ACTIVE_NOT_RECRUITING

A Phase III Study to Investigate if the Study Drug Diamyd Can Preserve Insulin Production and Improve Glycemic Control in Patients Newly Diagnosed With Type 1 Diabetes

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The objective of DIAGNODE-3 is to evaluate the efficacy and safety of three intranodal injections of 4 μg of Diamyd compared to placebo, along with oral Vitamin D supplementation, to preserve endogenous beta cell function and influence glycemic parameters in adolescent and adults recently diagnosed with T1D carrying the HLA DR3-DQ2 haplotype.

Official Title

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Diamyd® to Preserve Endogenous Beta Cell Function in Adolescents and Adults With Recently Diagnosed Type 1 Diabetes, Carrying the Genetic HLA DR3-DQ2 Haplotype

Quick Facts

Study Start:2022-05-19

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05018585

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 28 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Must be capable of providing written, signed, and dated informed consent; and for patients who are minors, age-appropriate assent (performed according to local regulations) and parent/caregiver consent. 2. Males and females aged ≥12 and \<29 years old at the time of Screening. 3. Diagnosed with T1D (according to the American Diabetes Association \[ADA\] classification) ≤6 months at the time of Screening (V1A). 4. Possess the HLA DR3-DQ2 haplotype (all patients will be tested; prior genetic testing results will not be accepted). 5. Fasting C-peptide ≥0.12 nmol/L (≥0.36 ng/mL) on at least one occasion prior to randomization. 6. Possess detectable circulating GAD65 antibodies (lowest level of detection defined by the method used by the central laboratory). 7. Possess HbA1c levels between 35 to 80 mmol/mol (5.4 to 9.5%) on at least one occasion prior to randomization. 8. Be on a stable basal insulin dose for one month prior to inclusion with limited fluctuation of daily basal insulin requirement based on investigator's assessment. For example, if the average basal insulin dose/kg/24h over a 7-day period compared to the previous 7-day period does not vary more than approximately 20% and/or if the daily basal insulin dose does not vary more than 0.1 U/kg/24h, the dose can be considered stable. Individuals that are diagnosed with T1D according to the ADA classification but are not taking insulin are eligible to participate. 9. i. Females of childbearing potential (FOCBP) must agree to avoid pregnancy and have a negative pregnancy test performed at the required study visits. * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: * Oral. * Intravaginal. * Transdermal. * Progestogen-only hormonal contraception associated with inhibition of ovulation: * Oral. * Injectable. * Implantable. * Intrauterine device. * Intrauterine hormone-releasing system. * Bilateral tubal occlusion. * Vasectomized partner (vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the FOCBP trial patient and that the vasectomized partner has received medical assessment of the surgical success). * Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient). * Condom (male). * Abstinence from heterosexual intercourse. * Vasectomy. The agreement to remain abstinent or use two effective methods of birth control will be clearly defined in the informed consent; the patient or legally authorized representatives (e.g., parents, caregivers, or legal guardians) must sign this specific section.	1. Participation in any other trial aimed to influence beta cell function from time of diagnosis of T1D. 2. Treatment with any oral or non-insulin injectable anti-diabetic medication or other substance used with the intention to preserve beta cell function (e.g., Verapamil, GABA etc.) within 3 months prior to Randomization. 3. History of maturity-onset diabetes of the young (MODY). 4. Pancreatic surgery, chronic pancreatitis, or other pancreatic disorders that could result in decreased beta cell capacity (e.g., pancreatogenous diabetes). 5. Occurrence of DKA or severe hypoglycemia requiring hospitalization in the period of 90 days prior to Randomization (Visit 2). 6. Signs or symptoms suggesting very poorly controlled diabetes e.g., ongoing weight loss, polyuria or polydipsia. 7. Hematologic condition that would make HbA1c uninterpretable including: 1. Hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis. 2. Donation of blood or blood products to a blood bank, blood transfusion or participation in a clinical study requiring withdrawal of \>400 mL of blood during the 8 weeks prior to the Screening visit. 3. Significant iron deficiency anemia. 4. Heart malformations or vaso-occlusive crisis (VOC) leading to increased turnover of erythrocytes. 8. (US ONLY) Clinically significant abnormal hematology results at the time of Screening, specifically any of the following: white blood cells: \< 3.5 x 109/L or \>15 x 109/L; platelets: \<124 x 109/ L hemoglobin: \<10.5 g/dL 9. Treatment with marketed or over-the-counter Vitamin D at the time of Screening (V1C) and unwilling to abstain from such medication during the 120 days when the patient will be supplemented with the trial-provided Vitamin D. A patient currently taking Vitamin D at the time of Screening (V1C) must be willing to switch to the trial-provided Vitamin D treatment and to administer it per the trial requirements. 