A Randomized Placebo- and Active Comparator-controlled Study to Evaluate the Photosafety of SAR441566

A Two-part, Randomized Partially-blinded, Parallelgroup, Placebo- and Active Comparatorcontrolled Phase 1 Study to Evaluate the Photosafety of Repeated Oral Dose of SAR441566 in Healthy Adult Participants

This is a single center randomized parallel-group partially-blinded, 4-arm Phase 1 study to evaluate the phototoxic potential of two dose levels of SAR441566 treatment compared to placebo and the active comparator, ciprofloxacin, in healthy adults, 18 to 55 years of age.

There will be two parts:

• Part I is a randomized placebo-controlled trial comparing sensitivity to ultraviolet (UV) light in participants treated with SAR441566 to those treated with placebo.
• Part II is an open label arm consisting of participants treated with ciprofloxacin which induces mild phototoxicity and serves as a positive control.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: SAR441566; Drug: Ciprofloxacin

Detailed Description

The overall duration of the study for each participant will be up to approximately 48 days

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial transparency email recommended (Toll free for US & Canada; Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Study Locations

• United States
  • New Jersey
    • Fair Lawn, New Jersey, United States, 07410
      • TKL Research, Inc. Site Number : 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female participants who are between 18 and 55 years of age, (inclusive), at the time of signing the informed consent
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG.
• Participants with Fitzpatrick skin type classification of I, II, or III (I always burns easily, never tans, II always burns easily, tans minimally, III Burns moderately, tans gradually)
• Body weight within 50.0 and 100.0 kg (inclusive), and body mass index (BMI) within the range 18.0 and 32.0 kg/m2 (inclusive)

Exclusion Criteria:

• A positive hepatitis B (HBsAg, anti-HBc), hepatitis C or HIV test at screening, indicative of a current or past infection
• A history of active tuberculosis (TB) or positive serological test for TB (Quantiferon TB Gold or T-SPOT)
• History of invasive opportunistic infections
• Participants with a history of Clostridium difficile-associated diarrhea
• Participants with a history of malignancy occurring within 5 years before inclusion (except adequately treated carcinoma in situ of the cervix, or adequately treated non-metastatic squamous cell or basal cell carcinoma of the skin)
• Active skin disorders or alterations such as tattoos on the back where photosensitivity testing will be performed or unprotected ultraviolet exposure of the test areas within 4 weeks prior to baseline photo testing that the Investigator considers will interfere with study assessments
• Abnormal skin response during preliminary or baseline phototoxicity evaluations
• Any medication within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication (whichever is longer); any acetaminophen intake within 2 days prior the inclusion and any biologics (antibody or its derivatives) given within 4 months before screening
• Any participant enrolled or having participated, in this or any other clinical study involving an IMP or in any other type of medical research within the past 14 days (last day of IMP dosing in the previous clinical trial) or 5 half-lives whichever is longer, before screening
• Clinical signs and symptoms consistent with COVID-19 or laboratory-confirmed SARS-CoV-2 infection; SARS-CoV-2 infection within 4 weeks prior to screening; and/or history of severe course of COVID-19
• If female, pregnancy (defined as positive beta-HCG blood test and/or positive urine pregnancy test), breast-feeding

