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

Study Overview
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Brief Summary
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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.

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

Official Title
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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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: SAR441566
* Drug: Placebo
* Drug: Ciprofloxacin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |