Healthy VolunteersPhase 1NCT03792308

A First in Human Study of the Safety and Tolerability of Single and Multiple Doses of SPR206 in Healthy Volunteers

A Phase 1 study testing SPR206 in people with Healthy Volunteers, run by Spero Therapeutics at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to assess the safety, tolerability and pharmacokinetics of single and multiple intravenous doses of SPR206 when administered to healthy adult volunteers. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: SPR206
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 94 participants
Where: 1 siteAustralia
Study dates: 18 Dec 2018to 23 Dec 2019
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy adult males and/or females (of non-childbearing potential), 18 to 55 years of age (inclusive) at the time of screening.
BMI ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive) for all cohorts;
Medically healthy without clinically significant abnormalities at the screening visit or Day -1, including:
Physical examination (PE) and vital signs including temperature, pulse, respiratory rate, and blood pressure;
Triplicate electrocardiograms (ECGs) taken at least 1 minute apart with QTcF interval duration less than 450 msec obtained as an average from the triplicate screening and pre-dose Day 1 ECGs after at least 5 min in a semi-supine quiet rest;
Hemoglobin/hematocrit, white blood cell (WBC) count, and platelet count equal to or greater than the lower limit of normal range of the reference laboratory;

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Serum creatinine and bilirubin (total and conjugated) equal equal to or less than the upper limit of normal for the reference laboratory. Serum urea, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) equal to or less than 1.5 times the upper limit of normal for the reference laboratory; results of all other clinical chemistry and urine analytes without any clinically significant abnormality.
Discussion between the PI and the Medical Monitor (MM) is encouraged regarding the potential significance of any laboratory value that is outside of the normal range during the pre-dose period.
Be non-smokers (including tobacco, e-cigarettes, nicotine patches, or marijuana) for at least 1 month prior to participation in the study;
Willing and able to provide written informed consent;
Be willing and able to comply with all study assessments and adhere to the protocol schedule;
Have suitable venous access for drug administration and blood sampling;
If female, be of non-childbearing potential (e.g. post-menopausal as demonstrated by follicle stimulating hormone (FSH) or surgical sterilization i.e., tubal ligation or hysterectomy). Provision of documentation is not required for female sterilization, verbal confirmation is adequate;
If male, a willingness not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, a willingness to use a condom in addition to having the female partner use a highly effective method of birth control (such as an intrauterine device, diaphragm, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation). This criterion applies to males (and/or female partners) who are surgically sterile and must be followed from the time of first study drug administration until 90 days after the final administration of study drug.
Are fluent in English such that they are able to understand the informed consent form written in English and do not require use of an interpreter.

Who cannot join

History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past three months determined by the PI to be clinically relevant;
History of known or suspected Clostridium difficile infection;
History of seizure disorders;
Positive urine drug/alcohol 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);
History of substance abuse or alcohol abuse (defined as greater than 2 standard drinks on average each and every day, where 1 standard drink is defined as containing 10 g of alcohol and is equivalent to 1 can or stubby of mid-strength beer, 30 ml nip spirits, or 100 ml wine) within the previous 5 years;

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Use of any prescription medication or any over-the-counter medication, herbal products, vitamins, diet aids or hormone supplements within 7 days prior to randomisation;
Documented hypersensitivity reaction or anaphylaxis to any medication;
Donation of blood or plasma within 30 days prior to randomisation, or loss of whole blood of more than 500 mL within 30 days prior to randomisation, or receipt of a blood transfusion within 1 year of study enrollment;
Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study);
Any other condition or prior therapy, which, in the opinion of the PI, would make the volunteer unsuitable for this study, including unable to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.
Participants in Cohort 13 should not have participated in any previous cohort of this study.

Trial locations and contacts

1 site in 1 country.

Australia1 site

Scientia Clinical Research Ltd.
Randwick, New South Wales, 2031

Other trials in Australia

About this study

Official title: A Phase 1, Two-part, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of SPR206 in Healthy Volunteers

The purpose of this study is to assess the safety, tolerability and pharmacokinetics of single and multiple intravenous doses of SPR206 when administered to healthy adult volunteers.

Read the detailed description

This Phase 1 First in Human study is designed to assess the safety, tolerability, and pharmacokinetics of single and multiple intravenous doses of SPR206 when administered to healthy adult volunteers. This is a randomized, double-blind, placebo-controlled, ascending dose, multi-cohort trial. A total of 104 healthy volunteers will be enrolled in 13 cohorts. The study will be conducted in two phases: A single ascending dose (SAD) phase, followed by a multiple ascending dose (MAD) phase. In SAD, participants in Cohorts 1 - 8 will receive one dose of SPR206 or placebo. In MAD, participants in Cohorts 9 - 12 will receive multiple doses of SPR206 or placebo for 7 consecutive days, and a final cohort, Cohort 13, will receive multiple doses of SPR206 or placebo for 14 consecutive days at a dose deemed safe and tolerable and not to exceed the maximum dose administered to participants in Cohorts 9 - 12. In both parts sequential cohorts will be exposed to increasing doses of SPR206.

