A Randomized, Double-blind, Placebo Controlled, Dose-finding Study to Assess the Efficacy and Safety of SAR443122 in Adult Patients With Moderate to Severe Ulcerative Colitis
概览
- 阶段
- 2 期
- 干预措施
- Placebo
- 疾病 / 适应症
- Colitis Ulcerative
- 发起方
- Sanofi
- 入组人数
- 187
- 试验地点
- 168
- 主要终点
- Proportion of participants who achieve clinical remission at Week 12 by modified Mayo Score (mMS)
- 状态
- 进行中（未招募）
- 最后更新
- 5天前
概览
简要总结
This is a randomized, double-blind, placebo controlled, dose-ranging Phase 2 study. The primary objective is to evaluate the efficacy and safety of SAR443122 compared to placebo in participants with moderate to severe UC. Dose selection for further clinical development will be based on the multiple efficacy, safety and PK parameters.
The study consists of 4 parallel arms (3 dose groups of SAR443122 vs placebo) to assess the efficacy and safety of SAR443122 in participants with moderate to severe UC. All participants will receive a total of 52 weeks (a 12-week induction treatment phase and a 40-week maintenance phase) of study treatment, except if treatment should be discontinued per investigator's assessment.
At the end of the first 12 weeks of induction treatment, all participants in clinical response or remission will be offered study treatment up to 40 weeks and will continue with the same blinded treatment that was assigned. Participants who do not achieve clinical response or remission at the end of the initial 12 weeks induction treatment will roll over in an open-label treatment arm and will be treated with SAR443122 at the highest tested dose.
In addition, participants from the maintenance treatment that lose clinical efficacy at any time up to V10/Week 40 (Week 28 of maintenance) will be offered to roll over in the open-label treatment arm with SAR443122 at the highest dose.
详细描述
Total study duration per participant will be up to 58 weeks, including a screening period of up to 4 weeks, a treatment period up to 52 weeks and a post-treatment follow-up period of 2 weeks.
研究者
入排标准
入选标准
- •Participants who have clinical evidence of active Ulcerative Colitis \[UC\] for ≥3 months before screening as confirmed by endoscopy during the screening period.
- •Participants must have a minimum disease extent of 15 centimeters from the anal verge.
- •Participants are inadequate or non-responders, have shown loss of response, or are intolerant to at least 1 of following approved treatments: amino-salicylate, corticosteroids, immunosuppressants or biologics other than natalizumab (Tysabri®) or small molecules.
- •Participants on corticosteroids must be on a stable dose ≥2 weeks prior to screening and during screening period.
- •Participants on methotrexate, azathioprine or 6- mercaptopurine must be on treatment for at least 8 weeks prior to screening; and on a stable dose ≥4 weeks prior to screening and during screening period.
- •Participants on oral 5-aminosalicylates, mesalamine or sulfasalazine must be on a stable dose for ≥4 weeks prior to screening and during screening period.
- •Participants on advanced therapies must have 1) last administration at least 5 half-lives prior to randomization, or 2) undetectable level of the biologic in their blood prior to randomization.
- •Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women participants should not be pregnant or breastfeeding.
排除标准
- •Participants with Crohn's Disease (CD).
- •Participants with diagnosis of indeterminate colitis or microscopic colitis.
- •Participants with stool sample positive for culture for aerobic pathogens or C difficile.
- •Participants with prior colectomy or anticipated colectomy during their participation in the study.
- •Participants with presence of ileal pouch or ostomy.
- •Participants with fulminant disease or toxic megacolon.
- •Participants with colonic dysplasia except for adenoma.
- •Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition (TPN).
- •Participants with history of recurrent or recent serious infection that has not resolved within 4 weeks prior to randomization.
- •Participants presenting with active malignancies or recurrence of malignancy within the 5 years before screening.
研究组 & 干预措施
Placebo
Matching Placebo
干预措施: Placebo
SAR443122 level 1
Dose level 1
干预措施: SAR443122
SAR443122 level 2
Dose level 2
干预措施: SAR443122
SAR443122 level 3
Dose level 3
干预措施: SAR443122
结局指标
主要结局
Proportion of participants who achieve clinical remission at Week 12 by modified Mayo Score (mMS)
时间窗: At Week 12
The Mayo score (full MS) is a composite instrument that consists of patient reported stool frequency and rectal bleeding, endoscopy-derived measures and physician-reported assessment (PGA). The modified Mayo score is calculated omitting PGA. And an endoscopy score of 1 with no friability.
次要结局
- Proportion of participants who achieve endoscopic improvement at Week 12(At Week 12)
- Proportion of participants who achieve clinical response at Week 12 by mMS(At Week 12)
- Change from baseline in bowel signs and symptoms assessed by Ulcerative Colitis Patient Reported Outcome Signs and Symptoms (UC-PRO/SS) at Week 12(At Week 12)
- Proportion of participants who achieve clinical remission at Week 12 by full Mayo Score (MS)(At Week 12)
- Change from baseline in abdominal signs and symptoms assessed by UC-PRO/SS at Week 12(At Week 12)
- Pharmacokinetic parameters: maximum concentration [Cmax](Until Week 52)
- Pharmacokinetic parameters: elimination half-life [t1/2z](Until Week 52)
- Pharmacokinetic parameters: time to Cmax [tmax](Until Week 52)
- Pharmacokinetic parameters: area under the curve over the dosing interval [AUC0-tau](Until Week 52)
- Participants with any Treatment Emergent Adverse Events (TEAEs) during induction and maintenance treatment period(Until Week 52)
- Participants with any TEAEs during open-label treatment period(Up to Week 52)
- Proportion of participants who achieve clinical response at Week 12 by MS.(At Week 12)
- Change from baseline on patient-reported outcome 2 (PRO2) total score (Mayo stool frequency and rectal bleeding subscores) over time(From baseline to Week 12)
- Proportion of participants who achieve Histologic-endoscopic mucosal improvement (HEMI) at Week 12 defined by achievement of modified Mayo endoscopic improvement and histological improvement(At Week 12)
- Proportion of participants who achieve histological improvement at Week 12(At Week 12)
- Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12(At Week 12)