Master Protocol of Three Randomized, Double-blind, Placebo Controlled, Multi-center, Parallel-group Studies of Dupilumab in Patients With Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite the Use of H1 Antihistamine Treatment in Patients naïve to Omalizumab and in Patients Who Are Intolerant or Incomplete Responders to Omalizumab
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 397
- 试验地点
- 98
- 主要终点
- Change From Baseline in Weekly Itch Severity Score at Week 24
研究概览
简要总结
Primary Objective:
This study aimed to demonstrate the efficacy of dupilumab in study participants with CSU who remained symptomatic despite the use of H1 antihistamine (Study A and C: omalizumab naïve; Study B: omalizumab intolerant or incomplete responders)
Secondary Objectives:
This study aimed to demonstrate the efficacy of dupilumab on urticaria activity composite endpoint and itch or hives, separately, at various timepoints This study aimed to demonstrate the efficacy of dupilumab on angioedema This study aimed to demonstrate the efficacy of dupilumab on urticaria control This study aimed to demonstrate improvement in health-related quality of life and overall disease status and severity This study aimed to evaluate the ability of dupilumab in reducing the proportion of participants who require treatment with oral corticosteroids (OCS) This study aimed to evaluate safety outcome measures This study aimed to evaluate immunogenicity of dupilumab
详细描述
The duration of study for each participant included 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study A and C: Participant were ≥6 years to 80 years of age at the time of signing the informed consent.
- •Study B: Participant were ≥12 years (or the minimum legal age for adolescents in the country of the investigational site) to 80 years of age at the time of signing the informed consent
- •Participants who had a diagnosis of CSU refractory to H1 antihistamines (H1-AH) at the time of randomization defined by
- •Diagnosis of CSU>6 months prior to screening visit
- •Presence of itch and hives for >6 consecutive weeks at any time prior to screening visit despite the use of H1-AH during that time period
- •Used a study defined H1-antihistamine for CSU treatment
- •During the 7 days before randomization:
- •UAS7≥16 ISS7≥ 8
- •Study A and C: omalizumab naïve, Study B; intolerant or incomplete responder to omalizumab
- •Participants were willing and able to complete a daily symptom e-Diary for the duration of the study
排除标准
- •Participants were excluded from any of the studies if any of the following criteria apply:
- •Weight was less than 30 kg in adults and adolescents and 15 kg in children aged 6 to<12years
- •Clearly defined underlying etiology for chronic urticarias other than CSU
- •Presented of skin morbidities other than CSU that may interfere with the assessment of the study outcomes
- •Active atopic dermatitis
- •Severe concomitant illness(es) that, in the investigator's judgment, would have adversely affected the participant's participation in the study
- •Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
- •Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection
- •Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit and during the screening period
- •Known or suspected immunodeficiency
- •Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin
- •History of systemic hypersensitivity or anaphylaxis to omalizumab or any biologic therapy, including any excipients
- •Participation in prior dupilumab clinical study, or have been treated with commercially available dupilumab.
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Study A Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study A Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: Dupilumab SAR231893 (Drug)
Study A Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study A Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: Placebo (Drug)
Study B Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: Dupilumab SAR231893 (Drug)
Study B Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study B Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: Placebo (Drug)
Study B Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study C Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: Dupilumab SAR231893 (Drug)
Study C Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study C Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: Placebo (Drug)
Study C Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study A Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: Dupilumab SAR231893 (Drug)
Study A Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study A Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: Placebo (Drug)
Study A Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study B Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: Dupilumab SAR231893 (Drug)
Study B Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study B Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: Placebo (Drug)
Study B Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study C Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: Dupilumab SAR231893 (Drug)
Study C Dupilumab
dose regimens, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study C Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: Placebo (Drug)
Study C Matched Placebo
placebo, on top of non-sedating H1-antihistamine
干预措施: non sedating H1-antihistamine (Drug)
Study A Dupilumab
Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
- 300 milligrams (mg) SC injection every 2 weeks (q2w) for adults and those adolescents who weighed >=60 kilograms (kg) at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
- 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
- 300 mg SC injection every 4 weeks (q4w) for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.
干预措施: Dupilumab SAR231893 (Drug)
Study A Dupilumab
Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
- 300 milligrams (mg) SC injection every 2 weeks (q2w) for adults and those adolescents who weighed >=60 kilograms (kg) at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
- 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
- 300 mg SC injection every 4 weeks (q4w) for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.
干预措施: non sedating H1-antihistamine (Drug)
Study A Placebo
Participants who were omalizumab naïve received placebo matched to dupilumab as subcutaneous (SC) injection including loading dose from Day 1 up to 24 weeks.
干预措施: Placebo (Drug)
Study A Placebo
Participants who were omalizumab naïve received placebo matched to dupilumab as subcutaneous (SC) injection including loading dose from Day 1 up to 24 weeks.
干预措施: non sedating H1-antihistamine (Drug)
Study B Dupilumab
Participants who were intolerant or incomplete responders to omalizumab received dupilumab for 24 weeks as follows:
- 300 mg SC injection q2w for adults and those adolescents weighing >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1 or
- 200 mg SC injection q2w for adolescents weighing <60 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1.
干预措施: Dupilumab SAR231893 (Drug)
Study B Dupilumab
Participants who were intolerant or incomplete responders to omalizumab received dupilumab for 24 weeks as follows:
- 300 mg SC injection q2w for adults and those adolescents weighing >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1 or
- 200 mg SC injection q2w for adolescents weighing <60 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1.
