ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12622001387718

Ethics application status

Approved

Date submitted

4/10/2022

Date registered

28/10/2022

Date last updated

28/01/2024

Date data sharing statement initially provided

28/10/2022

Type of registration

Prospectively registered

Titles & IDs

Public title

A first-in-human study to investigate subcutaneous doses of SAR444559 compared with placebo in healthy adult participants.

Scientific title

A randomized, double-blind, placebo-controlled, phase 1, single centre, First-in-human, two-part study to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single (SAD17442) and multiple (MAD17443) ascending, subcutaneous doses of SAR444559 in healthy adult participants.

Secondary ID [1]

SAD17442-MAD17443

Universal Trial Number (UTN)

U1111-1278-4028

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Autoimmune disorder

Condition category

Condition code

Inflammatory and Immune System

Autoimmune diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Part 1:
SAR444559: Single dose administration of SAR444559 on Day 1, of approximatively 9 single ascending dose levels. The starting dose will be 0.03 mg.

Treatment duration will be 7 weeks, including a 4-day in-house institutionalisation period after single dose administration and a follow-up period up to the end of study (EOS) visit.

Mode of administration: Subcutaneous (SC) injection administered by the clinical study site staff in the clinical study center. The dose increment factors for dose escalation will be based on the observed cell depletion and may be adjusted following emerging safety and tolerability.

Part 2:
SAR444559: Multiple dose administrations of SAR444559 every 2 weeks (Q2W) on days 1, 15, and 29, of up to 3 ascending repeated dose levels.
The starting dose of part 2 will be determined upon review of adverse event, PK and PD data from Part 1 by a safety review committee. The dose increment factors for dose escalation will be based on the observed cell depletion and may be adjusted following emerging safety, tolerability.

Treatment duration will be approximately 11 weeks including 4-day in-house institutionalisation periods after each dose administration (3 total doses) and follow-up periods between and after each of the three institutionalizations up to the end of study (EOS) visit. Mode of administration: SC injections administered by the clinical study site staff in the clinical study centre.

Participants in part 1 and part 2 are recruited independently, and part 2 will be undertaken in unique participant cohorts.

The strategies used to monitor adherence to and/or fidelity of the intervention will include supervised administration at site, appropriate record of each administration information, and double confirmation of the dosing by another member of the study site staff other than the one administrating the study intervention.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Part 1:
Placebo: Single dose administration of matching placebo dosages, SC injection.
The composition of the placebo treatment: Histidine 20 mM, sucrose 8 % w/v, PS80 0.08 % w/v, pH 6.0
Part 2:
Placebo: Multiple dose administration of matching placebo dosages, SC injections.
The composition of the placebo treatment: Histidine 20 mM, sucrose 8 % w/v, PS80 0.08 % w/v, pH 6.0

Control group

Placebo

Outcomes

Primary outcome [1]

Number of participants with adverse events (AEs) /treatment-emergent adverse events (TEAEs): by assessment of vital signs (heart rate [pulse oximeter], systolic and diastolic blood pressure [in a seated and standing position using an automated BP monitor], body temperature [using an ear thermometer], respiratory rate [pulse oximeter]), clinical laboratory evaluations (haematology, liver function, renal function, serology for hepatitis, vaccine titres) assessed using blood samples, and 12-lead ECG.

Timepoint [1]

Part 1: Baseline up to end of study (Day 50)
- Vital signs assessed at Baseline, 24, 48, 72, 96, 168, 240, 336, 504, 672, 840, 1008, 1176 hours post-single dose
- Blood samples collected at Baseline, 24, 72, 96, 168, 336, 672, 1008, 1176 hours post-dose
- 12-lead ECG performed at Baseline, 24, 48, 72, 96, 168, 336, 672, 1176 hours post-dose

Part 2: Baseline up to end of study (Day 78)
- Vital signs assessed at Baseline, and 24, 48, 72, 168 and 312 hours post first dose. 0 hours (prior to second dose), and 24, 48, 72, 168, 312 hours after second dose. 0 hours (prior to third dose), and 24, 48, 72, 168, 336, 504, 672, 840 and 1176 hours after third dose.
- Blood samples collected the day before Baseline, at Baseline, and 24, 72, 168 and 312 hours post first dose. 1 day prior to second dose, and 24, 72 and 312 hours after second dose. 1 day before third dose, 24, 72, 336, 672 and 1176 after third dose
- 12-lead ECG performed at Baseline, 48 and 72 hours post first dose. 0 hours prior to second dose, and 48 and 72 hours after second dose. 0 hours prior to third dose, and 48, 72, 336, 672 and 1176 hours after third dose.

