A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ATTO-1310 for the Treatment of Participants With Chronic Pruritus of Unknown Origin
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 300
- 主要终点
- ≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS) at Week 12 (WI-NRS4 response)
研究概览
简要总结
The goal of this clinical trial is to assess the efficacy and safety of ATTO-1310 in patients with chronic pruritus/itch of unknown origin.
The main questions it aims to answer are:
Does ATTO-1310 treatment alleviate symptoms of itch in participants with chronic pruritus/itch? What medical problems do participants have when taking ATTO-1310 for 24 weeks? Researchers will compare ATTO-1310 to a placebo (a look-alike substance that contains no drug). Participants will be dosed with ATTO-1310 or a placebo, visit the clinic for checkups and tests, and keep a diary of their symptoms.
详细描述
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of ATTO-1310 in adults with chronic pruritus/itch of unknown origin (CPUO). Participants with CPUO will receive one of three induction treatments (low dose ATTO-1310, high dose ATTO-1310, or placebo) for 12 weeks. Following induction, participants will be assessed for response to treatment. Response to the 12 week induction treatment will determine their treatment progression for the maintenance period. Responders will be re-randomized to one of 4 ATTO-1310 active treatment regimens (high or low dose combined with frequent or infrequent dosing). Non-responders and participants who received placebo during the induction period will be assigned to receive a high dose high frequency ATTO-1310 regimen for the maintenance period through 28 weeks. Participants will be followed for safety through week 36.
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
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 90 years with a body weight of 50 to 125 kg and body mass index (BMI) between 18.5 and 40 kg/m^
- •History of chronic pruritus for at least 6 months that is considered of unknown origin (without a clear association to another condition or medication) as assessed by the Investigator.
- •Chronic pruritus must affect at least 2 of the following body areas: legs, arms, or trunk.
- •History of inadequate control of pruritus with at least 1 antihistamine within 6 months of Screening.
- •Patient Global Impression of Severity (PGI-S) of pruritus of "severe" at Screening.
- •Use of a stable dose of topical bland emollient twice daily for at least 2 weeks immediately before Day 1
- •Weekly mean of daily WI-NRS ≥7 at Day 1
- •Negative pregnancy test
排除标准
- •Known condition, other than dry skin, that is considered by the Investigator to be the primary cause of chronic pruritus, including: Presence of a primary dermatologic condition associated with pruritic skin lesions, regional neuropathic pruritus with the exception of peripheral small fiber neuropathy, severe renal failure, hepatobiliary disease, recent infectious dermatoses, suspected somatoform pruritus, ongoing drug-induced pruritus, malignancy or hemopathy, uncontrolled endocrine disease,
- •Liver function tests (bilirubin, AST, ALT, alkaline phosphatase) >2.5 times above the upper limit of normal
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²
- •History of malignancy within 5 years of Screening
- •History of severe or uncontrolled asthma
- •History of known primary immunodeficiency, is considered immunocompromised, or has been treated for a parasitic infection in the past 6 months.
- •History of attempted suicide within the past 2 years.
- •History of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the IP excipients
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or is positive for HIV.
- •Active or untreated latent tuberculosis (TB) infection.
- •Any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before Day
- •History of drug or alcohol abuse within 1 year of Screening
研究组 & 干预措施
Placebo
Placebo induction
干预措施: Placebo (Drug)
ATTO-1310 Dose E
ATTO-1310 low dose high frequency maintenance
干预措施: ATTO-1310 (Drug)
ATTO-1310 Dose D
ATTO-1310 high dose low frequency maintenance
干预措施: ATTO-1310 (Drug)
ATTO-1310 Dose B
ATTO-1310 low dose induction
干预措施: ATTO-1310 (Drug)
ATTO-1310 dose F
ATTO-1310 low dose low frequency maintenance
干预措施: ATTO-1310 (Drug)
ATTO-1310 Dose A
ATTO-1310 high dose induction
干预措施: ATTO-1310 (Drug)
ATTO-1310 Dose C
ATTO-1310 high dose high frequency maintenance
干预措施: ATTO-1310 (Drug)
结局指标
主要结局
≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS) at Week 12 (WI-NRS4 response)
时间窗: Baseline and Week 12
Participants achieved a response if their WI-NRS improved 4 or more points from baseline on a scale ranging from zero (no itch) to 10 (worst possible itch). The baseline is calculated as the average in the final week prior to Day 1. The WI-NRS4 response endpoint at Week 12 is calculated as the average of the daily WI-NRS during Week 12 visit relative to the baseline average WI-NRS.
次要结局
- WI-NRS4 response at Week 4(Baseline and Week 4)
- ≥5-point improvement from baseline in WI-NRS (WI-NRS5 response) at Week 4(Baseline and Week 4)
- ≥5-point improvement from baseline in WI-NRS (WI-NRS5 response) at Week 12(Baseline and Week 12)
- WI-NRS <2 (WI-NRS<2 response) at Week 4(Week 4)
- WI-NRS <2 (WI-NRS<2 response) at Week 12(Week 12)
- Patient Global Impression of Severity (PGI-S) of pruritus of "none" or "mild" at Week 4(Week 4)
- Patient Global Impression of Severity (PGI-S) of pruritus of "none" or "mild" at Week 12(Week 12)
- Absolute change from baseline in weekly average WI-NRS at Week 4(Baseline, Week 4)
- Absolute change from baseline in weekly average WI-NRS at Week 12(Baseline, Week 12)
- Percent change from baseline in weekly average WI-NRS at Week 4(Baseline, Week 4)
- Percent change from baseline in weekly average WI-NRS at Week 12(Baseline, Week1 12)
- Absolute change from baseline in weekly average itch-related sleep disruption NRS (iSD-NRS) at Week 4(Baseline, Week 4)
- Absolute change from baseline in weekly average itch-related sleep disruption NRS (iSD-NRS) at Week 12(Baseline, Week 12)
- Percent change from baseline in weekly average iSD-NRS at Week 4(Baseline, Week 4)
- Percent change from baseline in weekly average iSD-NRS at Week 12(Baseline, Week 12)
- WI-NRS4 response through Week 28(Weekly through Week 28)
- Absolute change from baseline in weekly average WI-NRS through Week 28(Baseline and weekly through week 28)
- Percent change from baseline in weekly average WI-NRS through Week 28(Baseline and weekly through Week 28)
- Incidence and severity of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) from baseline through end of study (EOS)(Baseline through Day 253 (EOS))