10. (US ONLY) History of hyperparathyroidism, hypercalcemia and/or nephrolithiasis, unless appropriately treated, or any other contraindication to use of Vitamin D. 11. Any clinically significant history of an acute reaction to a vaccine or its constituents (e.g., Alhydrogel). 12. Treatment with any (live or inactive) vaccine, including influenza vaccine and Coronavirus Disease 2019 (COVID-19) vaccine, within 4 weeks prior to planned first trial dose of trial drug; or planned treatment with any vaccine up to 4 weeks after the last injection with trial drug. 13. Any acute or chronic skin infection or condition that would preclude intralymphatic injection. 14. Recent (past 12 months) or current treatment with Teplizumab (TZIELD®) or with immunosuppressant therapy, including chronic use of systemic glucocorticoid therapy. Inhaled, topical, and intranasal steroid use is acceptable. Short courses (e.g., ≤5 days) of oral, intra-articular injections or injections of steroids will be permitted during the trial. 15. Continuous/chronic treatment with prescribed or over-the-counter anti-inflammatory therapies. Short-term use (e.g., \<7 days) is permissible, for example to treat a headache or in connection with a fever. 16. Known or suspected acute infection, including COVID-19 or influenza, at the time of Randomization or within 4 weeks prior to Randomization. 17. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles. 18. Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection. Patients with previous hepatitis C infection that is now cured may be eligible. 19. 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, neurological (including Batten disease), significant diabetes complication, any underlying conditions or receiving treatments that could affect red blood cell turnover or other diseases that in the opinion of the investigator would interfere with trial participation or procedures. Celiac disease or elevated transglutaminase antibody titers is not a reason for exclusion. 20. (US ONLY) Significant cardiovascular disease (including inadequately controlled hypertension \[resting blood pressure \>140/90 mmHg despite treatment\], history of myocardial infarction, angina, use of anti-anginal medicines \[e.g., nitroglycerin\], or abnormal cardiac stress test. 21. History of significant hepatic disease or Screening alanine aminotransferase (ALT) \>2.5 x upper limit of normal (ULN) or aspartate aminotransferase (AST) 3 x ULN and/or total bilirubin \>2 x ULN. Patients with documented Gilbert syndrome and total bilirubin level ≥2 x ULN due to unconjugated hyperbilirubinemia, without other hepatic impairment, are permitted. 22. Estimated glomerular filtration rate (eGFR) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) for those \>18 years, or by the Schwartz equation for those 12 to 18 years old, \<60 mL/min per 1.73 m or rapidly progressing renal disease. 23. Patients diagnosed with hypothyroidism or hyperthyroidism must be on stable treatment for at least 3 months prior to Randomization (with normal free thyroxine \[T4\] levels if hypothyroid). 24. Any clinically significant abnormal findings during Screening, and any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient's safety or ability to complete the trial. 25. History of malignancy not in remission within the last 5 years other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ. 26. Patients with any mental condition rendering him/her unable to understand the nature, scope and possible consequences of the trial, and/or evidence of poor compliance with medical instructions at Screening or showing non-compliance during the Run-In Period. 27. A history of alcohol or drug abuse or dependence within the past 12 months based on DSM IV criteria. 28. Previous treatment with the active substance recombinant human GAD65. 29. Participation in a clinical trial involving administration of an investigational drug in the past 3 months or 5 half-lives (whichever is longer) prior to first dosing of trial drug or during the trial. 30. Females who are breastfeeding, pregnant or plan to become pregnant during the trial. 31. Patients who in the opinion of the investigator will not be able to follow instructions and/or follow the trial procedures or patients that are unwilling or unable to comply with the provisions of this protocol. 32. An employee or immediate family member of an employee of Diamyd Medical AB. 33. (US ONLY)For subjects aged 18 years and older, a body mass index (BMI) ≥30 kg/m2 or ≤18.5 kg/m2; for subjects aged under 18 years BMI ≥95th percentile or ≤5th percentile for age and sex according to the US Centre for Disease Control and Prevention at V1B. (For subjects aged 18 years and older with a BMI ≥25 to ≤30 kg/m2, and for subjects aged under 18 years with a BMI ≥85th to ≤95th percentile, re-confirmation of Type 1 Diabetes diagnoses by an external, independent endocrinologist is required prior to randomization.)