Conditions: Healthy Volunteers
Being tested: SPR206, Placebo
Keywords: Safety, Tolerability, Pharmacokinetics, SPR206

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SPR206Drug
SAD Cohorts: Double-blind dosing will occur in Cohorts 1 - 8. Six participants will receive single doses of SPR206. The dose escalation steps may be altered following review of the safety data upon completion of each cohort.
MAD Cohorts: Double blind dosing will occur in Cohorts 9 - 13. Six participants in each cohort will receive multiple doses of SPR206. The dose escalation steps may be altered following review of the safety data upon completion of each cohort. Dosing will commence on the morning of Day 1. Three doses will be administered per day at approximately 8 hours apart. Daily dosing will continue for a total of 7 consecutive days for Cohorts 9 - 12 and for a total of 14 consecutive days for Cohort 13.
PlaceboDrug
Also called 0.9% sodium chloride for injection
0.9% sodium chloride for injection. SAD Cohorts: Two participants in each cohort will receive matching placebo. MAD Cohorts: Two participants in each cohort will receive matching placebo.

Study groups in NCT03792308
Study group	Role	What they receive
SPR206	Experimental	SAD Cohorts: Subjects will receive single doses of SPR206 via IV infusion over one hour. Planned doses to be studied are: 10, 25, 50, 100, 200, 300, 350 and 400mg. If the 300 mg dose is not deemed safe and well-tolerated, a dose of 250 mg will be used. MAD Cohorts: Subjects will receive SPR206 via IV infusion over one hour q8h for 7 consecutive days (Cohorts 9 - 12) and over one hour q8h for 14 consecutive days (Cohort 13). Up to five dose groups will be studied. Planned doses will be 25 mg, 50 mg, 100 mg and 150 mg with dosing occurring q8h for 7 consecutive days (Cohorts 9 - 12) and q8h for 14 consecutive days (Cohort 13). Cohort 13 participants will be dosed at a dose deemed safe and tolerable, not to exceed the maximum dose tested in previous MAD dose cohorts. . Receives: Drug: SPR206
Placebo	Placebo comparator	The placebo used during this study is normal saline (0.9% sodium chloride for injection). SAD Cohorts: Subjects will receive single infusions of placebo (0.9% sodium chloride for injection) over one hour. MAD Cohorts: Subjects will receive q8h infusions of placebo over 1 hour for 7 consecutive days (Cohorts 9 - 12) and q8h infusions of placebo over 1 hour for 14 consecutive days (Cohort 13). Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Treatment emergent adverse events assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion [Safety and Tolerability]
This outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatment
Measured: SAD: Up to 7 days; MAD: Up to 21 days for Cohorts 9 - 12 and up to 28 days for Cohort 13.

Secondary outcomes (27)

Pharmacokinetics: Time to maximum concentration (Tmax)
Plasma sample collection for pharmacokinetic analysis
Measured: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Time to maximum concentration (Tmax)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1:pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3 and 5 (Cohorts 9 - 12) and prior to morning dose on Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Time to maximum concentration (Tmax)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Maximum concentration (Cmax)
Plasma sample collection for pharmacokinetic analysis
Measured: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Maximum concentration (Cmax)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 for Cohorts 9 - 12 and on Days 2, 3, 5, 7, 9, 11, and 13 for Cohort 13.
Pharmacokinetics: Maximum concentration (Cmax)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 7 (Cohorts 9 -12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Plasma sample collection for pharmacokinetic analysis
Measured: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Plasma sample collection for pharmacokinetic analysis
Measured: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 for Cohorts 9 - 12 and Days 2, 3, 5, 7, 9, 11, and 13 for Cohort 13.
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.
Pharmacokinetics: Terminal Elimination Rate Constant (kel)
Plasma sample collection for pharmacokinetic analysis
Measured: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Terminal Elimination Rate Constant (kel)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Terminal Elimination Rate Constant (kel)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Terminal half-life (t1/2)
Plasma sample collection for pharmacokinetic analysis
Measured: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Terminal half-life (t1/2)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Terminal half-life (t1/2)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.
Pharmacokinetics: Terminal clearance (CL)
Plasma sample collection for pharmacokinetic analysis
Measured: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Terminal clearance (CL)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Terminal clearance (CL)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Volume of distribution (Vd)
Plasma sample collection for pharmacokinetic analysis
Measured: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Volume of distribution (Vd)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Volume of distribution (Vd)
Plasma sample collection for pharmacokinetic analysis
Measured: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.
Pharmacokinetics: SPR206 excreted in urine in each collection interval
Urine sample collection for measurement of SPR206 excreted in urine over 24 hours.
Measured: SAD: Urine samples collected at pre-dose and over the intervals of 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 hours after start of infusion.
Pharmacokinetics: SPR206 excreted in urine in each collection interval
Urine sample collection for measurement of SPR206 excreted in urine over 24 hours.
Measured: MAD: Urine samples collected on Day 1 pre-dose, 0-4 hours and 4-8 hours after start of first infusion. Days 7-8 (Cohorts 9 - 12): 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours after start of infusion.
Pharmacokinetics: SPR206 excreted in urine in each collection interval
Urine sample collection for measurement of SPR206 excreted in urine over 24 hours.
Measured: MAD: Urine samples collected on Day 1 pre-dose, 0-4 hours and 4-8 hours after start of first infusion. Days 14-15 (Cohort 13): 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours after start of infusion.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Dec 201823 Dec 2019

