Multiple Ascending Dose Study of MHS552 in Adults With Type 1 Diabetes Mellitus

Phase 1

Withdrawn

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: MHS552

• Registration Number: NCT05272059
• Lead Sponsor: Novartis Pharmaceuticals

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.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2022-02-28
• Study First Submitted QC: 2022-02-28
• Study First Posted: 2022-03-09
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-05
• Last Update Posted: 2023-04-07
• Study Start: 2023-09-01
• Primary Completion: 2025-04-14
• Study Completion: 2025-04-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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])

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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/exclusion criteria may apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part B: Placebo	Placebo	Participants will receive placebo once weekly subcutaneously for 12 weeks
Part A: Cohort 1, 2, 3 - Placebo	Placebo	Participants will receive placebo once weekly subcutaneously for 4 weeks
Part A: Cohort 3 - MHS552 high dose	MHS552	Participants will receive MHS552 high dose once weekly subcutaneously for 4 weeks
Part B: MHS552	MHS552	Participants will MHS552 (dose to be determined) once weekly subcutaneously for 12 weeks
Part A: Cohort 2 - MHS552 medium dose	MHS552	Participants will receive MHS552 medium dose once weekly subcutaneously for 4 weeks
Part A: Cohort 1 - MHS552 low dose	MHS552	Participants will receive MHS552 low dose once weekly subcutaneously for 4 weeks

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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