The primary objective is to evaluate the efficacy of i) a prime-and-boost regimen with 20 µg Diamyd and ii) a prime-and-boost regimen with 20 µg Diamyd, followed by 2 additional single doses with 20 µg Diamyd, compared to placebo with respect…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change from baseline (Visit 2) to Month 15 (Visit 6) in C-peptide (AUCmean
0-120 min) during an MMTT.
Secondary outcome
• Hemoglobin A1c (HbA1c), change between baseline and subsequent visits
• Exogenous insulin dose per kg body weight and 24 hours, change between
baseline and subsequent
visits
• Number of self-reported episodes of hypoglycemia
• Fasting C-peptide, change between baseline and subsequent visits
• C-peptide AUCmean 0-120 min during MMTT, change between baseline and
subsequent visits
• C-peptide measured at 30, 60, 90, and 120 minutes during MMTT
• Maximum C-peptide during MMTT, change between baseline and subsequent visits
• Proportion of patients with a stimulated maximum C-peptide level above 0.2
nmol/L
+ safety variables as observation of reactions at the injection site, GAD65Ab
titer, occurrence of
adverse events (AEs), findings from: laboratory measurements, vital signs,
neurological assessments, and limited physical
examination.
Background summary
Type 1 diabetes (T1D) belongs to the group of medical disorders classified as
*autoimmune* due to a pathologic feature involving an inappropriate
immunological recognition of the body*s own tissues. This abnormal immune
response, in the case of T1D, results in the destruction of insulin-secreting
pancreatic beta cells which in turn leads to a lifelong dependence on exogenous
insulin treatment. Although the use of insulin has dramatically improved the
survival of patients with T1D, insulin does not represent a cure as individuals
with the disorder, even if well managed, display marked increases in the
frequency of life-altering (e.g., blindness, limb amputation) and even
life-threatening complications including hypoglycemic unawareness and
accelerated macrovascular disease. The severity of these complications makes
the development of a therapy allowing for beta cell preservation of great
urgency for patients and caregivers. The underlying basis of autoimmune
diabetes involves a *pro-inflammatory* T-cell response against
insulin-secreting beta cells that is sufficient to cause their destruction and
result in insufficient production of endogenous insulin. Diamyd therapy aims at
intervening in this destructive process by modulating the immune system in a
discrete, antigen-specific fashion to prevent the destruction of beta cells and
reduce or abolish dependence on insulin treatment.
Study objective
The primary objective is to evaluate the efficacy of i) a prime-and-boost
regimen with 20 µg Diamyd and ii) a prime-and-boost regimen with 20 µg Diamyd,
followed by 2 additional single doses with 20 µg Diamyd, compared to placebo
with respect to
preserving insulin secretion. This will be evaluated by the change from
baseline (Visit 2) to Month 15 (Visit 6) in C-peptide area under the curve mean
0-120 minutes (AUCmean 0- 120 min) during an MMTT.
Study design
This study is a 3-arm, randomized, double-blind, placebo-controlled,
multicenter, clinical trial. All groups will continue to receive intensive
diabetes management through their personal physician/diabetes team. Patients
will receive 2 subcutaneous injections with 20 µg Diamyd in a prime-and-boost
regimen, followed by 2 additional single doses with Diamyd 20µg, or 2
injections with 20 µg Diamyd in a prime-and-boost regimen, followed by 2
additional single doses with placebo, or placebo alone, depending on to which
treatment arm they are randomized.
Total duration of the study is 30 months (15 months blinded period with study
medication and 15 months follow-up)
Intervention
Each patient will receive four injections (Day 1, Day 30, Day 90 and Day 270)
Study burden and risks
Each patient receives 4 injections and has to remain in the study centre for
observation for at least 1 hour after each injection. At 6 visits a MMTT is
performed to measure the function of the beta cells. At each visit blood
samples are taken and for menarchal females a pregnancy test. The patient keeps
a diary during the study in which possible adverse events and hypoglycemia
periods are noted. Every day of the 4 days before a visit, the patient must
call the centre to report their daily use of insuline. At 7 visits the patient
should arrive fasting. At 8 visits a physical examination is carried out and at
5 visits a neurological exam.
The total study (two-and-a-half years) will mean 1-2 additional visit for the
patient in comparison with the visit frequency during standard diabetes care.
However the visits will last half an hour - two hours longer. Standard diabetes
care will be given during the study. No adverse events from the study
medication are expected. The burden for the patient during the visits has been
tried to keep as low as possible a.o. by using painkilling cream before the
needle stick and by using a catheter for blood sampling.
Linnégatan 89B, plan 5
SE-11523 Stockholm
Zweden
Linnégatan 89B, plan 5
SE-11523 Stockholm
Zweden
Listed location countries
Age
Inclusion criteria
1. Male and female patients between 10 and 20 years of age
2. Insulin dependent type 1 diabetes mellitus diagnosed within the previous
3 months at time of screening
3. Fasting C-peptide level at time of screening above 0.1 nmol/L
4. Elevated GAD65 antibodies (GADA) at time of screening
5. Menarchal females must agree to avoid pregnancy and have a negative urine
pregnancy test
6. Patients must agree to using adequate contraception, if sexually active, until 1
year after the last study drug administration
7. Must be willing to comply with intensive diabetes management
8. Written informed consent obtained from the patient and/or patient*s parents or
legal acceptable representative(s) according to local regulations.
Exclusion criteria
1. Previous or current treatment with immunosuppressant therapy (although
topical or inhaled steroids are accepted)
2. Treatment with any oral or injected anti-diabetic medications other than insulin
3. A history of anemia or significantly abnormal hematology results at screening
4. A history of epilepsy, head trauma or cerebrovascular accident, or clinical
features of continuous motor unit activity in proximal muscles
5. Clinically significant history of acute reaction to vaccines or other drugs in the
past
6. Treatment with any vaccine within 1 month prior to planned first Diamyd dose
or planned treatment with vaccine up to 2 months after the last injection with
Diamyd, excluding the influenza vaccine
7. Participation in other clinical trials with a new chemical entity within the
previous 3 months
8. Inability or unwillingness to comply with the provisions of this protocol
9. A history of alcohol or drug abuse
10. A significant illness other than diabetes within 2 weeks prior to first dosing
11. Known human immunodeficiency virus (HIV) or hepatitis
12. Females who are lactating or pregnant (for females who have started
menstruating the possibility of pregnancy must be excluded by urine βHCG onsite
within 24 hours prior to the investigational product administration)
13. Males or females not willing to use adequate contraception, if sexually active,
until 1 year after the last study drug administration
14. 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-002728-13-NL |
| CCMO | NL23850.003.08 |