A Phase 2 Study of QW Nimacimab Injection, Compared to Placebo Injection and QW Weekly Nimacimab Injection Co-administered With Semaglutide in Participants Who Are Overweight or Obese
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 136
- 试验地点
- 22
- 主要终点
- Percent change in body weight (main study)
研究概览
简要总结
This is a proof-of-concept study to assess the safety and efficacy of Nimacimab Injection compared to an active and placebo injection control.
详细描述
The purpose of this study is to measure the change in body weight with once weekly doses of Nimacimab Injection compared with placebo injection and once weekly Nimacimab Injection co-administered with commercially available semaglutide injection (Wegovy®) in participants with obesity or are overweight with weight-related comorbidities. A study extension has been added to include additional 26 weeks of treatment and 13 weeks of follow up for qualifying participants starting May2025.
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)
盲法说明
Participants assigned to combination arms will be masked to IP/placebo assignment but unmasked to Wegovy assignment. Participants in the monotherapy arms will remain masked to IP/placebo treatment assignment. Participants who enroll in the study extension (monotherapy arms) will be enrolled into an open-label unblinded 300 mg nimacimab treatment arm. Participants who enroll in the study extension (combination arms) will remain blinded to their treatment assignments with the exception of their Wegovy dose as in the main study.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- •Participants must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place to 65 years, inclusive, at the time of signing the informed consent.
- •Male, female, and/or nonbinary participants.
- •Have Body Mass Index (BMI) of
- •≥ 30 kg/m2 to ≤ 45 kg/m2 OR
- •≥ 27 kg/m2 and < 30 kg/m2 with clinically confirmed diagnosis of at least 1 of the following weight-related co-morbidities:
- •i. dyslipidemia: on lipid-lowering medication or having low-density lipoprotein (LDL) ≥ 160 mg/dL (4.1 mmol/L) or triglycerides ≥ 150 mg/dL (1.7 mmol/L) or high-density lipoprotein (HDL) < 40 mg/dL (1.0 mmol/L) for men or HDL < 50 mg/dL (1.3 mmol/L) for women at screening.
- •ii. cardiovascular disease: (for example, ischemic cardiovascular disease, New York Heart Association [NYHA] Functional Classification Class I-II heart failure).
- •iii. obstructive sleep apnea syndrome (Salzano 2021).
- •iv. controlled arterial hypertension with systolic blood pressure (SBP) < 150 mmHg or diastolic blood pressure (DBP) < 90 mmHg.
- •Have an HbA1c <6.5% at screening.
- •Have had a stable body weight for the 3 months prior to screening (no more than 5% body weight gain and/or loss).
- •If on cardiovascular, anti-hypertensive, must be controlled controlled on a stable dose for 3 months prior to randomization.
- •If on hormone replacement therapy, must be on a stable dose for at least 3 months prior to screening, including use of thyroxine.
- •Females of childbearing potential must agree:
- •to use an approved method of contraception from screening throughout the study and for at least 90 days after the last dose of study drug.
- •to not donate ova from screening throughout the study and for at least 90 days after the last dose of study drug.
- •have a negative pregnancy test at screening and Day
- •Male participants who are (hetero) sexually active must agree that he and his partner will each use an approved method of contraception from screening throughout the study and for at least 90 days after the last dose of study drug.
- •Agreement in male participants to not donate sperm from screening throughout the study and for at least 90 days after the last dose of study drug.
排除标准
- •Have any prior diagnosis of type 1 or type 2 diabetes mellitus (T1DM or T2DM, or rare forms of diabetes mellitus).
- •Have at least 1 laboratory value suggestive of diabetes during screening, including 1 or more of HbA1c ≥ 6.5% (48 mmol/mol), fasting serum glucose ≥ 126 mg/dL (7.0 mmol/L), or random glucose ≥ 200 mg/dL (11.1 mmol/L).
- •Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty, if performed > 1 year prior to screening).
