A Phase I/II Proof of Concept, Open-Label, Repeat Dose, Dose Escalation Study of NM-002 in Adult Patients With Short Bowel Syndrome (SBS)
试验速览
- 阶段
- 1 期
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- To assess the safety and tolerability of repeated doses of NM002 three different dose levels
研究概览
简要总结
This is a Phase I/II. proof of concept, open label, two-dose, dose escalation study of NM-002 in adult patients with SBS who previously responded to exenatide. NM-002 is planned to be administered twice, at up to 3 different dose levels, in up to 3 cohorts, each consisting of 3-4 patients. Doses will be administered on Days 1 and 15 by subcutaneous injection. Patients will be monitored for their usage of parenteral supplementation, and will fill out a daily diary for their symptoms of SBS. Urine output will be measured on a daily basis. Patients will be followed for 6 weeks after the second dose.
详细描述
During a baseline period, all subjects will remain on their current prescription for administration of PS. Between Days -7 to -5 patients who have met initial screening criteria will return to the clinic and be enrolled into the study. Patients will be trained on diary usage and patients receiving the SBS meds will be instructed to discontinue use of their medications; Imodium, lomotil, and opium tincture.
On Day -4, subjects will begin diary entries. For 48 hours, on Days -1 and 0, patients will record in their diaries total urine output, PS usage, stool output and oral liquid intake.
On Study Day -1, patients will visit the clinic for baseline safety assessment, and review of symptoms of malabsorption and PS usage. Baseline SF36 and Bowel Symptom questionnaires will be administered.
On Day 1 of treatment, patients will return to the clinic with a sample of urine collected during the baseline run-in for urinalysis. They will have blood samples drawn for clinical laboratory assessment and for pre-dose PK levels, anti-drug antibody, and AE assessments. Following administration of study drug on Day 1, subjects will undergo additional serial PK blood draws.
Serial blood samples for the pharmacokinetic evaluation of NM-002 will be drawn on Days 1 and 15, with single samples obtained on 2, 3, 4, 5, 8, 16, 17, 18, 19, 22 and 29. Additional blood samples will be taken for clinical laboratory evaluations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Males and females with SBS secondary to surgical resection of small intestine, with or without an intact colon
- •18-75 years of age at the time of screening
- •Female subjects must be postmenopausal (at least 2 years prior to dosing) or surgically sterile or agree to use an acceptable form of birth control from screening until 30 days after last dose. If oral contraceptives are used, Subject must have been on a stable dose for ≥6 months. (See below, "Participation of Women", for additional detail.)
- •Male subjects must agree to use an acceptable form of birth control during the study and for 90 days after the last dose. Male subjects may not donate sperm for 90 days after last dose.
- •At least 6 months since last surgical bowel resection
- •Patients may be on Parenteral support (nutrition and/or fluid and electrolytes [PS]) for at least some of their nutritional needs.
- •If on PS, stable administration of PS volume for 1 month (±20% vol) prior to enrollment.
- •Able to ingest solid foods and drink
- •Willing to adhere to a defined oral intake of fluids on certain days as required by protocol and based on the individual's routine daily consumption.
排除标准
- •Positive results on the HIV, Hepatitis, or drug screens.
- •Pregnancy or lactation
- •Body mass index <18 or >30 kg/m2
- •Clinically significant intestinal adhesions and/or chronic abdominal pain
- •Active Crohn's disease or IBD (as evaluated by standard procedures employed by the investigator/institution). If in remission, must be ≥12 weeks of remission prior to enrollment.
- •If on chronic systemic narcotics, the patient must have been on a stable dose for >12 weeks
- •Inflammatory bowel disease patients who have NOT been on a stable drug treatment regimen for at least the past 3 months.
- •Visible blood in the stool within the last 3 months
- •Catheter sepsis experienced within the last 3 months
- •Known heart failure or active coronary disease
- •Known celiac disease
- •Radiation enteritis, scleroderma, coeliac disease, refractory or tropical sprue, diabetes
- •Alcohol or drug abuse within the last 12 months
- •Inadequate hepatic function as defined by: ALT and ASAST both >2.0X ULN; TBL >2X ULN; or ALP >2.5X ULN
- •Inadequate renal function as defined by serum creatinine <0.7 or >1.3 mg/dL (in men) and <0.6 or >1.1 mg/dL in women.
- •Personal or family history of medullary thyroid cancer.
- •History of pancreatitis.
- •Any patient who receives insulin in their PS.
- •Any hospitalization within 1 month before screening visit
- •Systemic corticosteroids, methotrexate, cyclosporine, tacrolimus, sirolimus, infliximab, or mycophenolate mofetil (CellCept®) within 30 days of screening
- •Any use of growth hormone, or growth factors such as native GLP-2 or GLP-2 analog (teduglutide) within the last 3 months
- •Use of antibiotics within the last 30 days
- •Subject not capable of understanding or not willing to adhere to the study visit schedules and other protocol requirements.
研究组 & 干预措施
Dose 1
NM-002 will be administered at the indicated dose by subcutaneous injection on Days 1 and 15.
干预措施: NM-002 (Drug)
Dose 2
NM-002 will be administered at the indicated dose by subcutaneous injection on Days 1 and 15.
干预措施: NM-002 (Drug)
Dose 3
NM-002 will be administered at the indicated dose by subcutaneous injection on Days 1 and 15.
干预措施: NM-002 (Drug)
结局指标
主要结局
To assess the safety and tolerability of repeated doses of NM002 three different dose levels
时间窗: 56 days
Assess adverse event profile of each dose and dose level
次要结局
未报告次要终点