A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 (TOPPLE T1D)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04279613 |
Recruitment Status :
Recruiting
First Posted : February 21, 2020
Last Update Posted : November 3, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Type I Diabetes | Drug: NNC0361-0041 Other: Placebo | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 48 participants |
Allocation: | Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | The trial is a placebo-controlled, double-blinded within cohorts, randomized, multiple ascending dose trial with a sequential trial design. A total of 48 patients with T1D are planned to be studied in 4 cohorts of 12 patients (9 on active and 3 on placebo treatment). |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 Administered Subcutaneously to Patients With Type 1 Diabetes Mellitus |
Actual Study Start Date : | November 23, 2020 |
Estimated Primary Completion Date : | January 31, 2024 |
Estimated Study Completion Date : | January 31, 2024 |

Arm | Intervention/treatment |
---|---|
Experimental: NNC0361-0041
Dosage form: 9 mg/ml Solution for injection Route of administration: Subcutaneous Initial dose/Unit dose strength(s)/Dosage level(s) in cohort 1: 1mg Additional doses in cohorts 2, 3, and 4: 5mg, 12.5mg and 25mg Dosing instructions: Once weekly on site
|
Drug: NNC0361-0041
Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2) is administered s.c. via syringe and needle. |
Placebo Comparator: Placebo
Dosage form: Solution for injection Route of administration: Subcutaneous Dosing instructions: Once weekly on site
|
Other: Placebo
Placebo |
- Adverse Events [ Time Frame: 1 year ]Number of adverse events recorded from the time of first dosing (Day 1) and until completion of the follow-up visit #17
- Change in the area under the plasma C-peptide concentration-time curve [ Time Frame: 3 months ]Relative change in the area under the plasma C-peptide concentration-time curve from time 0 to 2 hours during MMTT from baseline to 3 months between groups

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 45 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Willing to provide Informed Consent
- Participants must live in a location with rapid access to emergency medical services
- Age 18-45 years (both inclusive) at the time of signing informed consent
- Must have a diagnosis of T1D for less than 48 months at randomization
- Must have at least one diabetes-related autoantibody present (GAD65A; mIAA, if obtained within 10 days of the onset of insulin therapy; IA-2A; ICA; or ZnT8A)
- Must have stimulated C-peptide levels greater than or equal to 0.2 pmol/ml measured during an MMTT conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization
- Be willing to comply with intensive diabetes management
- HbA1c ≤8.5% at screening
- Subjects who are CMV and/or EBV seronegative at screening must be CMV and/or EBV PCR negative within 37 days of randomization and may not have had signs or symptoms of a CMV and/or EBV compatible illness lasting longer than 7 days within 37 days of randomization
- Be up to date on recommended immunizations
- Be at least 6 weeks from last live immunization
- Be at least 4 weeks from killed vaccine other than flu vaccine
- Participants are required to receive killed influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available
- Be willing and medically acceptable to postpone live vaccines during the treatment period and for 3 months following last dose of study drug
- If participant is female with reproductive potential, she must have a negative pregnancy test at screening and be willing to avoid pregnancy using a highly effective contraceptive method for the 12 months of the study
- Males of reproductive age must use adequate contraceptive method during the treatment phase and for 3 months following last dose of study drug
- Participants are required to receive an authorized non-live COVID-19 vaccination and be fully vaccinated, including eligible boosters as indicated, at least two weeks prior to randomization.
Exclusion Criteria:
Potential participants must not meet any of the following exclusion criteria:
-
One or more screening laboratory values as stated
- Leukocytes < 3,000/μL
- Neutrophils <1,500 /μL
- Lymphocytes <800 /μL
- Platelets <100,000 /μL
- Haemoglobin <6.2 mmol/L (10.0 g/dL)
- Potassium >5.5 mmol/L or <3.0 mmol/L
- Sodium >150mmol/L or < 130mmol/L
- AST or ALT ≥2.5 times the upper limits of normal
- Bilirubin ≥ 1.5 times upper limit of normal
- Glomerular Filtration Rate (eGFR) value of eGFR < 60 ml/min/1.73 m2 as defined by KDIGO 2012 (43)
- Any other laboratory abnormality that might, in the judgment of the investigator, place the subject at unacceptable risk for participation in this trial
- Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening
- Use of other immunosuppressive agents including chronic use of systemic steroids. Topical products are acceptable (nasal, conjunctival, skin)
- Have active signs or symptoms of acute infection at the time of randomization
- Have current, confirmed COVID-19 infection
- Chronic active infection other than localized skin infections
- Have evidence of prior or current tuberculosis infection as assessed by PPD, interferon gamma release assay or by history
- Have evidence of current or past HIV, Hepatitis B infection
- Have evidence of active Hepatitis C infection
- Vaccination with a live virus within the last 6 weeks and killed vaccine within 4 weeks (except 2 weeks for flu vaccine)
- Be currently pregnant or lactating, or anticipate getting pregnant within the one-year study period.
