A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041

NCT04279613 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: TN27 Immunoplasmid TherapyUC4DK117009
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 16

Brief 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.

Conditions

Type I Diabetes

Outcome Measures

Primary Outcomes (1)

• 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)

  16 Weeks

Secondary Outcomes (1)

• Change in the Area Under the Plasma C-peptide Concentration-time Curve Across the 2-hour Test Period.

  4-, 12-, 24- and 52-weeks from baseline

Study Arms (2)

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

Drug: NNC0361-0041

Placebo

PLACEBO COMPARATOR

Dosage form: Solution for injection Route of administration: Subcutaneous Dosing instructions: Once weekly on site

Other: Placebo

Interventions

NNC0361-0041 DRUG

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.

NNC0361-0041

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• Novo Nordisk A/S: collaborator

Study Sites (16)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Barbara Davis Center at University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Emory Children's Center

Atlanta, Georgia, 30329, United States

Location

Indiana University - Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Regents of the University of Minnesota

Minneapolis, Minnesota, 55466, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

The Naomi Berrie Diabetes Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt Eskind Diabetes Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Benaroya Research Institute

Seattle, Washington, 98101, United States

Location

Related Publications (2)

• Pagni 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:db210327. doi: 10.2337/db21-0327. Online ahead of print.

  PMID: 34957480 DERIVED

• Pagni 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.

  PMID: 34389610 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Dr. Kevan Herold
• Organization: Yale University

kevan.herold@yale.edu

203-785-6507

Study Officials

• Robin Goland, MD

  Type 1 Diabetes TrialNet

  STUDY CHAIR

• Carla Greenbaum, MD

  Type 1 Diabetes TrialNet

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: February 19, 2020
• First Posted: February 21, 2020
• Study Start: November 23, 2020
• Primary Completion: August 31, 2023
• Study Completion: April 24, 2024
• Last Updated: May 20, 2025
• Results First Posted: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (16)