Study to Evaluate the Safety and Feasibility of Diamyd® in Individuals at Risk for Type 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

DiaPrecise, A Phase II Open Label Study to Evaluate the Safety and Feasibility of Intralymphatic Administration of Diamyd® in Individuals at Risk for Type 1 Diabetes Carrying the HLA DR3-DQ2 Haplotype

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05683990
• Other study ID #: DiaPrecise (D/P2/22/8)
• Status: Recruiting
• Phase: Phase 2
• Start date: November 14, 2023
• Est. completion date: February 28, 2025

Study information

• Verified date: November 2023
• Source: Diamyd Medical AB
• Contact: Chief Operating Officer
• Phone: +46 (0) 8 661 00 26
• Email: clinicaltrials[@]diamyd.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A 2-arm randomized Phase II Open Label Study to evaluate the safety and feasibility of intralymphatic administration of Diamyd® (Diamyd) in individuals at risk of Type 1 diabetes carrying the HLA DR3-DQ2 haplotype.

Description:

The trial is a 2-arm, randomized, open label clinical trial in individuals aged 8 - <18 years with HLA DR3-DQ2 and multiple islet autoantibodies (Stage 1 or Stage 2) at increased risk for T1D. At baseline eligible individuals at risk of T1D will be randomized 1:1 into 2 or 3 injections of Diamyd® administered into an inguinal lymph node. Subjects will be followed for a total of 12 months post-enrollment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: February 28, 2025
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Written informed consent/assent from the individual and the individual's parents or caretaker(s) according to local regulations.

2. Males and females aged =8 and <18 years old at the time of Screening.

3. Possess the HLA DR3-DQ2 haplotype.

4. Seropositive for GADA and at least one additional T1D-associated autoantibody (IA-2A, ZnT8A or IAA).

Exclusion Criteria:

1. Diagnosis of T1D (stage 3 T1D, according to the American Diabetes Association [ADA] classification).

2. Fasting glucose > 7 mmol/L (126 mg/dl), 2-hour-OGTT plasma glucose > 11.1 mmol/L (200 mg/dL) or HbA1c > 6.5% (48 mmol/mol) at the screening Visit.

3. Treatment with any anti-diabetic medication, including the use of external insulin.

4. Participation in any other clinical trial testing pharmaceutical treatments.

5. Recent (past 12 months) or current treatment with immunosuppressant therapy, including chronic use of glucocorticoid therapy. Inhaled, topical, and intranasal steroid use is acceptable. Short courses (e.g., =5 days) of oral or intra-articular injections of steroids will be permitted on trial.

6. History of hyperparathyroidism, hypercalcemia and/or nephrolithiasis, unless appropriately treated, or any other contraindication to use of Vitamin D.

7. History of epilepsy, serious head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles

8. Any clinically significant history of an acute reaction to a vaccine or its constituents (e.g., Alhydrogel) or lidocaine (local anesthetic)

9. Any acute or chronic skin infection or condition that would preclude intralymphatic injection.

10. Treatment with any (live or inactive) vaccine, including influenza vaccine and Coronavirus Disease 2019 (COVID-19) vaccine, within 4 weeks prior to planned first dose of study drug; or planned treatment with any vaccine up to 4 weeks after the last injection with study drug.

11. Ongoing diagnosed post-COVID19 syndrome.

12. Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection. Individuals with previous hepatitis C infection that is now cured may be eligible.

13. Any clinically significant concomitant medical condition, including but not limited to other autoimmune diseases, cardiovascular, gastrointestinal, hematological, immune, renal including a history of renal transplantation or neurological that in the opinion of the investigator would interfere with trial participation or procedures. Celiac disease with adequate diet as well as stable autoimmune thyroiditis will be permitted.

14. Any clinically significant abnormal findings detected during Screening that might jeopardize the individual's safety or ability to complete the trial.

15. Females who are lactating or pregnant (for females who have started menstruating the possibility of pregnancy must be excluded by urine ßHCG onsite prior to the study drug administration).

16. Males or females not willing to use adequate contraception, if sexually active, until 90 days after the last Diamyd administration. Adequate contraception is as follows:

For females of childbearing potential (FOCBP)

1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives

2. intrauterine device

3. intrauterine system (for example, progestin-releasing coil)

4. refraining from heterosexual intercourse if that is the preferred and usual lifestyle of the subject.

For sexually active males

1. condom

2. Abstinence from heterosexual intercourse if that is the preferred and usual lifestyle of the subject.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Prevention

Intervention

Drug:
• Diamyd
4 µg (0.1 mL) of Diamyd administered 1 month apart.

Locations

Country	Name	City	State
Sweden	Lund University/CRC, Skåne University Hospital,	Malmö

Sponsors (1)

Lead Sponsor	Collaborator
Diamyd Medical AB

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of AEs (including Injection site reactions) and SAEs		From screening to 12 months.
Primary	Number of Clinically Significant Abnormal Results from Physical examinations, including neurological and Vital Signs assessments		From screening to 12 months.
Primary	Number of Clinically Significant Abnormal Results From Laboratory measurements, including hematology, clinical chemistry, metabolic status parameters (fasting C-peptide, HbA1c, fasting glucose) and urine analysis		From screening to 12 months.
Secondary	Stage progression	Number of individuals progressing from stage 1 to stage 2 and from stage 2 to stage 3.	From screening to 12 months.
Secondary	T1D diagnosis	Time to T1D diagnosis.	From screening to 12 months.
Secondary	Time to stage progression	Time from stage 1 to stage 2 and time from stage 2 to stage 3.	From screening to 12 months.
Secondary	OGTT stimulated C-peptide	Change in C-peptide /insulin /glucose (Area Under the Curve [AUC]mean 0-120 min) during a 2-hour Oral Glucose Tolerance Test (OGTT) from screening to 12 months.	From screening to 12 months.
Secondary	Change in Hemoglobin A1c (HbA1c)	Change in Hemoglobin A1c (HbA1c) from baseline to 12 months.	From baseline to 12 months.
Secondary	Change in time in glycemic target range	Change in time in glycemic target range 3.9 to 10 mmol/L (70 to 180 mg/dL) and 3.9 to 7.8 mmol/L (70 to 140 mg/dL) evaluated from continuous glucose monitoring (CGM) data from screening to 12 months.	From screening to 12 months.
Secondary	Change in time in range > 13.9 mmol/L	Change in time in range > 13.9 mmol/L (> 250 mg/dL) evaluated from CGM data from screening to 12 months.	From screening to 12 months.
Secondary	Change in time in range > 10 mmol/L	Change in time in range > 10 mmol/L (> 180 mg/dL) evaluated from CGM data from screening to 12 months.	From screening to 12 months.
Secondary	Change in time in range > 7.8 mmol/L	Change in time in range > 7.8 mmol/L (> 140 mg/dL) evaluated from CGM data from screening to 12 months.	From screening to 12 months.
Secondary	Change in glycemic variation	Change in glycemic variation (Coefficient of variation [CV], SD) evaluated from CGM data from screening to 12 months.	From screening to 12 months.
Secondary	Variables that indicate effects on the immune system	Variables that indicate effects on the immune system such as the concentration of serum autoantibodies.	From baseline to 12 months.