A Multicenter, Randomized, Comparative, Active-Controlled, Open label, Phase 3 Study to Evaluate the Efficacy and Safety of Semaglutide Injection in Comparison with Reference Biologic in Obesity Management.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 282
- 试验地点
- 23
- 主要终点
- Percentage change in body weight from baseline to week 24.
研究概览
简要总结
This is a A Multicenter, Randomized, Comparative, Active-Controlled, Open label, Phase 3 Study to Evaluate the Efficacy and Safety of Semaglutide Injection in Comparison with Reference Biologic in Obesity Management.
A total of 282 patients with obesity at geographically distributed centres in India will be enrolled in this clinical trial to evaluate the efficacy and safety of Semaglutide Injection compared to Reference Biologic Injection (Semaglutide). Patients with obesity having Body mass index (BMI) more than or equal to 30 kg/m2 or more than or equal to 27 kg/m2 with the presence of at least one of the weight-related comorbidities (treated or untreated) [i.e., hypertension, dyslipidaemia or type 2 diabetes mellitus (T2DM)] and history of at least one self-reported unsuccessful dietary effort to lose body weight will be considered for enrolment in this study along with reduced calorie diet and increased physical activity. The enrolled patients will be allocated to either of the 2 study groups according to the centralized computer-generated randomization plan in a 2:1 (test product : comparator product) ratio.
The patients with obesity as per pre-defined inclusion/exclusion criteria will be screened (visit 1) within 2 weeks prior to their enrolment. The eligible patients will then be enrolled and randomized to either of the 2 study groups as per their randomization number on baseline visit (visit 2, week 0, day 0). Subjects will be provided with patient diary (for all patients) and glucometer (for diabetic patients only) at randomization visit. After randomization, patients will then be followed up on an outpatient basis with scheduled visits at week 4 (visit 3), week 8 (visit 4), week 12 (visit 5), week 16 (visit 6), week 20 (visit 7) and week 24 (visit 8 – End of Treatment [EOT]). After 4 weeks of treatment, there will be a safety follow-up through telephonic visit at week 28 (visit 9 – End of Study [EOS]). This will be a parallel group study and all the enrolled patients will be instructed to take the study medications for a treatment period of 24 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female, aged 18 to 75 years (both inclusive) at the time of signing informed consent.
- •Patients with body mass index (BMI) greater than or equal to 30 kg/m2 or greater than or equal to 27 kg/m2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia or type 2 diabetes mellitus (T2DM).
- •Patients with a history of at least one self-reported unsuccessful dietary effort to lose body weight.
- •Patients willing to comply with the dietary and physical activity requirement during the study.
- •Patients and their female partners of childbearing potential should agree to use contraceptive measures throughout the study and for at least 2 months after end of treatment. (Note: Acceptable methods of contraception: A. Male: Vasectomy, Condoms, Total abstinence; B. Females: hormonal birth control e.g., combined estrogen and progestogen containing [oral, intravaginal, or transdermal] or progesterone only [oral, injectable, or implantable] hormonal contraception, intrauterine devices, intrauterine hormone releasing system, bilateral tubal occlusion, or total sexual abstinence).
- •Patient with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
- •Patients willing to comply with the protocol requirements. Inclusion Criteria Applicable for Type 2 Diabetes Mellitus Patients:
- •Patients with glycosylated haemoglobin (HbA1c) 7.0%.
- •10.0% (both inclusive) at screening visit.
- •Patients diagnosed with type 2 diabetes greater than or equal to 180 days prior to the day of screening.
- •Patients who are on a stable treatment with up to three oral glucose-lowering agents (Metformin, sulfonylureas, SGLT2 inhibitors, or Thiazolidinediones for at least 90 days before screening along with diet and exercise control.
排除标准
- •Patients with a history of type 1 diabetes mellitus.
- •Treatment with a GLP-1 receptor agonist (GLP-1 RA) within 180 days before screening.
- •Treatment with Semaglutide previously.
- •A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records.
- •Treatment with any medication for the indication of obesity within the past 90 days before screening.
- •Previous or planned (during the trial period) obesity treatment with surgery or a weight loss device.
- •However, the following are allowed: • Liposuction and/or abdominoplasty, if performed greater than 1 year before screening, • Lap banding, if the band has been removed greater than 1 year before screening, • Intragastric balloon if the balloon has been removed greater than 1 year before screening or • Duodenal-jejunal bypass sleeve if the sleeve has been removed greater than 1 year before screening.
