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

Sponsor

Sanofi (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05844735

Collaborator

(none)

Enrollment

Arms

4.3

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: SAR441566 Drug: Placebo Drug: Ciprofloxacin	Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Applicable for Part I

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 18, 2023

Anticipated Primary Completion Date :

Sep 17, 2023

Anticipated Study Completion Date :

Sep 27, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Treatment part I: Photosensitivity Index (PI) at 10 minutes post UV irradiation under Condition 1 [On-drug Day 8]
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.
Treatment part I: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 1 [On-drug Day 8]
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.
Treatment part I: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 1 [On-drug Day 9]
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.
Treatment part I: Photosensitivity Index (PI) at 10 minutes post UV irradiation under Condition 2 [On-drug Day 8]
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.
Treatment part I: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 2 [On-drug Day 8]
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.
Treatment part I: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 2 [On-drug Day 9]
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.

Secondary Outcome Measures

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 [Baseline (Day -2 to Day -1) and on-drug (Day 8 to Day 9)]
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.
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 [At Baseline (Day -2 to Day 1 pre-dose) and on-drug (Day 8 to Day 11)]
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.
Treatment part I: Assessment of Plasma pharmacokinetic parameter of SAR441566: Cmax [Day 8 to Day 11]
Maximum plasma concentration observed
Treatment part I: Assessment of Plasma pharmacokinetic parameter of SAR441566: Tmax, [Day 8 to Day 11]
Time to reach Cmax
Treatment part I: Assessment of Plasma pharmacokinetic parameter of SAR441566: AUC0-tau [Day 8 to Day 9]
Area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (0 to 24 hours)
Treatment part I: Number of participants with adverse events (AE) and treatment-emergent adverse events (TEAEs) [Up to Day 20]
Assessment of adverse events (AE) / treatment-emergent adverse events (TEAE) including serious adverse event (SAE) and adverse event of special interests (AESI)
Treatment part II: Photosensitivity Index (PI) at 10 minutes post UV irradiation under Condition 1 [On-drug Day 8]
Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure.
Treatment part II: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 1 [On-drug Day 8]
Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure.
Treatment part II: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 1 [On-drug Day 9]
Condition 1 is full range solar UVB/UVA [290 to 400 nm] exposure.
Treatment part II: Photosensitivity Index (PI) at 10 minutes Condition 2 [On-drug Day 8]
Condition 2 is a UVA only [320 to 400 nm] exposure.
Treatment part II: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 2 [On-drug Day 8]
Condition 2 is a UVA only [320 to 400 nm] exposure.
Treatment part II: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 2 [On-drug Day 9]
Condition 2 is a UVA only [320 to 400 nm] exposure.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG.
Participants who are men or women of non childbearing potential
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); 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 The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Sanofi

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT05844735

Other Study ID Numbers:

PDY16917
U1111-1255-5054

First Posted:

May 6, 2023

Last Update Posted:

May 6, 2023

Last Verified:

Apr 7, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Ciprofloxacin

Study Results

No Results Posted as of May 6, 2023