- Have severe obesity: adults BMI ≥ 40
- Have a history of malignancies
- Untreated hypothyroidism or active Graves' disease
- History of severe reaction to prior vaccination
- Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days after last blood draw (or 5 half-lives of investigational drug, whichever is greater) before screening, or currently enrolled in any other clinical trial
- Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the trial
- Supine blood pressure at screening outside the range of 90-139 mmHg for systolic or 50-89 mmHg for diastolic. To exclude white-coat nervousness a single repeat measurement is allowed
- Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk
- Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04279613
Contact: Lisa Rafkin, MS | 305-243-6146 | LRafkin@med.miami.edu | |
Contact: Ryan O'Donnell, MS | Ryan.O'Donnell@epi.usf.edu |
United States, California | |
Children's Hospital of Orange County | Recruiting |
Orange, California, United States, 92868 | |
Contact: Heather Speer 714-509-8613 HSpeer@choc.org | |
Principal Investigator: Mark Daniels, MD | |
University of California - San Francisco | Recruiting |
San Francisco, California, United States, 94143 | |
Contact: Rebecca Wesch 415-476-5984 rebecca.wesch@ucsf.edu | |
Contact: Karen Ko 415-514-3730 karen.ko@ucsf.edu | |
Principal Investigator: Stephen Gitelman, MD | |
Stanford University | Recruiting |
Stanford, California, United States, 94305 | |
Contact: Trudy Esrey 650-498-4450 tesrey@stanford.edu | |
Principal Investigator: Darrell Wilson, MD | |
United States, Colorado | |
Barbara Davis Center at University of Colorado Anschutz Medical Campus | Recruiting |
Aurora, Colorado, United States, 80045 | |
Contact: Morgan Sooy 303-724-5686 MORGAN.QUIST@CUANSCHUTZ.EDU | |
Principal Investigator: Andrea Steck, MD | |
United States, Connecticut | |
Yale University School of Medicine | Recruiting |
New Haven, Connecticut, United States, 06519 | |
Contact: Laurie Feldman 203-737-2760 laurie.feldman@yale.edu | |
Principal Investigator: Kevan Herold, MD, Ph.D. | |
United States, Florida | |
University of Florida | Recruiting |
Gainesville, Florida, United States, 32610 | |
Contact: Jennifer Hosford 352-294-5759 jennifer.hosford@peds.ufl.edu | |
Principal Investigator: Michael Haller, MD | |
United States, Georgia | |
Emory Children's Center | Recruiting |
Atlanta, Georgia, United States, 30329 | |
Contact: Xiaomiao Lan-Pidhainy 404-712-0051 xlanpid@emory.edu | |
Principal Investigator: Andrew Muir, MD | |
United States, Indiana | |
Indiana University - Riley Hospital for Children | Recruiting |
Indianapolis, Indiana, United States, 46202 | |
Contact: Maria Spall 317-278-8879 malnicho@iu.edu | |
Principal Investigator: Linda DiMeglio, MD | |
United States, Massachusetts | |
Joslin Diabetes Center | Recruiting |
Boston, Massachusetts, United States, 02215 | |
Contact: Jason Gaglia, MD 888-813-8669 TrialNet@joslin.harvard.edu | |
Principal Investigator: Jason Gaglia, MD | |
United States, Minnesota | |
Regents of the University of Minnesota | Recruiting |
Minneapolis, Minnesota, United States, 55466 | |
Contact: Janice Leschyshyn 612-626-8467 lesch004@umn.edu | |
Principal Investigator: Antoinette Moran, MD | |
United States, Missouri | |
The Children's Mercy Hospital | Recruiting |
Kansas City, Missouri, United States, 64108 | |
Contact: Jennifer James 913-696-5059 jljames@cmh.edu | |
Principal Investigator: Wayne Moore, MD | |
United States, New York | |
The Naomi Berrie Diabetes Center at Columbia University Medical Center | Recruiting |
New York, New York, United States, 10032 | |
Contact: Sarah Pollak 212-851-5425 sjp2174@columbia.edu | |
Principal Investigator: Robin Goland, MD | |
United States, Pennsylvania | |
University of Pittsburgh | Recruiting |
Pittsburgh, Pennsylvania, United States, 15224 | |
Contact: Kelli DeLallo 412-692-5210 kelli.delallo@chp.edu | |
Principal Investigator: Dorothy Becker, MD | |
United States, Tennessee | |
Vanderbilt Eskind Diabetes Center | Recruiting |
Nashville, Tennessee, United States, 37232 | |
Contact: Faith Brendle 615-936-8638 faith.brendle@vumc.org | |
Principal Investigator: William Russell, MD | |
United States, Texas | |
University of Texas Southwestern Medical Center | Recruiting |
Dallas, Texas, United States, 75390 | |
Contact: Serey Sao 214-648-3061 serey.sao@utsouthwestern.edu | |
Contact: Lindsay Harter Lindsay.Harter@UTSouthwestern.edu | |
Principal Investigator: Perrin White, MD | |
United States, Washington | |
Benaroya Research Institute | Recruiting |
Seattle, Washington, United States, 98101 | |
Contact: Corinna Tordillos 206-341-8937 ctordillos@benaroyaresearch.org | |
Principal Investigator: Carla Greenbaum, MD |
Study Chair: | Robin Goland, MD | Type 1 Diabetes TrialNet | |
Study Director: | Carla Greenbaum, MD | Type 1 Diabetes TrialNet |
Responsible Party: | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
ClinicalTrials.gov Identifier: | NCT04279613 |
Other Study ID Numbers: |
TN27 Immunoplasmid Therapy UC4DK117009 ( U.S. NIH Grant/Contract ) |
First Posted: | February 21, 2020 Key Record Dates |
Last Update Posted: | November 3, 2022 |
Last Verified: | November 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Data will be available at the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) Central Repository |
URL: | https://repository.niddk.nih.gov/home/ |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Diabetes Mellitus, Type 1 Diabetes Mellitus Glucose Metabolism Disorders Metabolic Diseases |
Endocrine System Diseases Autoimmune Diseases Immune System Diseases |