Status:

COMPLETED

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

Lead Sponsor:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborating Sponsors:

Novo Nordisk A/S

Conditions:

Type I Diabetes

Eligibility:

All Genders

18-45 years

Phase:

PHASE1

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 tolerab...

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...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

November 23 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

April 24 2024

Estimated Enrollment :

47 Patients enrolled

Trial Details

Trial ID

NCT04279613

Start Date

November 23 2020

End Date

April 24 2024

Last Update

May 20 2025

Active Locations (16)

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Page 1 of 4 (16 locations)

1

Children's Hospital of Orange County

Orange, California, United States, 92868

2

University of California - San Francisco

San Francisco, California, United States, 94143

3

Stanford University

Stanford, California, United States, 94305

4

Barbara Davis Center at University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States, 80045