Inclusion Criteria

Exclusion Criteria

1. Must be capable of providing written, signed, and dated informed consent; and for patients who are minors, age-appropriate assent (performed according to local regulations) and parent/caregiver consent.
2. Males and females aged ≥12 and \<29 years old at the time of Screening.
3. Diagnosed with T1D (according to the American Diabetes Association \[ADA\] classification) ≤6 months at the time of Screening (V1A).
4. Possess the HLA DR3-DQ2 haplotype (all patients will be tested; prior genetic testing results will not be accepted).
5. Fasting C-peptide ≥0.12 nmol/L (≥0.36 ng/mL) on at least one occasion prior to randomization.
6. Possess detectable circulating GAD65 antibodies (lowest level of detection defined by the method used by the central laboratory).
7. Possess HbA1c levels between 35 to 80 mmol/mol (5.4 to 9.5%) on at least one occasion prior to randomization.
8. Be on a stable basal insulin dose for one month prior to inclusion with limited fluctuation of daily basal insulin requirement based on investigator's assessment. For example, if the average basal insulin dose/kg/24h over a 7-day period compared to the previous 7-day period does not vary more than approximately 20% and/or if the daily basal insulin dose does not vary more than 0.1 U/kg/24h, the dose can be considered stable. Individuals that are diagnosed with T1D according to the ADA classification but are not taking insulin are eligible to participate.
9. i. Females of childbearing potential (FOCBP) must agree to avoid pregnancy and have a negative pregnancy test performed at the required study visits.
* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
* Oral.
* Intravaginal.
* Transdermal.
* Progestogen-only hormonal contraception associated with inhibition of ovulation:
* Oral.
* Injectable.
* Implantable.
* Intrauterine device.
* Intrauterine hormone-releasing system.
* Bilateral tubal occlusion.
* Vasectomized partner (vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the FOCBP trial patient and that the vasectomized partner has received medical assessment of the surgical success).
* Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient).
* Condom (male).
* Abstinence from heterosexual intercourse.
* Vasectomy. The agreement to remain abstinent or use two effective methods of birth control will be clearly defined in the informed consent; the patient or legally authorized representatives (e.g., parents, caregivers, or legal guardians) must sign this specific section.

