We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03022175




Registration number
NCT03022175
Ethics application status
Date submitted
16/12/2016
Date registered
16/01/2017
Date last updated
5/10/2017

Titles & IDs
Public title
A First in Human Study of the Safety and Tolerability of Single and Multiple Doses of SPR741 in Healthy Volunteers
Scientific title
A Two-part, Double-blind, Placebo-controlled, Phase I Study of the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of SPR741 in Healthy Volunteers
Secondary ID [1] 0 0
SPR741-101s
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 - SPR741
Treatment: Drugs - Placebo

Experimental: SPR741 - SPR741 is a novel chemical entity known as a potentiator that specifically interacts with the outer membrane of Gram-negative bacteria to increase the membrane's permeability. This increase in permeability allows Gram-positive antibiotics to enter and kill the cell.
SAD cohorts: Subjects will receive single doses of SPR741 over 60 minute IV infusion. Planned doses to be studied are 5, 15, 50, 100, 200, 400, 600 and 800 mg.
MAD cohorts: Subjects will receive SPR741 over 60 minute IV infusion three times a day (TID). Four dose groups will be studied. Doses will be determined by assessing SAD cohort data.

Placebo Comparator: Placebo - The placebo used during this study is normal saline (0.9% sodium chloride for injection).
SAD: Subjects will receive single infusions of placebo (0.9% sodium chloride for injection) over 60 minutes.
MAD: Subjects will receive TID infusions of placebo over 60 minutes for 14 days


Treatment: Drugs: SPR741
SAD: Double-blind dosing will occur in cohorts 1 through 8. Six participants will receive single doses of SPR741. The dose escalation steps may be altered following review of the safety data upon completion of each cohort.
MAD: The Safety Management Group will evaluate the safety and tolerability data obtained for the participants in Cohorts 1-5 to determine the appropriate dose level of intravenous q8h dosing of SPR741 to be utilized in the first cohort (Cohort 9) in the MAD. 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 14 consecutive days.

Treatment: Drugs: Placebo
0.9% sodium chloride for injection. SAD: Two participants in each cohort will receive matching placebo. MAD: 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
Safety measures: adverse events - The frequency and type of adverse events
Timepoint [1] 0 0
SAD: 5 to 7 days MAD: 21 to 23 days
Primary outcome [2] 0 0
Safety measures: clinical laboratory testing - Clinical laboratory testing - change from baseline to end of study visit
Timepoint [2] 0 0
SAD: Day -1 to day 7; MAD: Day -1 to day 21
Primary outcome [3] 0 0
Safety measures: pulse rate - Change from baseline to end of study visit
Timepoint [3] 0 0
SAD: Day -1 to day 7; MAD: Day -1 to day 21
Primary outcome [4] 0 0
Safety measures: EKG - Change from baseline to end of study visit
Timepoint [4] 0 0
SAD: 5 to 7 days MAD: 21 to 23 days
Primary outcome [5] 0 0
Safety measures: respiratory rate - Change from baseline to end of study visit
Timepoint [5] 0 0
SAD: Day -1 to day 7; MAD: Day -1 to day 21
Primary outcome [6] 0 0
Safety measures: blood pressure - Change from baseline to end of study visit
Timepoint [6] 0 0
SAD: Day -1 to day 7; MAD: Day -1 to day 21
Secondary outcome [1] 0 0
Individual SPR741 plasma concentration-time curves will be tabulated for each dose cohort. - • Blood draws for PK: pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 90, 150 minutes, 3, 4, 5, 6 and 8 hours following start of infusion (Day 1 (first dose) and Day 14 (last dose)). Five additional blood draws will be obtained at 10, 12, 24, 36 and 48 hours following the start of infusion of the last dose (morning of Day 14).
Timepoint [1] 0 0
Day 1 and Day 14
Secondary outcome [2] 0 0
Geometric means will be calculated for Area Under the Curve (AUC) - Blood draws for PK: pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 90, 150 minutes, 3, 4, 5, 6 and 8 hours following start of infusion (Day 1 (first dose) and Day 14 (last dose)). Five additional blood draws will be obtained at 10, 12, 24, 36 and 48 hours following the start of infusion of the last dose (morning of Day 14).
Timepoint [2] 0 0
Day 1 and Day 14
Secondary outcome [3] 0 0
Geometric means will be calculated for Concentration maximum (Cmax) - Blood draws for PK: pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 90, 150 minutes, 3, 4, 5, 6 and 8 hours following start of infusion (Day 1 (first dose) and Day 14 (last dose)). Five additional blood draws will be obtained at 10, 12, 24, 36 and 48 hours following the start of infusion of the last dose (morning of Day 14).
Timepoint [3] 0 0
Day 1 and Day 14
Secondary outcome [4] 0 0
Geometric means will be calculated for Area Under the Curve (AUC) Urine - • Urine collection for PK: pre-dose Day 1 sample, total collection over 0-4, 4-8 hours following start of infusion of first dose on Day 1; then total collection over 0-4, 4-8, 8-12, 12-24 and 24-48 hours following start of infusion of the last dose (Day 14).
Timepoint [4] 0 0
Day 1 and Day 14
Secondary outcome [5] 0 0
Geometric means will be calculated for Concentration maximum (Cmax) Urine - • Urine collection for PK: pre-dose Day 1 sample, total collection over 0-4, 4-8 hours following start of infusion of first dose on Day 1; then total collection over 0-4, 4-8, 8-12, 12-24 and 24-48 hours following start of infusion of the last dose (Day 14).
Timepoint [5] 0 0
Day 1 and Day 14
Secondary outcome [6] 0 0
Mean SPR741 plasma concentration-time curves will be tabulated for each dose cohort. - • Blood draws for PK: pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 90, 150 minutes, 3, 4, 5, 6 and 8 hours following start of infusion (Day 1 (first dose) and Day 14 (last dose)). Five additional blood draws will be obtained at 10, 12, 24, 36 and 48 hours following the start of infusion of the last dose (morning of Day 14).
Timepoint [6] 0 0
Day 1 and Day 14

