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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03792308




Registration number
NCT03792308
Ethics application status
Date submitted
17/12/2018
Date registered
3/01/2019
Date last updated
26/07/2019

Titles & IDs
Public title
A First in Human Study of the Safety and Tolerability of Single and Multiple Doses of SPR206 in Healthy Volunteers
Scientific 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
Secondary ID [1] 0 0
SPR206-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SPR206
Treatment: Drugs - Placebo

Experimental: SPR206 - 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.
.

Placebo Comparator: Placebo - 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).


Treatment: Drugs: SPR206
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.

Treatment: Drugs: Placebo
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
SAD: Up to 7 days; MAD: Up to 21 days for Cohorts 9 - 12 and up to 28 days for Cohort 13.
Secondary outcome [1] 0 0
Pharmacokinetics: Time to maximum concentration (Tmax) - Plasma sample collection for pharmacokinetic analysis
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Pharmacokinetics: Time to maximum concentration (Tmax) - Plasma sample collection for pharmacokinetic analysis
Timepoint [2] 0 0
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).
Secondary outcome [3] 0 0
Pharmacokinetics: Time to maximum concentration (Tmax) - Plasma sample collection for pharmacokinetic analysis
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Pharmacokinetics: Maximum concentration (Cmax) - Plasma sample collection for pharmacokinetic analysis
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Pharmacokinetics: Maximum concentration (Cmax) - Plasma sample collection for pharmacokinetic analysis
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Pharmacokinetics: Maximum concentration (Cmax) - Plasma sample collection for pharmacokinetic analysis
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t) - Plasma sample collection for pharmacokinetic analysis
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t) - Plasma sample collection for pharmacokinetic analysis
Timepoint [8] 0 0
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).
Secondary outcome [9] 0 0
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t) - Plasma sample collection for pharmacokinetic analysis
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf) - Plasma sample collection for pharmacokinetic analysis
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf) - Plasma sample collection for pharmacokinetic analysis
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf) - Plasma sample collection for pharmacokinetic analysis
Timepoint [12] 0 0
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.
Secondary outcome [13] 0 0
Pharmacokinetics: Terminal Elimination Rate Constant (kel) - Plasma sample collection for pharmacokinetic analysis
Timepoint [13] 0 0
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.
Secondary outcome [14] 0 0
Pharmacokinetics: Terminal Elimination Rate Constant (kel) - Plasma sample collection for pharmacokinetic analysis
Timepoint [14] 0 0
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).
Secondary outcome [15] 0 0
Pharmacokinetics: Terminal Elimination Rate Constant (kel) - Plasma sample collection for pharmacokinetic analysis
Timepoint [15] 0 0
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.
Secondary outcome [16] 0 0
Pharmacokinetics: Terminal half-life (t1/2) - Plasma sample collection for pharmacokinetic analysis
Timepoint [16] 0 0
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.
Secondary outcome [17] 0 0
Pharmacokinetics: Terminal half-life (t1/2) - Plasma sample collection for pharmacokinetic analysis
Timepoint [17] 0 0
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).
Secondary outcome [18] 0 0
Pharmacokinetics: Terminal half-life (t1/2) - Plasma sample collection for pharmacokinetic analysis
Timepoint [18] 0 0
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.
Secondary outcome [19] 0 0
Pharmacokinetics: Terminal clearance (CL) - Plasma sample collection for pharmacokinetic analysis
Timepoint [19] 0 0
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.
Secondary outcome [20] 0 0
Pharmacokinetics: Terminal clearance (CL) - Plasma sample collection for pharmacokinetic analysis
Timepoint [20] 0 0
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).
Secondary outcome [21] 0 0
Pharmacokinetics: Terminal clearance (CL) - Plasma sample collection for pharmacokinetic analysis
Timepoint [21] 0 0
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.
Secondary outcome [22] 0 0
Pharmacokinetics: Volume of distribution (Vd) - Plasma sample collection for pharmacokinetic analysis
Timepoint [22] 0 0
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.
Secondary outcome [23] 0 0
Pharmacokinetics: Volume of distribution (Vd) - Plasma sample collection for pharmacokinetic analysis
Timepoint [23] 0 0
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).
Secondary outcome [24] 0 0
Pharmacokinetics: Volume of distribution (Vd) - Plasma sample collection for pharmacokinetic analysis
Timepoint [24] 0 0
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.
Secondary outcome [25] 0 0
Pharmacokinetics: SPR206 excreted in urine in each collection interval - Urine sample collection for measurement of SPR206 excreted in urine over 24 hours.
Timepoint [25] 0 0
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.
Secondary outcome [26] 0 0
Pharmacokinetics: SPR206 excreted in urine in each collection interval - Urine sample collection for measurement of SPR206 excreted in urine over 24 hours.
Timepoint [26] 0 0
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.
Secondary outcome [27] 0 0
Pharmacokinetics: SPR206 excreted in urine in each collection interval - Urine sample collection for measurement of SPR206 excreted in urine over 24 hours.
Timepoint [27] 0 0
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.

Eligibility
Key inclusion criteria
1. Healthy adult males and/or females (of non-childbearing potential), 18 to 55 years of
age (inclusive) at the time of screening.

2. BMI = 18.5 and = 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive) for all
cohorts;

3. Medically healthy without clinically significant abnormalities at the screening visit
or Day -1, including:

1. Physical examination (PE) and vital signs including temperature, pulse,
respiratory rate, and blood pressure;

2. 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;

3. 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;

4. 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.

4. Be non-smokers (including tobacco, e-cigarettes, nicotine patches, or marijuana) for
at least 1 month prior to participation in the study;

5. Willing and able to provide written informed consent;

6. Be willing and able to comply with all study assessments and adhere to the protocol
schedule;

7. Have suitable venous access for drug administration and blood sampling;

8. 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;

9. 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.

10. 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.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 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;

2. History of known or suspected Clostridium difficile infection;

3. History of seizure disorders;

4. Positive urine drug/alcohol testing at screening or check-in (Day -1);

5. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen
(HBsAg) or hepatitis C antibodies (HCV);

6. 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;

7. 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;

8. Documented hypersensitivity reaction or anaphylaxis to any medication;

9. 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;

10. 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);

11. 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.

12. Participants in Cohort 13 should not have participated in any previous cohort of this
study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Scientia Clinical Research Ltd. - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Spero Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Clinical Network Services (CNS) Pty Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT03792308
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James Kuo, MBBS, B Med Sci, FRACP
Address 0 0
Scientia Clinical Research Limited
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Lisa Morelli
Address 0 0
Country 0 0
Phone 0 0
603-264-1008
Fax 0 0
Email 0 0
lmorelli@sperotherapeutics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03792308