
• If male, must agree to use a condom and have a non-pregnant female partner of childbearing potential agree to use a highly effective method of contraception
• If female, must be of non-childbearing potential or, if female of childbearing potential, a willingness to abstain from sexual activity or agree to use a high effective method of contraception that could lead to pregnancy
• Other inclusion criteria per protocol

Exclusion Criteria:

• History or presence of significant oncologic, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, vascular or neurological disease, including any acute illness or surgery within the past 3 months determined by the Investigator to be clinically relevant
• Recent history (within 6 months) of known or suspected Clostridium difficile infection
• History of seizure disorders
• Positive urine drug, alcohol or cotinine testing at screening or check-in (Day -1)
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HCV Ab)
• Positive testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening or prior to first dosing

• Presence of the following symptoms at screening or within 28 days prior to screening or check-in (Day -1):

  1. Fever, chills or sweats (temperature of 38 °C / 100.4 °F or higher)
  2. Difficulty breathing
  3. Cough
  4. Sore throat
  5. New or recent loss of taste or smell
  6. Nausea, vomiting or diarrhea
• Close contact with anyone who tested positive for SARS-CoV-2 infection within 28 days prior to screening or check-in (Day -1)
• Electrocardiogram (ECG) with QTcF interval duration equal or greater than 450 msec for males and 470 msec for females

• Subjects who have any of the following abnormalities on laboratory values at screening or Check-In including:

  1. White blood cell count < 3,000/mm3, hemoglobin < 11g/dL
  2. Absolute neutrophil count ≤ 2,000/mm3, platelet count <120,000/mm3
  3. alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) greater than the upper limit of normal (ULN) for the reference laboratory
• History of substance abuse or alcohol abuse
• Use of prescription medicine & tobacco/nicotine or marijuana-containing products
• A female who is pregnant or breastfeeding
• Other exclusion criteria per protocol

Contacts and Locations

Locations

United Kingdom

Medical Facility

Manchester, United Kingdom, M23 9QZ

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: NCT04868292
• Other Study ID Numbers: SPR206-102; CDMRP-JW180095-A ( Other Grant/Funding Number: United States Department of Defense ); 2020-006019-52 ( EudraCT Number )
• First Posted: April 30, 2021
• Last Update Posted: November 17, 2021
• Last Verified: November 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:

pharmacokinetics; alveolar macrophages (AM); epithelial lining fluid (ELF); intrapulmonary; bronchoalveolar lavage