- •Have obesity induced by other disorders (for example, Cushing's syndrome) or diagnosed monogenetic or syndromic forms of obesity (for example, Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome) or use of systemic corticosteroids or uncontrolled hypothyroidism. (Hypothyroidism on stable treatment is allowed if thyroid stimulating hormone (TSH) measure within the last 3 months of screening is within normal limits).
- •Have had at any time or plan to have endoscopic and/or device-based therapy for obesity including but not limited to the following:
- •Mucosal ablation,
- •Gastric artery embolization,
- •Intragastric balloon, OR
- •Duodenal-jejunal endoluminal liner
- •Surgery of any kind within 3 months prior to Day 0 (Baseline) with the exception of minor procedures or determined by the Investigator to be clinically relevant for participation in the study, or any planned surgery during the study.
- •Renal impairment as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, calculated at screening using the recommended method for estimating eGFR in adults from the National Kidney Foundation Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation (Charles 2024).
- •Acute kidney injury or dialysis within the last 3 months prior to the screening visit
- •Current malignancy with the exception of participants with basal cell carcinoma of this skin, suqamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
- •Positive results at screening that indicate an active virological infection at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus.
- •Previous organ or bone marrow transplant.
- •History and/or confirmed seizure disorder; reports febrile and/or idiopathic seizures occurring within the past 2 years.
- •Unstable cardiovascular disease as determined by the Investigator or medical history of myocardial infarction or arterial thromboembolic events within 3 months prior to screening or severe or unstable angina, NYHA Class III or IV disease, or a 12-lead ECG showing QTc interval (Fridericia's formula) >450 msec (males) or >470 msec (females), any tachyarrhythmia, pathologic Q waves, or any other abnormality deemed clinically significant in the opinion of the investigator.
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participants' participation for the full duration of the study, or is not in the best interest of the participants to participate in the opinion of the Investigator.
- •Have history of any of the following:
- •Major Depressive Disorder (MDD)
- •A lifetime history of suicide attempts
- •Other severe psychiatric disorder(s) (e.g., schizophrenia, bipolar disorder, etc.)
- •Use of anti-depressant medication
- •Have a Patient Health Questionnaire-9 (PHQ-9) score ≥ 10 at screening and/or Day 0 (Baseline).
- •At screening or Day 0 (Baseline) have any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) or any suicidal behavior in the lifetime or previous month.
- •History or presence of drug abuse (including medicinal and recreational marijuana use) within the 1 year prior to Day 0 (Baseline) or urine drug assay at screening or Day 0 (Baseline) positive (includes: amphetamines, barbiturates, cocaine metabolites, opiates, benzodiazepines, and cannabinoids).
- •Prior exposure to study drugs
- •Nimacimab injection
- •Glucagon-like peptide-1 (GLP-1) agonist.
- •Allergy to active or inactive component of Nimacimab
- •Allergy to active or inactive component(s) of GLP-1 agonist
- •Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study.
- •Aspartate aminotransferase (AST) or alanine transaminase (ALT) > 3 × upper limit of normal (ULN) at screening. One repeat test may be allowed within 7 days of the receiving the result, at the discretion of the Investigator.
- •Absolute neutrophil count ≤ 1.5 × 109/L.
- •Platelets ≤ 120 × 109/L.
- •Hemoglobin (Hgb) < 13.5 g/dL in males and < 12 g/dL in females.
- •Currently or have participated in a study of an investigational product or used an investigational device within 12 weeks and/or 5 times the half-life of the investigational product prior to the (Day 0, Baseline) first dose of study treatment.
- •Current use of any medication that is known to cause weight loss or participation in a structured weight loss program within the last 6 months prior to screening
- •Employees of the Sponsor, contract research organization (CO) involved in the conduct of the study, or investigational site, or immediate family members of the employees.
- •History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer of 1.5 ounces [45 mL] of hard liquor) within 6 months of screening.
- •Study Extension Eligibility Criteria
- •Participants are eligible to be included in the extension only if all the following criteria apply:
- •Completed Week 26 of the Main study including Week 25 on study treatment. Participants who completed Week 26 of the Main study but discontinued study treatment prior to that visit are not eligible to participate.