First posted3 Jan 2019
Study start18 Dec 2018
Primary completion23 Dec 2019
Study completion23 Dec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized, double-blind, placebo-controlled, combined single and multiple ascending dose (SAD and MAD) trial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 94 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03792308
Sponsor's protocol ID: SPR206-101
Status last verified: Jan 2020
First submitted: 17 Dec 2018
Last updated: 10 Jan 2020
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Bruss J, Lister T, Gupta VK, Stone E, Morelli L, Lei Y, Melnick D. Single- and Multiple-Ascending-Dose Study of the Safety, Tolerability, and Pharmacokinetics of the Polymyxin Derivative SPR206. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0073921. doi: 10.1128/AAC.00739-21. Epub 2021 Aug 2.
PubMed 34339267

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Two-part, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of SPR206 in Healthy Volunteers
ClinicalTrials.gov ID: NCT03792308
Acronym / sponsor ID: SPR206-101
Conditions: Healthy Volunteers
Keywords: Safety, Tolerability, Pharmacokinetics, SPR206
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 94 participants (actual)
Lead sponsor: Spero TherapeuticsIndustry (pharma, biotech, devices)
Collaborators: Clinical Network Services (CNS) Pty Ltd
Study start: 18 Dec 2018 (actual)
Primary completion: 23 Dec 2019 (actual)
Study completion: 23 Dec 2019 (actual)
First posted: 3 Jan 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to assess the safety, tolerability and pharmacokinetics of single and multiple intravenous doses of SPR206 when administered to healthy adult volunteers.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Randomized, double-blind, placebo-controlled, combined single and multiple ascending dose (SAD and MAD) trial

Arm	Type	Receives
SPR206	Experimental	Drug: SPR206SAD Cohorts: Subjects will receive single doses of SPR206 via IV infusion over one hour. Planned doses to be studied are: 10, 25, 50, 100, 200, 300, 350 and 400mg. If the 300 mg dose is not deemed safe and well-tolerated, a dose of 250 mg will be used. MAD Cohorts: Subjects will receive SPR206 via IV infusion over one hour q8h for 7 consecutive days (Cohorts 9 - 12) and over one hour q8h for 14 consecutive days (Cohort 13). Up to five dose groups will be studied. Planned doses will be 25 mg, 50 mg, 100 mg and 150 mg with dosing occurring q8h for 7 consecutive days (Cohorts 9 - 12) and q8h for 14 consecutive days (Cohort 13). Cohort 13 participants will be dosed at a dose deemed safe and tolerable, not to exceed the maximum dose tested in previous MAD dose cohorts. .
Placebo	Placebo comparator	Drug: PlaceboThe placebo used during this study is normal saline (0.9% sodium chloride for injection). SAD Cohorts: Subjects will receive single infusions of placebo (0.9% sodium chloride for injection) over one hour. MAD Cohorts: Subjects will receive q8h infusions of placebo over 1 hour for 7 consecutive days (Cohorts 9 - 12) and q8h infusions of placebo over 1 hour for 14 consecutive days (Cohort 13).