Eligibility
Key inclusion criteria
1. Healthy adult males and/or females (of non-child bearing 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 62.5 and 100.0 kg (inclusive) for
Cohort 1 only and 55.0 and 100.0 kg (inclusive) for all other cohorts;

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

1. Physical examination, vital signs. Vital signs include temperature, heart rate,
respiratory rate, and blood pressure;

2. Triplicate ECGs without QTcF interval duration greater than 450 msec obtained as
an average from the triplicate screening and pre-dose Day 1 ECGs after at least 5
min in a fully supine quiet rest;

3. Hemoglobin/hematocrit, white blood cell (WBC) count, and platelet count greater
than the lower limit of normal range of the reference laboratory;

4. Creatinine, BUN, ALT and AST equal to or less than 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 SMR is encouraged regarding any abnormal laboratory
value that is outside of the normal range during the pre-dose period.

4. Be non-smokers (including tobacco, e-cigarettes 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
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 30 days after the final
administration of study drug.
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. Positive urine drug/alcohol testing at screening or check-in (Day -1);

4. Positive testing for HIV, HBsAg or HCV;

5. History of substance abuse or alcohol abuse (defined as greater than 2 standard drinks
on average each and every day, where one 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;

6. Use of any prescription medication or any over-the-counter medication, including
herbal products and vitamins within 7 days prior to randomization;

7. Documented hypersensitivity reaction or anaphylaxis to any medication;

8. Donation of blood or plasma within 30 days prior to randomization, or loss of whole
blood of more than 500 mL within 30 days prior to randomization, or receipt of a blood
transfusion within 1 year of study enrollment;

9. Participation in another investigational clinical trial within 30 days prior to Day 1;

10. 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.

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
Completed
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)
SA
Recruitment hospital [1] 0 0
CMAX - A division of IDT Australia, Limited - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

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
CPR Pharma Services Pty Ltd, Australia
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 and tolerability of single and multiple
intravenous doses of SPR741 when administered to healthy adult volunteers.
Trial website
https://clinicaltrials.gov/show/NCT03022175
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nicholas Farinola, MB, BSc, FRACP
Address 0 0
CMAX - A division of IDT Australia, Limited
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications