Type 1 Diabetes Mellitus
Conditions
Keywords
type 1 diabetes mellitus, T1DM
Brief summary
The purpose of this two-part multiple ascending dose study is to evaluate the safety and tolerability of multiple doses of MHS552 in adults with type 1 diabetes mellitus. Participants will be treated for 4 or 12 weeks followed by an 8 week follow-up period
Detailed description
This is a Phase 1b, randomized, investigator and participant blinded, placebo controlled, multiple ascending dose (MAD) study in adults with type 1 diabetes mellitus (adults aged 18-45 years, inclusive, diagnosed with T1DM within 5 years at the time of screening). This MAD study will be conducted in two sequential parts, Part A and Part B. In Part A, after an screening period of up to 28 days, participants will be randomized (in a 3:1 ratio) to MHS552 or placebo administered subcutaneously (s.c.) weekly for four weeks of treatment. Part A will consist of up to 3 cohorts (low, medium, high dose), with approximately 4-8 participants completing each cohort (total of approximately 16 participants). Participants will be followed-up during 8 weeks post last dose. The total duration of study participation of Part A is approximately 106 Days. In Part B, after a screening period of up to 28 days, approximately 12 participants will be randomized (in a 2:1 ratio) to MHS552 or placebo administered s.c. weekly for 12 weeks of treatment (dose level 4). Participants will be followed-up during 8 weeks post last dose with End of Study (EoS) visit at Day 134. The total duration of study participation of Part B is approximately 162 Days.
Interventions
DRUGMHS552
MHS552 will be administered once weekly as subcutaneous injection for 4 (Part A) or 12 weeks (Part B)
DRUGPlacebo
Placebo will be administered once weekly as subcutaneous injection for 4 (Part A) or 12 weeks (Part B)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Adult men and women ages 18 to 45, inclusive, body weight between ≥40 to ≤150 kg, inclusive, with T1DM, a maximum of 5 years from T1DM diagnosis at screening. * Evidence of one or more T1DM autoantibody(ies) including glutamic acid decarboxylase (anti GAD), protein tyrosine, phosphatase-like protein (anti-IA-2); zinc transporter 8 (anti-ZnT8); islet cell (cytoplasmic) (anti-ICA) * Residual pancreatic β-cell function (fasting C-peptide \>100 pmol/L \[0.30 ng/mL\] or random C peptide \>200 pmol/L \[0.60 ng/mL\])
Exclusion criteria
* History of hypersensitivity to drugs of similar biological class, IL-2 protein analogues, or immunoglobulin (IgG1) proteins, hypersensitivity to any components of the study drug, or history of severe hypersensitivity reaction or anaphylaxis to biological agents, e.g. human monoclonal antibody. * Use of other investigational drugs or use of immunosuppressive agents at the time of enrollment, or within 5 half-lives of enrollment, or until the expected PD effect has returned to baseline, whichever is longer; or longer if required by local regulations. * Diabetes forms other than autoimmune type 1 such as maturity-onset diabetes of the young (MODY), latent autoimmune diabetes of the adult (LADA), acquired diabetes (secondary to medications or surgery), type 2 diabetes by judgement of the investigator. * Diabetic ketoacidosis within 2 weeks. * Polyglandular auto-immune disease, including but not limited to: Addison's disease, pernicious anemia, celiac sprue and psoriasis. Treated, stable Hashimoto's thyroiditis is not exclusionary. * History of capillary leak syndrome (CLS). * Ongoing, and up to 2 weeks prior to screening, initiation of medications or change in dose of medications that may affect glucose control (e.g, systemic steroids, thiazides, beta blockers). Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs) | Part A: up to 12 weeks; Part B: up to 20 weeks | Numbers of participants with AEs and SAEs including vital signs, electrocardiograms (ECG) and laboratory results |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Plasma Concentration-time Curve calculated to the end of a dosing interval (AUCtau) for MHS552 | Part A: up to Day 78; Part B: up to Day 134 | Characterize the AUCtau profile following multiple doses of MHS552 |
| Maximum ObservBlood Concentrations (Cmax) for MHS552 | Part A: up to Day 78; Part B: up to Day 134 | Characterize the Cmax profile following multiple doses of MHS552 |
| Time to Reach Maximum Blood Concentrations (Tmax) of MHS552 | Part A: up to Day 78; Part B: up to Day 134 | Characterize the Tmax profile following multiple doses of MHS552 |
Outcome results
None listed