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (15 listed)

Healthy adult males and/or females (of non-childbearing potential), 18 to 55 years of age (inclusive) at the time of screening.
BMI ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive) for all cohorts;
Medically healthy without clinically significant abnormalities at the screening visit or Day -1, including:
Discussion between the PI and the Medical Monitor (MM) is encouraged regarding the potential significance of any laboratory value that is outside of the normal range during the pre-dose period.
Be non-smokers (including tobacco, e-cigarettes, nicotine patches, or marijuana) for at least 1 month prior to participation in the study;

Key exclusion criteria (12 listed)

History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past three months determined by the PI to be clinically relevant;
History of known or suspected Clostridium difficile infection;
History of seizure disorders;
Positive urine drug/alcohol 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);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SPR206SAD Cohorts: Double-blind dosing will occur in Cohorts 1 - 8. Six participants will receive single doses of SPR206. The dose escalation steps may be altered following review of the safety data upon completion of each cohort. MAD Cohorts: Double blind dosing will occur in Cohorts 9 - 13. Six participants in each cohort will receive multiple doses of SPR206. The dose escalation steps may be altered following review of the safety data upon completion of each cohort. Dosing will commence on the morning of Day 1. Three doses will be administered per day at approximately 8 hours apart. Daily dosing will continue for a total of 7 consecutive days for Cohorts 9 - 12 and for a total of 14 consecutive days for Cohort 13.	Drug	SPR206
PlaceboAlso: 0.9% sodium chloride for injection0.9% sodium chloride for injection. SAD Cohorts: Two participants in each cohort will receive matching placebo. MAD Cohorts: Two participants in each cohort will receive matching placebo.	Drug	Placebo

Primary outcome

Treatment emergent adverse events assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion [Safety and Tolerability]
Time frame: SAD: Up to 7 days; MAD: Up to 21 days for Cohorts 9 - 12 and up to 28 days for Cohort 13.
This outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatment

27 secondary outcomes

Pharmacokinetics: Time to maximum concentration (Tmax)
Time frame: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Time to maximum concentration (Tmax)
Time frame: MAD: Day 1:pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3 and 5 (Cohorts 9 - 12) and prior to morning dose on Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Time to maximum concentration (Tmax)
Time frame: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Maximum concentration (Cmax)
Time frame: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Maximum concentration (Cmax)
Time frame: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 for Cohorts 9 - 12 and on Days 2, 3, 5, 7, 9, 11, and 13 for Cohort 13.
Pharmacokinetics: Maximum concentration (Cmax)
Time frame: MAD: Day 7 (Cohorts 9 -12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Time frame: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Time frame: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Time frame: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Time frame: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Time frame: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 for Cohorts 9 - 12 and Days 2, 3, 5, 7, 9, 11, and 13 for Cohort 13.
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Time frame: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.
Pharmacokinetics: Terminal Elimination Rate Constant (kel)
Time frame: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Terminal Elimination Rate Constant (kel)
Time frame: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Terminal Elimination Rate Constant (kel)
Time frame: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Terminal half-life (t1/2)
Time frame: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Terminal half-life (t1/2)
Time frame: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Terminal half-life (t1/2)
Time frame: MAD: Day 1 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.
Pharmacokinetics: Terminal clearance (CL)
Time frame: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Terminal clearance (CL)
Time frame: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Terminal clearance (CL)
Time frame: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.
Pharmacokinetics: Volume of distribution (Vd)
Time frame: SAD: Days 1 and 2 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8, 12 and 24 hours post-infusion start.
Pharmacokinetics: Volume of distribution (Vd)
Time frame: MAD: Day 1 at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, and 8 hours post morning infusion start. Prior to morning dose on Days 2, 3, and 5 (Cohorts 9 - 12) and Days 2, 3, 5, 7, 9, 11, and 13 (Cohort 13).
Pharmacokinetics: Volume of distribution (Vd)
Time frame: MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.
Pharmacokinetics: SPR206 excreted in urine in each collection interval
Time frame: SAD: Urine samples collected at pre-dose and over the intervals of 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 hours after start of infusion.
Pharmacokinetics: SPR206 excreted in urine in each collection interval
Time frame: MAD: Urine samples collected on Day 1 pre-dose, 0-4 hours and 4-8 hours after start of first infusion. Days 7-8 (Cohorts 9 - 12): 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours after start of infusion.
Pharmacokinetics: SPR206 excreted in urine in each collection interval
Time frame: MAD: Urine samples collected on Day 1 pre-dose, 0-4 hours and 4-8 hours after start of first infusion. Days 14-15 (Cohort 13): 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours after start of infusion.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2020.
Derived from this study: PubMed 34339267Bruss J, Lister T, Gupta VK, Stone E, Morelli L, Lei Y, Melnick D. Single- and Multiple-Ascending-Dose Study of the Safety, Tolerability, and Pharmacokinetics of the Polymyxin Derivative SPR206. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0073921. doi: 10.1128/AAC.00739-21. Epub 2021 Aug 2.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James Kuo, MBBS, B Med Sci, FRACP principal investigator

Scientia Clinical Research Limited

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SPR206 in people with Healthy Volunteers, run by Spero Therapeutics at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment emergent adverse events assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion [Safety and Tolerability] (time frame: SAD: Up to 7 days; MAD: Up to 21 days for Cohorts 9 - 12 and up to 28 days for Cohort 13.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03792308, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2020.