- •Patients with uncontrolled thyroid disease, defined as thyroid stimulating hormone (TSH) greater than 6.0 mIU/L or less than 0.4 mIU/L.
- •Patients with a history of major depressive disorder within 2 years before screening.
- •Patients with a history of or diagnosis of other severe psychiatric disorder (e.g., schizophrenia, bipolar disorder etc.).
- •A lifetime history of a suicidal attempt.
- •Patients having Hamilton Depression Rating Scale (HAM-D; 17 items) total score greater than or equal to 10, and/or a score of greater than or equal to 2 on Suicide item of HAM-D 17-items scale at screening.
- •Patients with the use of any herbal/ non-herbal medicine with unknown/unspecified content within 90 days before screening.
- •Calcitonin greater than or equal to 50 ng/L at screening.
- •Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
- •Renal impairment measured as estimated glomerular filtration rate (eGFR) value of eGFR less than 30ml/min/1.73 m2 [Note: estimated glomerular filtration rate (eGFR) will be calculated using Modification of Diet in Renal Disease (MDRD) formula].
- •Patients with aspartate transaminase [AST] greater than 1.5 x upper limit of normal [ULN] OR alanine transaminase [ALT] greater than 1.5 x ULN OR alkaline phosphatase [ALP] greater than 1.5 x ULN OR total bilirubin greater than 1.5 x ULN) at screening.
- •Patients with a history of malignant neoplasms within the past 5 years prior to screening.
- •Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.
- •Patients with a history of myocardial infarction, stroke or hospitalization for unstable angina or transient ischaemic attack within the past 60 days prior to screening.
- •Patients with a presence of heart failure classified as being in New York Heart Association (NYHA) Class II, III and IV.
- •Surgery scheduled for the duration of the trial, except for minor surgical procedures, in the opinion of the investigator.
- •Patients with known or suspected abuse of alcohol or recreational drugs.
- •Patients with known or suspected hypersensitivity to trial product(s) or related products.
- •Patients with participation in another clinical trial within 90 days before screening.
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
- •Patients with any disorder, which in the investigator’s opinion, might jeopardise the subject’s safety or compliance with the protocol.
- •Exclusion Criteria for Non-Diabetic Patients:
- •Patients with glycosylated haemoglobin (HbA1c) greater than or equal yo 6.5% as measured at screening.
- •Treatment with glucose-lowering agent(s) within 90 days before screening.
- •Exclusion Criteria for Diabetic Patients:
- •Treatment with any medication for the indication of diabetes other than stated in the inclusion criteria (up to three oral glucose-lowering agents, i.e., Metformin, sulfonylureas, SGLT2 inhibitors, or Thiazolidinediones within the past 90 days prior day of screening.
结局指标
主要结局
Percentage change in body weight from baseline to week 24.
时间窗: Baseline and Week 24.
次要结局
- Adverse events & Serious adverse events (SAE) reported during the study.
- Percentage change in body weight from baseline to week 4, 8, 12, 16 and 20.(Baseline, Week 4, Week 8, Week 12, Week 16 and Week 20.)
- Proportion of patients having body weight reduction more than or equal to 5% from baseline at week 4, 8 12, 16, 20 and 24.(Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24.)
- Proportion of patients having body weight reduction more than or equal to 10 % from baseline at week 4, 8, 12, 16, 20 and 24.(Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24.)
- Change in BMI from baseline to week 4, 8, 12, 16, 20 and 24.(Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24.)
- Change in waist circumference from baseline to week 4, 8, 12, 16, 20 and 24.(Baseline, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24.)
- Change in Physical functioning score (SF) 36 total score from baseline to week 4, 8, 12, 16 and 24.(Baseline, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24.)
- For Diabetic Patients(Change in glycosylated hemoglobin from baseline to week 12 and 24.)
- For Diabetic Patients(Change in FPG & PPG from baseline to week 4, 8, 12, 16, 20 and 24.)
- For Non-diabetic patients(Change in glycosylated hemoglobin, FPG & PPG from baseline to week 24.)
- Number of patients discontinued due to AEs during course of trial.(Throughout the study.)
- Number of patients requiring hypoglycaemia management (for diabetic patients only).(Throughout the study.)
- Proportion of patients with anti-drug antibodies (ADA) and Neutralizing Antibody (Nab) at week 24 compared to pre-dose (enrolment, Day 0 - visit 2).(Day 0 and Week 24.)
研究者
Dr Deven V Parmar
Zydus Lifesciences Limited