Primary outcome [2]

Comprehensive ophthalmic examination outcomes: Assessment of eye lid, cornea, iris, lens, anterior chamber, vitreous body, retina, macula, optic nerve, fraction, visual acuity, intraocular pressure. Methods used for the assessment/measurement include Uncorrected or CVA with patient glasses, Standard Luminance EDTRS BCVA, Goldmann Applanation Tonometry, Gonioscopy, Anterior Segment OCT and IOL Master, SD-OCT and OPTOS, Slit lamp biomicrospcopy, dilated ophthalmoscopy, Posterior Segment US (B Scan).

Timepoint [2]

Primary outcome [3]

Timepoint [3]

Part 1: Baseline up to end of study (Day 50)
Ophthalmologic examination at: Baseline, 48, 168 and 1176 hours post single dose, as well as at any time (in case of) the participant experiences ocular signs or symptoms, including, eg, blurred vision, narrowed vision (tunnel vision) or blind spots, discomfort, eye pain or pressure with or without headache/nausea/vomiting, loss of vision, red eyes, dry eyes.
Part 2: Baseline up to end of study (Day 78)
Ophthalmologic examination at: Baseline, 48 hours post first dose, 48 hours after second dose, 48 and 1176 hours after third dose, as well as at any time (in case of) the participant experiences ocular signs or symptoms, including, eg, blurred vision, narrowed vision (tunnel vision) or blind spots, discomfort, eye pain or pressure with or without headache/nausea/vomiting, loss of vision, red eyes, dry eyes.

Secondary outcome [1]

Assessment of pharmacokinetic (PK) parameters using blood samples: at least Cmax, Tmax, AUClast, AUC (part 1) and AUC0-tau (part 2)

Timepoint [1]

Part 1: Baseline up to end of study (Day 50)
Blood samples collected at: Baseline, 24, 48, 72, 96, 168, 240, 336, 504, 672, 840, 1008 and 1176 hours post single dose.

Part 2: Baseline up to end of study (Day 78)
Blood samples collected at: Baseline, and 24, 48, 72 and 168 hours post first dose. 0 hours prior to second dose, and 72 hours after second dose. 0 hours prior to third dose, and 24, 48, 72, 168, 336, 504, 672, 840, 1176 hours after third dose.

Secondary outcome [2]

Anti-SAR444559 antibodies using blood samples

Timepoint [2]

Part 1: Baseline up to end of study (Day 50)
Blood samples will be collected: at Baseline, and 168, 672, 1176 hours post single dose.

Part 2: Baseline up to end of study (Day 78)
Blood samples will be collected: at Baseline and 168 hours post first dose, 0 hours prior to third dose, and 336 and 1176 hours after third dose.

Secondary outcome [3]

Exploratory:
Assessment of PD parameters using blood samples: CD38 expressing white blood cells measured by Fluorescence activated cell shortening (FACS)

Timepoint [3]

Part 1: Baseline up to end of study (Day 50)
Blood samples will be collected: at Baseline, and 24, 48, 96, 168, 336, 672 and 1176 hours after single dose.
Part 2: Baseline up to end of study (Day 78)
Blood samples will be collected: at Baseline, and 24 hours after first dose, 0 hours prior to second dose, and 0 hours prior to third dose and 24, 336, 672 and 1176 hours after third dose.

Eligibility

Key inclusion criteria

Participants who are overtly healthy as determined by medical evaluation including medical/surgical history, physical examination, laboratory tests, and cardiac monitoring.
Body weight within 50 to 100 kg and body mass index (BMI) within the range 18 to 32 kg/m2 (inclusive).
A female participant not pregnant or breastfeeding, and one of the following conditions applies:
-- Is a woman of non-child-bearing potential (WONCBP) or
-- Is a woman of child-bearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective
Male participants who agree to refrain from donating and cryopreservating sperm

Minimum age

18 Years

Maximum age

55 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
-History or presence of cardiovascular, respiratory (excluding fully resolved childhood asthma with no history of hospitalization), hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
- Significant ocular disease including but not limited to any history of glaucoma, any retinal pathology or history of retinal issues including retinal tears/holes/detachment, history of ocular inflammation/uveitis, moderate/severe refractive errors, pathologic gonioscopy result, and shallow anterior chamber.
-Live vaccines: Last administration of a vaccine within 3 months before randomization.

