Type I DiabetesPhase 1TOPPLE T1DNCT04279613
A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041
A Phase 1 study testing NNC0361-0041 in people with Type I Diabetes, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 16 sites in United States.
Trial summary
The trial is a placebo-controlled, double-blinded within cohorts, randomized, multiple ascending dose trial with a sequential trial design. The primary outcome is to investigate the safety and tolerability of ascending subcutaneous weekly doses of NNC0361-0041 plasmid in patients with T1D. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Type I Diabetes
- What is being tested?
- NNC0361-0041
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 16 sitesUnited States
- Study dates
- 23 Nov 2020to 24 Apr 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 32Show fewer
- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Emory Children's Center
Atlanta, Georgia, 30329
Barbara Davis Center at University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Joslin Diabetes Center
Boston, Massachusetts, 02215
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Florida
Gainesville, Florida, 32610
Indiana University - Riley Hospital for Children
Indianapolis, Indiana, 46202
The Children's Mercy Hospital
Kansas City, Missouri, 64108
Regents of the University of Minnesota
Minneapolis, Minnesota, 55466
Vanderbilt Eskind Diabetes Center
Nashville, Tennessee, 37232
Yale University School of Medicine
New Haven, Connecticut, 06519
The Naomi Berrie Diabetes Center at Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Orange County
Orange, California, 92868
University of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of California - San Francisco
San Francisco, California, 94143
Benaroya Research Institute
Seattle, Washington, 98101
Stanford University
Stanford, California, 94305
About this study
Official title: A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 Administered Subcutaneously to Patients With Type 1 Diabetes Mellitus
The trial is a placebo-controlled, double-blinded within cohorts, randomized, multiple ascending dose trial with a sequential trial design. The primary outcome is to investigate the safety and tolerability of ascending subcutaneous weekly doses of NNC0361-0041 plasmid in patients with T1D.
Read the detailed description
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). Within each cohort, sentinel enrollment will occur and safety assessment will occur before remaining participants are enrolled. The treatment period will be 12 weeks with once weekly dosing leading to 12 doses in total. Dose escalation will occur after data safety review (as described in section 4.9.2). An MMTT to assess insulin secretion will be done at baseline, 1, 3, 6, and 12 months. The follow-up (FU) period will be 1 week after the last dose, as well as 4, 6 and 12 months after the first dose.
- Conditions
- Type I Diabetes
- Being tested
- NNC0361-0041, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NNC0361-0041Drug
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.
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| NNC0361-0041 | Experimental | 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 Receives: Drug: NNC0361-0041 |
| Placebo | Placebo comparator | Dosage form: Solution for injection Route of administration: Subcutaneous Dosing instructions: Once weekly on site Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Number of adverse events recorded during the on-treatment period, which is defined as from first treatment through visit 15 (or 5 weeks after last treatment for subjects not receiving all injections)
Measured: 16 Weeks
Secondary outcomes (1)
Change in the Area Under the Plasma C-peptide Concentration-time Curve Across the 2-hour Test Period.
Proportional change from baseline c-peptide AUC mean from a 2-hour mixed meal tolerance test by assessment schedule. The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis.
Measured: 4-, 12-, 24- and 52-weeks from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2020
- Study start23 Nov 2020
- Primary completion31 Aug 2023
- Study completion24 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type I DiabetesStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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 blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Robin Goland, MD, Study chair, Type 1 Diabetes TrialNetCarla Greenbaum, MD, Study director, Type 1 Diabetes TrialNet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04279613
- Sponsor's protocol ID
- TN27 Immunoplasmid Therapy
- Other IDs
- UC4DK117009
- Acronym
- TOPPLE T1D
- Status last verified
- May 2025
- First submitted
- 19 Feb 2020
- Last updated
- 20 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be available at the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) Central Repository
Publications
Pang H, Chen Z, Han FY. Nano-based therapy for type 1 diabetes: from immuno-intervention to insulin delivery. Acta Biomater. 2025 Jul 1;201:101-120. doi: 10.1016/j.actbio.2025.06.016. Epub 2025 Jun 20.
