Injections of Glutamic Acid Decarboxylase (GAD) for LADA Type of Diabetes

Phase 2

Completed

• Conditions: Latent Autoimmune Diabetes in Adults
• Interventions: Drug: recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel; Drug: Vitamin D

• Registration Number: NCT04262479
• Lead Sponsor: Norwegian University of Science and Technology

Brief Summary

This study will evaluate the effects of 3 intra-nodal injections of GAD-alum (Diamyd), together with oral vitamin D supplementation. Safety and feasibility of the treatment will be evaluated and also effects on the immune system and on the preservation of endogenous insulin production.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-05
• Study First Submitted QC: 2020-02-06
• Study First Posted: 2020-02-10
• Study Start: 2020-03-02
• Status Verified: 2022-05
• Primary Completion: 2022-05-05
• Study Completion: 2022-05-05
• Last Update Submitted: 2022-05-25
• Last Update Posted: 2022-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

1. Signed informed consent by the patient.
2. Diagnosis of LADA and diabetes debut within the last 18 months before inclusion. LADA should be defined by the criteria of age ≥30 years at the onset of diabetes, anti-GAD positivity and no clinical need for permanent insulin treatment during the first 3 months after the diagnosis of diabetes.
3. Fasting C-peptid levels ≥ 0.3 nmol/l
4. High GADA titers (>190 U/ml)
5. Patients must be insulin independent at baseline by clinical judgement and C-peptide criteria
6. Antidiabetic medication in the form of metformin is acceptable for inclusion as well as medications not mentioned under exclusion criteria
7. Females must agree to avoid pregnancy, and must have a negative urine pregnancy test.

Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of GAD-alum. Adequate contraception is as follows:

For females of childbearing potential:

1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives
2. combined (estrogen and progestogen containing)
3. oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation
4. intrauterine device
5. intrauterine hormone-releasing system (for example, progestin-releasing coil)
6. bilateral tubal occlusion
7. vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)
8. male partner using condom
9. abstinence from heterosexual intercourse

For males of childbearing potential:

1. condom (male)
2. abstinence from heterosexual intercourse

Exclusion Criteria

1. Current or previous treatment with immunosuppressant therapy (topical or inhaled steroids are accepted)
2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
3. Systemic treatment with glucocorticoids
4. Treatment with any vaccine, including influenza vaccine, within 1 month prior to planned first study drug dose or planned treatment with any vaccine up to 1 month after the last injection with study drug
5. Antidiabetic medication (metformin excepted)
6. Significantly abnormal hematology results at screening (i.e. anemia with hemoglobin < 12 g/L).
7. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
8. Clinically significant history of acute reaction to vaccines in the past.
9. Renal disease (as defined by serum creatinine >150 µmol/l)
10. Serious cardiovascular events (myocardial infarction, stroke) within the last year preceding recruitment.
11. Participation in other clinical trials with a new chemical entity within the previous 3 months
12. A history of alcohol or drug abuse
13. Known HIV or hepatitis
14. Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study
15. Other serious chronic disease as judged by investigator.
16. Females who are lactating, are pregnant or intend to become pregnant.
17. Inability or unwillingness to comply with the provisions of this protocol
18. Deemed by the investigator not being able to follow instructions and/or follow the study protocol
19. Treatment any other supplementation of with vitamin D, marketed or not, or unwilling to abstain from such medication during the trial 120 days daily intake of Divisun (non-investigational medicinal product)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GAD-vaccination with vitamin D suppletion	recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel	Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart. Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total).
GAD-vaccination with vitamin D suppletion	Vitamin D	Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart. Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total).

Primary Outcome Measures

Name	Time	Method
injection site skin reactions	1 hour	skin reactions 1 hour post injection vs. before injection
Occurrence of adverse events (AEs)	summarized at 12 months	continuously monitored and registered
GAD65A titer in serum	at 12 months	concentration in serum after the first injection vs baseline

Secondary Outcome Measures

Name	Time	Method
Insulin secretion	5 months after first injection	measured by glucagon- and MMTT stimulated C-peptide
insulin secretion	12 months after first injection	measured by glucagon- and MMTT stimulated C-peptide
Change in maximum C-peptide during Mixed Meal Tolerance Test (MMTT)	between baseline and 5 and 12 months after the first injection
Change in HbA1c	from baseline to 5 and 12 months after the first injection
Change in fasting glucose	from baseline to 5 and 12 months after the first injection
Change in Fasting C-peptide	between baseline and 5 and 12 months after the first injection

Trial Locations

Locations (2)

Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute; 🇸🇪 Stockholm, Sweden

Department of Endocrinology, St Olavs Hospital; 🇳🇴 Trondheim, Norway