Open Label Pilot Trial in Adults With Recent-onset T1D to Evaluate the Safety, Diabetes Status and Immune Response of GAD-antigen (Diamyd®) Therapy Administered Into Lymph Nodes in Combination With an Oral Vitamin D Regimen
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of Subjects With Injection Site Reactions Month 32
研究概览
简要总结
The objectives of the main study is to:
- Evaluate the safety of giving GAD-Alum (Glutamic acid decarboxylase) (Diamyd) directly into lymph glands in combination with an oral vitamin D regimen
- Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion.
The objective of the sub-study is to:
- Evaluate safety after a fourth injection with 4 μg GAD-Alum direct into an inguinal lymph gland in 3 adult patients from the main study
- Evaluate how the above mentioned treatment influences the immune system and endogenous insulin secretion.
详细描述
Eligible patients will be treated with 4 µg GAD-Alum into an inguinal lymph gland at three occasions, with one month intervals in combination with Vitamin D (14 000 IU/week) for 4 months, starting 1 month prior to first GAD-Alum injection.
A sub-study will include three adult patients from the main study and evaluate safety after a fourth injection with 4 μg GAD-Alum into an inguinal lymph gland in combination with oral vitamin D intake. The Prolonged Extension Study Period is 12 months and will start 30,5 months after baseline.
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
入排标准
- 年龄范围
- 12 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent given by patients
- •Type 1 diabetes according to the ADA (American Diabetes Association) classification with < 6 months diabetes duration
- •Age 12.00-29.99 years at diagnosis of Type 1 diabetes
- •Fasting C-peptide ≥0.12 nmol/L
- •Pos GADA(Antibodies to GAD with molecular mass 65,000) but < 50 000 random units
- •Females must agree to avoid pregnancy and have a negative urine pregnancy test
- •Patients of childbearing potential must agree to using adequate contraception, until 1 year after the last administration of GAD-Alum.
排除标准
- •Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
- •Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
- •Treatment with any oral or injected anti-diabetic medications other than insulin
- •Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
- •A history of anaemia or significantly abnormal haematology results at screening
- •A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles
- •Clinically significant history of acute reaction to vaccines or other drugs in the past
- •Treatment with any vaccine, including influenza vaccine, within 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months after the last injection with study drug.
- •Participation in other clinical trials with a new chemical entity within the previous 3 months
- •Inability or unwillingness to comply with the provisions of this protocol
- •A history of alcohol or drug abuse
- •A significant illness other than diabetes within 2 weeks prior to first dosing
- •Known human immunodeficiency virus (HIV) or hepatitis
- •Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG (beta-human chorionic gonadotropin) on-site within 24 hours prior to the GAD-Alum treatment)
- •Males or females not willing to use adequate contraception until 1 year after the last GAD-Alum treatment
- •Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study
- •Deemed by the investigator not being able to follow instructions and/or follow the study protocol
研究组 & 干预措施
GAD-Alum+Vitamin D
GAD-Alum (Diamyd) injected into Lymph Nodes Dosage and interval: One injection of 4 µg Diamyd will be administered into the lymph nodes at three occasions, with one month intervals
Vitamin D (Calciferol) in oral solution. Dosage and interval: 2000 IU daily for 120 days
干预措施: GAD-Alum (Drug)
GAD-Alum+Vitamin D
GAD-Alum (Diamyd) injected into Lymph Nodes Dosage and interval: One injection of 4 µg Diamyd will be administered into the lymph nodes at three occasions, with one month intervals
Vitamin D (Calciferol) in oral solution. Dosage and interval: 2000 IU daily for 120 days
干预措施: Vitamin D (Drug)
结局指标
主要结局
Number of Subjects With Injection Site Reactions Month 32
时间窗: Month 32, extension period
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 1
时间窗: Month 1
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 3
时间窗: Month 3
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 2
时间窗: Month 2
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
次要结局
- Mean Change in C-peptide AUC(Mean 120min) Value, Month 30(Baseline to month 30 at 0, 30, 60, 90, 120 minutes post-dose)
- Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15(Baseline to month 15 at 0, 30, 60, 90, 120 minutes post-dose)
- Mean Change in C-peptide AUC(Mean 120min) Value, Month 43(Baseline to month 43, extension period at 0, 30, 60, 90, 120 minutes post-dose)
- Mean Change in C-peptide 90-minute Value, Month 30(Baseline to month 30)
- Mean Change in C-peptide 90-minute Value, Month 43(Baseline to month 43, extension period)
- Mean Change in Fasting C-peptide Value, Month 15(Baseline to month 15)
- External Insulin Dose, Month 30(Month 30)
- External Insulin Dose, Month 43(Month 43, extension period)
- Mean IDAA1c Values, Baseline(Baseline)
- Mean IDAA1c Values, Month 30(Month 30)
- Mean IDAA1c Values, Month 43(Month 43, extension period)
- Mean Change in Fasting C-peptide Value, Month 30(Baseline to month 30)
- Mean Change in Fasting C-peptide Value, Month 43(Baseline to month 43, extension period)
- Mean Change in HbA1c, Month 15(Baseline to month 15)
- Mean Change in HbA1c, Month 30(Baseline to month 30)
- Mean Change in C-peptide 90-minute Value, Month 15(Baseline to month 15)
- Mean Change in HbA1c, Month 43(Baseline to month 43, extension period)
- Mean IDAA1c Values, Month 15(Month 15)
- External Insulin Dose, Baseline(Baseline)
- External Insulin Dose, Month 15(Month 15)
研究者
Johnny Ludvigsson
MD, PhD, Professor
Linkoeping University