干预措施: non sedating H1-antihistamine (Drug)
Study B Placebo
Participants who were intolerant or incomplete responders to omalizumab received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.
干预措施: Placebo (Drug)
Study B Placebo
Participants who were intolerant or incomplete responders to omalizumab received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.
干预措施: non sedating H1-antihistamine (Drug)
Study C Dupilumab
Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
- 300 mg SC injection q2w for adults and those adolescents who weighed >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
- 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
- 300 mg SC injection q4w for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.
干预措施: Dupilumab SAR231893 (Drug)
Study C Dupilumab
Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
- 300 mg SC injection q2w for adults and those adolescents who weighed >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
- 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
- 300 mg SC injection q4w for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.
干预措施: non sedating H1-antihistamine (Drug)
Study C Placebo
Participants who were omalizumab naïve received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.
干预措施: Placebo (Drug)
Study C Placebo
Participants who were omalizumab naïve received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.
干预措施: non sedating H1-antihistamine (Drug)
Study C Placebo
Participants who were omalizumab naïve received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.
干预措施: Placebo (Drug)
Study A Dupilumab
Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
- 300 milligrams (mg) SC injection every 2 weeks (q2w) for adults and those adolescents who weighed >=60 kilograms (kg) at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
- 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
- 300 mg SC injection every 4 weeks (q4w) for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.
干预措施: Dupilumab SAR231893 (Drug)
Study A Dupilumab
Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
- 300 milligrams (mg) SC injection every 2 weeks (q2w) for adults and those adolescents who weighed >=60 kilograms (kg) at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
- 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
- 300 mg SC injection every 4 weeks (q4w) for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.
干预措施: non sedating H1-antihistamine (Drug)
Study A Placebo
Participants who were omalizumab naïve received placebo matched to dupilumab as subcutaneous (SC) injection including loading dose from Day 1 up to 24 weeks.
干预措施: Placebo (Drug)
Study A Placebo
Participants who were omalizumab naïve received placebo matched to dupilumab as subcutaneous (SC) injection including loading dose from Day 1 up to 24 weeks.
干预措施: non sedating H1-antihistamine (Drug)
Study B Dupilumab
Participants who were intolerant or incomplete responders to omalizumab received dupilumab for 24 weeks as follows:
- 300 mg SC injection q2w for adults and those adolescents weighing >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1 or
- 200 mg SC injection q2w for adolescents weighing <60 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1.
干预措施: Dupilumab SAR231893 (Drug)
Study B Dupilumab
Participants who were intolerant or incomplete responders to omalizumab received dupilumab for 24 weeks as follows:
- 300 mg SC injection q2w for adults and those adolescents weighing >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1 or
- 200 mg SC injection q2w for adolescents weighing <60 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1.
干预措施: non sedating H1-antihistamine (Drug)
Study B Placebo
Participants who were intolerant or incomplete responders to omalizumab received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.
干预措施: Placebo (Drug)
Study B Placebo
Participants who were intolerant or incomplete responders to omalizumab received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.
干预措施: non sedating H1-antihistamine (Drug)
Study C Dupilumab
Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
- 300 mg SC injection q2w for adults and those adolescents who weighed >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
- 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
- 300 mg SC injection q4w for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.
干预措施: Dupilumab SAR231893 (Drug)
Study C Dupilumab
Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
- 300 mg SC injection q2w for adults and those adolescents who weighed >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
- 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
- 300 mg SC injection q4w for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.
干预措施: non sedating H1-antihistamine (Drug)
Study C Placebo
Participants who were omalizumab naïve received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.
干预措施: non sedating H1-antihistamine (Drug)
结局指标
主要结局
Change From Baseline in Weekly Itch Severity Score at Week 24
时间窗: Baseline (Day 1) and Week 24
ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. Least squares (LS) mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.
次要结局
- Change From Baseline in Weekly Urticaria Activity Score at Week 24(Baseline (Day 1) and Week 24)
- Change From Baseline in Weekly Hives Severity Score at Week 24(Baseline (Day 1) and Week 24)
- Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24(Week 24)
- Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24(Week 24)
- Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24(Week 24)
- Change From Baseline in Urticaria Control Test (UCT) at Week 24(Baseline (Day 1) and Week 24)
- Change From Baseline in Weekly Itch Severity Score at Week 12(Baseline (Day 1) and Week 12)
- Change From Baseline in Weekly Urticaria Activity Score at Week 12(Baseline (Day 1) and Week 12)
- Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12(Week 12)
- Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12(Week 12)
- Change From Baseline in Weekly Hives Severity Score at Week 12(Baseline (Day 1) and Week 12)
- Change From Baseline in Urticaria Control Test at Week 12(Baseline (Day 1) and Week 12)
- Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20(Baseline (Day 1) and Weeks 4, 8, 16 and 20)
- Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period(Baseline (Day 1) up to Week 24)
- Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24(Baseline (Day 1) and Weeks 12 and 24)
- Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24(Baseline (Day 1) and Weeks 12 and 24)
- Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24(Weeks 12 and 24)
- Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24(Baseline (Day 1) and Weeks 12 and 24)
- Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24(Baseline (Day 1) and Weeks 12 and 24)
- Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24(Weeks 12 and 24)
- Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period(Baseline (Day 1) up to Week 24)
- Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period(Baseline (Day 1) up to Week 24)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From first dose of study intervention (Day 1) up to end of follow-up, approximately 36 weeks each for Study A, B and C)
- Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab(Up to Week 24)