PubMed 40544026Pagni PP, Chaplin J, Wijaranakula M, Wesley JD, Granger J, Cracraft J, O'Brien C, Perdue N, Kumar V, Li S, Ratliff SS, Roach A, Misquith A, Chan CL, Coppieters K, von Herrath M. Multicomponent Plasmid Protects Mice From Spontaneous Autoimmune Diabetes. Diabetes. 2021 Aug 13;71(1):157-69. doi: 10.2337/db21-0327. Online ahead of print.
PubMed 34389610
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 Administered Subcutaneously to Patients With Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT04279613
- Acronym / sponsor ID
- TOPPLE T1D / TN27 Immunoplasmid Therapy
- Conditions
- Type I Diabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- Novo Nordisk A/S
- Study start
- 23 Nov 2020 (actual)
- Primary completion
- 31 Aug 2023 (actual)
- Study completion
- 24 Apr 2024 (actual)
- First posted
- 21 Feb 2020 (actual)
- Results
- Posted 20 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The trial is a placebo-controlled, double-blinded within cohorts, randomized, multiple ascending dose trial with a sequential trial design. The primary outcome is to investigate the safety and tolerability of ascending subcutaneous weekly doses of NNC0361-0041 plasmid in patients with T1D.
Detailed description
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). Within each cohort, sentinel enrollment will occur and safety assessment will occur before remaining participants are enrolled. The treatment period will be 12 weeks with once weekly dosing leading to 12 doses in total. Dose escalation will occur after data safety review (as described in section 4.9.2). An MMTT to assess insulin secretion will be done at baseline, 1, 3, 6, and 12 months. The follow-up (FU) period will be 1 week after the last dose, as well as 4, 6 and 12 months after the first dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| NNC0361-0041 | Experimental | Drug: NNC0361-0041Dosage 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 |
| Placebo | Placebo comparator | Other: PlaceboDosage form: Solution for injection Route of administration: Subcutaneous Dosing instructions: Once weekly on site |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- 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)
Key exclusion criteria (32 listed)
- One or more screening laboratory values as stated
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NNC0361-0041Recombinant 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. | Drug | NNC0361-0041 |
| PlaceboPlacebo | Other | Placebo |
Primary outcome
Adverse Events
Time frame: 16 Weeks
Number of adverse events recorded during the on-treatment period, which is defined as from first treatment through visit 15 (or 5 weeks after last treatment for subjects not receiving all injections)
1 secondary outcome
Change in the Area Under the Plasma C-peptide Concentration-time Curve Across the 2-hour Test Period.
Time frame: 4-, 12-, 24- and 52-weeks from baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40544026Pang H, Chen Z, Han FY. Nano-based therapy for type 1 diabetes: from immuno-intervention to insulin delivery. Acta Biomater. 2025 Jul 1;201:101-120. doi: 10.1016/j.actbio.2025.06.016. Epub 2025 Jun 20.
- Derived from this study: PubMed 34389610Pagni PP, Chaplin J, Wijaranakula M, Wesley JD, Granger J, Cracraft J, O'Brien C, Perdue N, Kumar V, Li S, Ratliff SS, Roach A, Misquith A, Chan CL, Coppieters K, von Herrath M. Multicomponent Plasmid Protects Mice From Spontaneous Autoimmune Diabetes. Diabetes. 2021 Aug 13;71(1):157-69. doi: 10.2337/db21-0327. Online ahead of print.
- Individual participant dataSharing planned: Yes. Data will be available at the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) Central Repository
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robin Goland, MD study chair
Type 1 Diabetes TrialNet
Carla Greenbaum, MD study director
Type 1 Diabetes TrialNet
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NNC0361-0041 in people with Type I Diabetes, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: 16 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04279613, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2025.