A Phase 1a/b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of NTR-1011 in Healthy Adults and Adult Patients With Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 8
- 主要终点
- Safety and tolerability
研究概览
简要总结
The goal of this clinical trial is to inform the safety and tolerability of NTR-1011 in treating adult patients diagnosed with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It will also learn about the safety of NTR-1011 in healthy adult volunteers. The main questions it aims to answer are:
- What is the highest dose of NTR-1011 that is safe and well tolerated, when given under the skin or into a vein?
- How does the body process NTR-1011, and how does NTR-1011 affect the body?
- Does the body develop an immune response to NTR-1011?
- Are there early signs that NTR-1011 may benefit patients with SLE or RA when added to their current standard-of-care treatment?
In the first part of the study (Phase 1a, now complete), researchers compared single doses of NTR-1011 to a placebo (a look-alike substance that contains no drug) in 48 healthy volunteers to see how the body tolerates and processes the drug.
In the current part of the study (Phase 1b, actively recruiting), all participants receive NTR-1011 in addition to their usual SLE or RA treatment; there is no placebo group. Up to 24 participants with moderate-to-severe SLE or RA will:
- Receive five weekly doses of NTR-1011 given directly into a vein (intravenous)
- Continue their current standard-of-care treatment throughout the study
- Be monitored for 4 weeks after their last dose
- Be assigned to either the SLE group or the RA group (up to 12 patients each)
详细描述
This is a Phase 1a/1b, first-in-human study (LIBERATE-I) designed to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of NTR-1011 in healthy adults and in adult patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).
Mechanism of Action
NTR-1011 is a recombinant fusion protein combining human serum albumin (HSA) with DNASE1L3, an enzyme the body normally uses to break down neutrophil extracellular traps (NETs). NETs are web-like structures released by immune cells that help fight infection, but when they build up excessively or aren't cleared properly, they can contribute to tissue damage and inflammation in autoimmune diseases such as SLE and RA. NTR-1011 is designed to clear NETs systemically, with the goal of reducing this inflammatory process.
Phase 1a (completed, no longer enrolling)
The Phase 1a portion was a randomized, double-blind, placebo-controlled, single-ascending-dose study conducted in healthy adult volunteers, intended to establish an initial safety and tolerability profile and characterize single-dose PK and PD prior to dosing in patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Phase 1a - Healthy Volunteers (Completed, No Longer Enrolling)
- •Key Inclusion Criteria
- •Healthy men and women, 18-55 years of age
- •Body mass index (BMI) between 17.0 and 30.0 kg/m²
- •Good general health, confirmed by medical history, physical exam, vital signs, ECG, and lab testing
- •Willing and able to use highly effective contraception during and after the study
排除标准
- •Pregnant or breastfeeding
- •History of drug allergies or anaphylaxis to human, murine, or yeast proteins, monoclonal antibodies, or other allergens
- •Use of an investigational drug within 30 days (or 5 half-lives) before dosing
- •Positive test for hepatitis B, hepatitis C, or HIV
- •Clinically significant heart, lung, digestive, blood, autoimmune, psychiatric, or other medical condition
- •Clinically significant abnormal lab values (e.g., liver enzymes, blood counts) or ECG findings
- •Uncontrolled high blood pressure
- •Poor venous access
- •Phase 1b - Adult Patients with SLE and RA (Actively Recruiting)
- •General Inclusion Criteria (All Patients)
- •Men and women, 18-75 years of age
- •Able to understand and sign informed consent, and comply with study visits
- •Willing and able to use highly effective contraception during and after the study
- •Additional Inclusion Criteria - SLE Patients
- •Diagnosis of SLE for at least 6 months, meeting 2019 EULAR/ACR classification criteria
- •Active disease at screening
- •Positive lupus-related antibodies (e.g., anti-dsDNA, anti-Smith) and low complement (C3/C4)
- •On stable standard-of-care background therapy (e.g., antimalarials, low-dose corticosteroids, and at least one conventional DMARD)
- •Up to date on age-appropriate vaccinations Additional Inclusion Criteria - RA Patients
- •Diagnosis of RA for at least 3 months, meeting 2010 ACR/EULAR classification criteria
- •Moderate-to-severe active disease
- •Seropositive for rheumatoid factor and/or anti-CCP antibodies
- •On stable standard-of-care background therapy (e.g., low-dose corticosteroids and at least one conventional DMARD)
- •Key Exclusion Criteria (All Patients)
- •Pregnant or breastfeeding
- •Known allergy or reaction to NTR-1011, placebo components, or related products
- •Use of an investigational drug within 30 days (or 5 half-lives) before dosing, or concurrent enrollment in another clinical trial
- •History of cancer within the past year (with limited exceptions)
- •Significant kidney impairment, severe liver dysfunction, or severe lung disease
- •Uncontrolled high blood pressure or significant cardiovascular disease (e.g., recent heart attack or stroke, certain arrhythmias)
- •Active, recurrent, or high-risk infection, including active or latent tuberculosis without appropriate treatment, opportunistic infections, or chronic hepatitis B
- •Recent symptoms of COVID-19 without a documented negative test
- •Receipt of a live vaccine within 4 weeks before screening or planned within 4 weeks after last dose
- •Significant central nervous system disease or pain-amplification conditions (e.g., epilepsy, fibromyalgia) that could interfere with study assessments
- •Major surgery within 8 weeks before screening or planned within 6 months after baseline
- •History of bone marrow, stem cell, or solid organ transplant (except cornea)
- •Uncontrolled diabetes within the past 12 months (with some exceptions)
- •History of a blood clot within the past 12 months (with some exceptions)
- •Clinically significant abnormal lab values (e.g., liver enzymes, blood counts) at screening
研究组 & 干预措施
starting dose IV Patient
expected enzymatically and pharmacologically active IV dose in human SLE and RA patients
干预措施: NTR1011 (Drug)
结局指标
主要结局
Safety and tolerability
时间窗: 30 days
Incidence of safety and tolerability (DLTs) to inform RP2D
次要结局
未报告次要终点