1. Participation in any other trial aimed to influence beta cell function from time of diagnosis of T1D.
2. Treatment with any oral or non-insulin injectable anti-diabetic medication or other substance used with the intention to preserve beta cell function (e.g., Verapamil, GABA etc.) within 3 months prior to Randomization.
3. History of maturity-onset diabetes of the young (MODY).
4. Pancreatic surgery, chronic pancreatitis, or other pancreatic disorders that could result in decreased beta cell capacity (e.g., pancreatogenous diabetes).
5. Occurrence of DKA or severe hypoglycemia requiring hospitalization in the period of 90 days prior to Randomization (Visit 2).
6. Signs or symptoms suggesting very poorly controlled diabetes e.g., ongoing weight loss, polyuria or polydipsia.
7. Hematologic condition that would make HbA1c uninterpretable including:
1. Hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis.
2. Donation of blood or blood products to a blood bank, blood transfusion or participation in a clinical study requiring withdrawal of \>400 mL of blood during the 8 weeks prior to the Screening visit.
3. Significant iron deficiency anemia.
4. Heart malformations or vaso-occlusive crisis (VOC) leading to increased turnover of erythrocytes.
8. (US ONLY) Clinically significant abnormal hematology results at the time of Screening, specifically any of the following: white blood cells: \< 3.5 x 109/L or \>15 x 109/L; platelets: \<124 x 109/ L hemoglobin: \<10.5 g/dL
9. Treatment with marketed or over-the-counter Vitamin D at the time of Screening (V1C) and unwilling to abstain from such medication during the 120 days when the patient will be supplemented with the trial-provided Vitamin D. A patient currently taking Vitamin D at the time of Screening (V1C) must be willing to switch to the trial-provided Vitamin D treatment and to administer it per the trial requirements.
10. (US ONLY) History of hyperparathyroidism, hypercalcemia and/or nephrolithiasis, unless appropriately treated, or any other contraindication to use of Vitamin D.
11. Any clinically significant history of an acute reaction to a vaccine or its constituents (e.g., Alhydrogel).
12. Treatment with any (live or inactive) vaccine, including influenza vaccine and Coronavirus Disease 2019 (COVID-19) vaccine, within 4 weeks prior to planned first trial dose of trial drug; or planned treatment with any vaccine up to 4 weeks after the last injection with trial drug.
13. Any acute or chronic skin infection or condition that would preclude intralymphatic injection.
14. Recent (past 12 months) or current treatment with Teplizumab (TZIELD®) or with immunosuppressant therapy, including chronic use of systemic glucocorticoid therapy. Inhaled, topical, and intranasal steroid use is acceptable. Short courses (e.g., ≤5 days) of oral, intra-articular injections or injections of steroids will be permitted during the trial.
15. Continuous/chronic treatment with prescribed or over-the-counter anti-inflammatory therapies. Short-term use (e.g., \<7 days) is permissible, for example to treat a headache or in connection with a fever.
16. Known or suspected acute infection, including COVID-19 or influenza, at the time of Randomization or within 4 weeks prior to Randomization.
17. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles.
18. Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection. Patients with previous hepatitis C infection that is now cured may be eligible.
19. 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, neurological (including Batten disease), significant diabetes complication, any underlying conditions or receiving treatments that could affect red blood cell turnover or other diseases that in the opinion of the investigator would interfere with trial participation or procedures. Celiac disease or elevated transglutaminase antibody titers is not a reason for exclusion.
20. (US ONLY) Significant cardiovascular disease (including inadequately controlled hypertension \[resting blood pressure \>140/90 mmHg despite treatment\], history of myocardial infarction, angina, use of anti-anginal medicines \[e.g., nitroglycerin\], or abnormal cardiac stress test.
21. History of significant hepatic disease or Screening alanine aminotransferase (ALT) \>2.5 x upper limit of normal (ULN) or aspartate aminotransferase (AST) 3 x ULN and/or total bilirubin \>2 x ULN. Patients with documented Gilbert syndrome and total bilirubin level ≥2 x ULN due to unconjugated hyperbilirubinemia, without other hepatic impairment, are permitted.
22. Estimated glomerular filtration rate (eGFR) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) for those \>18 years, or by the Schwartz equation for those 12 to 18 years old, \<60 mL/min per 1.73 m or rapidly progressing renal disease.
23. Patients diagnosed with hypothyroidism or hyperthyroidism must be on stable treatment for at least 3 months prior to Randomization (with normal free thyroxine \[T4\] levels if hypothyroid).
24. Any clinically significant abnormal findings during Screening, and any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient's safety or ability to complete the trial.
25. History of malignancy not in remission within the last 5 years other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ.
26. Patients with any mental condition rendering him/her unable to understand the nature, scope and possible consequences of the trial, and/or evidence of poor compliance with medical instructions at Screening or showing non-compliance during the Run-In Period.
27. A history of alcohol or drug abuse or dependence within the past 12 months based on DSM IV criteria.
28. Previous treatment with the active substance recombinant human GAD65.
29. Participation in a clinical trial involving administration of an investigational drug in the past 3 months or 5 half-lives (whichever is longer) prior to first dosing of trial drug or during the trial.
30. Females who are breastfeeding, pregnant or plan to become pregnant during the trial.
31. Patients who in the opinion of the investigator will not be able to follow instructions and/or follow the trial procedures or patients that are unwilling or unable to comply with the provisions of this protocol.
32. An employee or immediate family member of an employee of Diamyd Medical AB.
33. (US ONLY)For subjects aged 18 years and older, a body mass index (BMI) ≥30 kg/m2 or ≤18.5 kg/m2; for subjects aged under 18 years BMI ≥95th percentile or ≤5th percentile for age and sex according to the US Centre for Disease Control and Prevention at V1B. (For subjects aged 18 years and older with a BMI ≥25 to ≤30 kg/m2, and for subjects aged under 18 years with a BMI ≥85th to ≤95th percentile, re-confirmation of Type 1 Diabetes diagnoses by an external, independent endocrinologist is required prior to randomization.)