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I SAR441566 Dose A; Participants will receive repeated low dose of SAR441566 for 7.5 days	Drug: SAR441566; Tablet
Experimental: Part I SAR441566 Dose B; Participants will receive repeated high dose of SAR441566 for 7.5 days	Drug: SAR441566; Tablet
Placebo Comparator: Part I Placebo; Participants will receive repeated SAR441566 matching placebo tablets for 7.5 days	Drug: Placebo; Tablet
Active Comparator: Part II Ciprofloxacin; Participants will receive repeated ciprofloxacin 500 mg twice-daily (BID) for 5.5 days	Drug: Ciprofloxacin; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment part I: Photosensitivity Index (PI) at 10 minutes post UV irradiation under Condition 1	The PI is calculated as the ratio of the minimal erythema dose (MEDbaseline) measured on Day -2 at 10 minutes post-irradiation to the corresponding MEDon-drug measured on Day 8 at 10 minutes post-irradiation. Condition 1 is Full range solar ultraviolet B/ultraviolet A (UVB/UVA) [290 to 400 nm] exposure.	On-drug Day 8
Treatment part I: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 1	The PI is calculated as the ratio of the minimal erythema dose (MEDbaseline) measured on Day -2 at 1 hour post-irradiation to the corresponding MEDon-drug measured on Day 8 at 1 hour post-irradiation. Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure.	On-drug Day 8
Treatment part I: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 1	The PI is calculated as the ratio of the minimal erythema dose (MEDbaseline) measured on Day -1 at 24 hours post-irradiation to the corresponding MEDon-drug measured on Day 9 at 24 hours post-irradiation. Condition 1 is a Full range solar UVB/UVA [290 to 400 nm] exposure.	On-drug Day 9
Treatment part I: Photosensitivity Index (PI) at 10 minutes post UV irradiation under Condition 2	The PI is calculated as the ratio of the minimal erythema dose (MEDbaseline) measured on Day -2 at 10 minutes post-irradiation to the corresponding MEDon-drug measured on Day 8 at 10 minutes post-irradiation. Condition 2 is a UVA only [320 to 400 nm] exposure.	On-drug Day 8
Treatment part I: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 2	The PI is calculated as the ratio of the minimal erythema dose (MEDbaseline) measured on Day -2 at 1 hour post-irradiation to the corresponding MEDon-drug measured on Day 8 at 1 hour post-irradiation. Condition 2 is a UVA only [320 to 400 nm] exposure.	On-drug Day 8
Treatment part I: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 2	The PI is calculated as the ratio of the minimal erythema dose (MEDbaseline) measured on Day -1 at 24 hours post-irradiation to the corresponding MEDon-drug measured on Day 9 at 24 hours post-irradiation. Condition 2 is a UVA only [320 to 400 nm] exposure.	On-drug Day 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment part I & part II: Minimum Erythema Dose (MED) percent change from baseline at 10 minutes, 1 hour, and 24 hours postirradiation measured under Condition 1 and Condition 2	Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure and condition 2 is a UVA only [320 to 400 nm] exposure.	Baseline (Day -2 to Day -1) and on-drug (Day 8 to Day 9)
Treatment part I & part II: Evaluation of local skin reactions following exposure to UV irradiation at 10 minutes, 1 hour, 24 hours, 48 hours, and 72 hours postirradiation under Condition 1, Condition 2, and Condition 3	Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure, condition 2 is a UVA only [320 to 400 nm] exposure and condition 3 is a full solar range UVB/UVA + UVA [16 J/cm2] exposure.	At Baseline (Day -2 to Day 1 pre-dose) and on-drug (Day 8 to Day 11)
Treatment part I: Assessment of Plasma pharmacokinetic parameter of SAR441566: Cmax	Maximum plasma concentration observed	Day 8 to Day 11
Treatment part I: Assessment of Plasma pharmacokinetic parameter of SAR441566: Tmax,	Time to reach Cmax	Day 8 to Day 11
Treatment part I: Assessment of Plasma pharmacokinetic parameter of SAR441566: AUC0-tau	Area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (0 to 24 hours)	Day 8 to Day 9
Treatment part I: Number of participants with adverse events (AE) and treatment-emergent adverse events (TEAEs)	Assessment of adverse events (AE) / treatment-emergent adverse events (TEAE) including serious adverse event (SAE) and adverse event of special interests (AESI)	Up to Day 20
Treatment part II: Photosensitivity Index (PI) at 10 minutes post UV irradiation under Condition 1	Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure.	On-drug Day 8
Treatment part II: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 1	Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure.	On-drug Day 8
Treatment part II: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 1	Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure.	On-drug Day 9
Treatment part II: Photosensitivity Index (PI) at 10 minutes Condition 2	Condition 2 is a UVA only [320 to 400 nm] exposure.	On-drug Day 8
Treatment part II: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 2	Condition 2 is a UVA only [320 to 400 nm] exposure.	On-drug Day 8
Treatment part II: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 2	Condition 2 is a UVA only [320 to 400 nm] exposure.	On-drug Day 9

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Actual): October 15, 2023
• Study Completion (Actual): October 23, 2023

Study Registration Dates

• First Submitted: April 12, 2023
• First Submitted That Met QC Criteria: April 25, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Ciprofloxacin
• Other Study ID Numbers: PDY16917; U1111-1255-5054 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No