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)

Randomization lists for each study part are generated by Sanofi and will be provided to the unblinded pharmacist. The open randomization list will be filed in a sealed envelope with tamper-proof adhesive tape and stored at the pharmacy. The study interventions will be allocated in accordance with those lists by the unblinded pharmacist. Investigators will remain blinded to each participant’s assigned study intervention throughout the course of the study.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Permuted block randomisation

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

Intervention assignment

Parallel

Other design features

Single-center, randomized, double-blind, parallel group, single and repeated dose escalation study.

Phase

Phase 1

Type of endpoint/s

Safety

Statistical methods / analysis

Recruitment

Recruitment status

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Safety concerns

Date of first participant enrolment

Anticipated

5/12/2022

Actual

6/12/2022

Date of last participant enrolment

Anticipated

15/04/2024

Actual

9/10/2023

Date of last data collection

Anticipated

27/11/2023

Actual

7/12/2023

Sample size

Target

102

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD,VIC

Recruitment hospital [1]

Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston

Recruitment postcode(s) [1]

4007 - Herston

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Sanofi-Aventis R&D

Address [1]

1 avenue Pierre Brossolette
91380 Chilly-Mazarin Cedex

Country [1]

France

Primary sponsor type

Commercial sector/Industry

Name

Sanofi-Aventis Australia Pty Ltd

Address

12-24 Talavera Rd, Macquarie Park, NSW 2113

Country

Australia

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

Sanofi-Aventis R&D

Address [1]

1 avenue Pierre Brossolette
91380 Chilly-Mazarin Cedex

Country [1]

France

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee

Ethics committee address [1]

55 Commercial Rd, Melbourne, VIC 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/10/2022

Approval date [1]

02/11/2022

Ethics approval number [1]

Summary

Brief summary

This is a parallel, randomized, placebo-controlled, two-part, Phase 1, Investigator- and participant blinded, first-in-human (FIH) study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) profiles, and immunogenicity of single (SAD17442) and multiple (MAD17443) ascending, subcutaneous doses of SAR444559 in male and female healthy participants aged 18 to 55 years. 
Part 1 – SAD17442:
-	The study duration per participant will be up to 12 weeks, including screening period. 
-	The treatment duration will be 7 weeks including a 4-day in-house institutionalization period after single dose administration and a follow-up period up to the end of study (EOS) visit.
PD is as assessed as exploratory part of the protocol.
The number of visits will be 10 ambulatory on-site visits and one 4-day in-house period, and 4 to 5 ambulatory visits to the ophthalmologist.
Part 2 – MAD17443:
-	The study duration per participant will be approximately 16 weeks, including screening period and treatment period of 11 weeks. 
-	The treatment duration will be approximately 11 weeks including 4-day in-house institutionalization periods after each dose administration (3 total doses) and follow-up periods between and after each of the three institutionalizations up to the end of study (EOS) visit.
PD is as assessed as exploratory part of the protocol. The number of visits will be 10 ambulatory on-site visits and three 4-day in-house periods, and 4 to 5 ambulatory visits to the ophthalmologist.

Trial website

Trial related presentations / publications

Public notes

Participants not fully vaccinated against COVID-19 according to local guidelines and those having received non-live vaccines including COVID-19 with last administration of a vaccine within 1 month before randomization are excluded from participation in this study

Contacts

Principal investigator

Name

Dr Richard Friend

Address

Level 5 Clive Berghofer Cancer Centre Research Centre,
300 Herston Road, Herston, QLD 4006

Country

Australia

Phone

+610439726233

Fax

[email protected]

Contact person for public queries

Name

Nucleus Network Brisbane

Address

Level 5 Clive Berghofer Cancer Centre Research Centre,
300 Herston Road, Herston, QLD 4006

Country

Australia

Phone

+61 1800 243 733

Fax

[email protected]

Contact person for scientific queries

Name

Richard Friend

Address

Level 5 Clive Berghofer Cancer Centre Research Centre,
300 Herston Road, Herston, QLD 4006

Country

Australia

Phone

+61 7 3707 2720

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Individual participant data of published results only

When will data be available (start and end dates)?

Immediately following publication, no end date defined.

Available to whom?

Case-by-case basis at the discretion of Primary Sponsor.

Available for what types of analyses?

Data to achieve the aims in the approved proposal.

How or where can data be obtained?

Researchers may enquire about the availability of data from Sanofi sponsored clinical trials using the Vivli Enquiry Form (https://vivli.org/members/enquiries-about-studies-not-listed-on-the-vivli-platform/).

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
17251	Clinical study report				Researchers may enquire about the availability of ... [More Details]

Results publications and other study-related documents

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Trial Review

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