Contacts and Locations

Principal Investigator

Johnny Ludvigsson, Professor

PRINCIPAL_INVESTIGATOR

Crown Princess Victoria Children´s Hospital and Linköping University

Study Locations (Sites)

Mary and Dick Allen Diabetes Center at Hoag Hospital

Newport Beach, California, 92663

United States

Stanford University School of Medicine Center for Academic Medicine

Palo Alto, California, 94304

United States

UCSD/ Rady Children's Hospital

San Diego, California, 92123

United States

University of Colorado Anschutz Medical Campus, Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, 80045

United States

Diabetes Research Institute (DRI)-University of Miami Leonard M. Miller School of Medicine (UMMSM)

Miami, Florida, 33136

United States

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, 83404

United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242

United States

Johns Hopkins University

Baltimore, Maryland, 21287

United States

Joslin Diabetes Center

Boston, Massachusetts, 02215

United States

Washington University Diabetes Center at Barnes Jewish Hospital

St Louis, Missouri, 63110

United States

Hassenfeld Children's Hospital at NYU Langone Health, Pediatric Diabetes Center

New York, New York, 10016

United States

Amarillo Medical Specialists

Amarillo, Texas, 79124

United States

Diabetes & Glandular Disease Clinic

San Antonio, Texas, 78237

United States

Collaborators and Investigators

Sponsor: Diamyd Medical AB

Johnny Ludvigsson, Professor, PRINCIPAL_INVESTIGATOR, Crown Princess Victoria Children´s Hospital and Linköping University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-05-19

Study Completion Date2027-12

Study Record Updates

Study Start Date2022-05-19

Study Completion Date2027-12

Terms related to this study

Keywords Provided by Researchers

Diabetes Mellitus
residual beta cell function
HLA DR3-DQ2
Diabetes Mellitus, Type 1
Autoimmune Diseases
Metabolic Disease
Autoimmune Diabetes
Vitamin D
Immune System Diseases
Insulin Dependent Diabetes
rhGAD65
GAD65
GAD-alum
residual c-peptide
T1D
recent-onset T1D
Type 1 Diabetes
HLA
Diamyd
Diabetes
Newly Diagnosed
New onset
DIAGNODE-3
GAD
Diamyd GAD
Intralymphatic injections
Diabetes immunotherapy
Immunotherapy
Antigen-specific

Additional Relevant MeSH Terms

Type 1 Diabetes Mellitus

A Phase III Study to Investigate if the Study Drug Diamyd Can Preserve Insulin Production and Improve Glycemic Control in Patients Newly Diagnosed With Type 1 Diabetes

Conditions

Quick Navigation

Study Overview

Description

Official Title

Quick Facts

Study ID

Participation Criteria

Contacts and Locations

Principal Investigator

Study Locations (Sites)

Collaborators and Investigators

Study Record Dates

Study Registration Dates

Study Record Updates

Terms related to this study

Keywords Provided by Researchers

Additional Relevant MeSH Terms