- •Participants in the combination arms (Nimacimab Injection or placebo + Semaglutide) of the Main study must roll over within 4 weeks of Main study Week 26
- •Participants in the monotherapy arms (Nimacimab Injection or placebo) of the Main study can roll over anytime after they have completed Week 26 on study treatment but before completing the 13-week follow-up period.
- •Does not have any condition that interferes with the ability to complete the Extension in the judgment of the investigator.
研究组 & 干预措施
Nimacimab injection
Nimacimab injection 200 mg
干预措施: Nimacimab injection (Biological)
Nimacimab placebo injection
Matching nimacimab placebo injection
干预措施: Nimacimab placebo injection (Biological)
Semaglutide injection + Nimacimab injection 200 mg
Semaglutide injection administered according to dose escalation described in semaglutide prescribing information plus concomitant administration of Nimacimab Injection 200 mg
干预措施: Nimacimab injection (Biological)
Semaglutide injection + Nimacimab injection 200 mg
Semaglutide injection administered according to dose escalation described in semaglutide prescribing information plus concomitant administration of Nimacimab Injection 200 mg
干预措施: semaglutide injection (Combination Product)
Semaglutide injection + Nimacimab placebo injection
Semaglutide injection administered according to dose escalation described in semaglutide Prescribing Information plus concomitant administration of Nimacimab Injection or matching placebo injection
干预措施: Nimacimab placebo injection (Biological)
Semaglutide injection + Nimacimab placebo injection
Semaglutide injection administered according to dose escalation described in semaglutide Prescribing Information plus concomitant administration of Nimacimab Injection or matching placebo injection
干预措施: semaglutide injection (Combination Product)
Open-label 300 mg Nimacimab injection (study extension)
Weekly nimacimab injection 300 mg open-label (study extension)
干预措施: Nimacimab 300 mg injection (Biological)
结局指标
主要结局
Percent change in body weight (main study)
时间窗: From Baseline to Week 26
Percent of participants who have a reduction in body weight
Nature, frequency and severity of AEs (study extension)
时间窗: Baseline through Week 38 of study extension (approximately 10 months of participation)
Nature, frequency and severity of treatment-emergent adverse events, including serious adverse events and adverse events of special interest
Part C - The nature, frequency, and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs)
时间窗: From baseline to end of follow up, approximately 4.5-5 months
Adverse events of special interest (AESI) include any psychiatric disorder-related AEs or neurological changes occurring after the first administration of study agent(s) in participants in this clinical study as determined by the Investigator. AESI include PHQ-9 score \> 10 that is increased from Baseline and/or C-SSRS changes (including any suicidal behavior or any suicidal ideation of type 4 or 5). Neurological changes evidenced by DSST or neurological examination occurring after the first administration of study agent(s) to participants in this study (See Section 8.6 and Section 8.7) may be considered AESIs as determined by the Investigator.
次要结局
- Change in body weight (main study)(From Baseline to Week 26)
- Change in waist circumference (main study)(From Baseline to Week 26)
- Change in waist circumference (study extension)(From baseline to Week 26 of study extension (approximately 7 months of participation))
- Change in lean versus fat mass ratio measured by DXA (study extension)(From baseline to Week 26 of study extension (approximately 7 months of participation))
- Change in lean versus fat mass ratio measured by DXA (main study)(From Baseline to Week 26)
- Change in BMI (main study)(From Baseline to Week 26)
- Part C - PK parameters for serum nimacimab(From baseline to end of follow up period, approximately 4.5-5 months)
- Change in BMI (study extension)(From baseline to Week 26 of study extension (approximately 7 months of participation))
- Percent of participants with greater than/equal to 5% body weight reduction as well as greater than/equal to 10% body weight reduction (main study)(From Baseline to Week 26)
- Percent change in body weight (kg) (study extension)(From baseline to Week 26 of study extension (approximately 7 months of participation))
- Part C - Titer of anti-nimacimab antibodies after repeated exposure to nimacimab monotherapy, and the titer of neutralizing antibodies(From baseline to end of follow up, approximately 4.5 - 5 months)