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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Treatment part I: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 1
研究概览
简要总结
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.
详细描述
The overall duration of the study for each participant will be up to approximately 48 days
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Applicable for Part I
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
排除标准
- •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.
研究组 & 干预措施
Part I SAR441566 Dose A
Participants will receive repeated low dose of SAR441566 for 7.5 days
干预措施: SAR441566 (Drug)
Part I SAR441566 Dose B
Participants will receive repeated high dose of SAR441566 for 7.5 days
干预措施: SAR441566 (Drug)
Part I Placebo
Participants will receive repeated SAR441566 matching placebo tablets for 7.5 days
干预措施: Placebo (Drug)
Part II Ciprofloxacin
Participants will receive repeated ciprofloxacin 500 mg twice-daily (BID) for 5.5 days
干预措施: Ciprofloxacin (Drug)
结局指标
主要结局
Treatment part I: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 1
时间窗: 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 1 hour post UV irradiation under Condition 2
时间窗: 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 10 minutes post UV irradiation under Condition 1
时间窗: 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 24 hours post UV irradiation under Condition 1
时间窗: 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
时间窗: 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 24 hours post UV irradiation under Condition 2
时间窗: 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.
次要结局
- Treatment part I: Number of participants with adverse events (AE) and treatment-emergent adverse events (TEAEs)(Up to Day 20)
- Treatment part II: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 1(On-drug Day 8)
- 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))
- Treatment part II: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 1(On-drug 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(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(Day 8 to Day 11)
- Treatment part I: Assessment of Plasma pharmacokinetic parameter of SAR441566: Tmax,(Day 8 to Day 11)
- Treatment part I: Assessment of Plasma pharmacokinetic parameter of SAR441566: AUC0-tau(Day 8 to Day 9)
- Treatment part II: Photosensitivity Index (PI) at 10 minutes post UV irradiation under Condition 1(On-drug Day 8)
- Treatment part II: Photosensitivity Index (PI) at 10 minutes Condition 2(On-drug Day 8)
- Treatment part II: Photosensitivity Index (PI) at 1 hour post UV irradiation under Condition 2(On-drug Day 8)
- Treatment part II: Photosensitivity Index (PI) at 24 hours post UV irradiation under Condition 2(On-drug Day 9)