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

Primary Purpose

Type 1 Diabetes Mellitus

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

MHS552

Placebo

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring type 1 diabetes mellitus, T1DM

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

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/exclusion criteria may apply

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part A: Cohort 1 - MHS552 low dose

Part A: Cohort 1, 2, 3 - Placebo

Part A: Cohort 2 - MHS552 medium dose

Part A: Cohort 3 - MHS552 high dose

Part B: MHS552

Part B: Placebo

Arm Description

Participants will receive MHS552 low dose once weekly subcutaneously for 4 weeks

Participants will receive placebo once weekly subcutaneously for 4 weeks

Participants will receive MHS552 medium dose once weekly subcutaneously for 4 weeks

Participants will receive MHS552 high dose once weekly subcutaneously for 4 weeks

Participants will MHS552 (dose to be determined) once weekly subcutaneously for 12 weeks

Participants will receive placebo once weekly subcutaneously for 12 weeks

Outcomes

Primary Outcome Measures

Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)

Numbers of participants with AEs and SAEs including vital signs, electrocardiograms (ECG) and laboratory results

Secondary Outcome Measures

Area Under Plasma Concentration-time Curve calculated to the end of a dosing interval (AUCtau) for MHS552

Characterize the AUCtau profile following multiple doses of MHS552

Maximum ObservBlood Concentrations (Cmax) for MHS552

Characterize the Cmax profile following multiple doses of MHS552

Time to Reach Maximum Blood Concentrations (Tmax) of MHS552

Characterize the Tmax profile following multiple doses of MHS552

Full Information

NCT ID

NCT05272059

First Posted

February 28, 2022

Last Updated

April 5, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05272059

Brief Title

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

Official Title

A Randomized, Investigator and Participant Blinded, Placebo Controlled, Multiple Ascending Dose, Two Part Design Study to Assess the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of MHS552 in Adults With Type 1 Diabetes Mellitus (T1DM)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor decision

Study Start Date

September 1, 2023 (Anticipated)

Primary Completion Date

April 14, 2025 (Anticipated)

Study Completion Date

April 14, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes Mellitus

Keywords

type 1 diabetes mellitus, T1DM

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A: Cohort 1 - MHS552 low dose

Arm Type

Experimental

Arm Description

Participants will receive MHS552 low dose once weekly subcutaneously for 4 weeks

Arm Title

Part A: Cohort 1, 2, 3 - Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive placebo once weekly subcutaneously for 4 weeks

Arm Title

Part A: Cohort 2 - MHS552 medium dose

Arm Type

Experimental

Arm Description

Participants will receive MHS552 medium dose once weekly subcutaneously for 4 weeks

Arm Title

Part A: Cohort 3 - MHS552 high dose

Arm Type

Experimental

Arm Description

Participants will receive MHS552 high dose once weekly subcutaneously for 4 weeks

Arm Title

Part B: MHS552

Arm Type

Experimental

Arm Description

Participants will MHS552 (dose to be determined) once weekly subcutaneously for 12 weeks

Arm Title

Part B: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive placebo once weekly subcutaneously for 12 weeks

Intervention Type

Drug

Intervention Name(s)

MHS552

Intervention Description

MHS552 will be administered once weekly as subcutaneous injection for 4 (Part A) or 12 weeks (Part B)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administered once weekly as subcutaneous injection for 4 (Part A) or 12 weeks (Part B)

Primary Outcome Measure Information:

Title

Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)

Description

Numbers of participants with AEs and SAEs including vital signs, electrocardiograms (ECG) and laboratory results

Time Frame

Part A: up to 12 weeks; Part B: up to 20 weeks

Secondary Outcome Measure Information:

Title

Area Under Plasma Concentration-time Curve calculated to the end of a dosing interval (AUCtau) for MHS552

Description

Characterize the AUCtau profile following multiple doses of MHS552

Time Frame

Part A: up to Day 78; Part B: up to Day 134

Title

Maximum ObservBlood Concentrations (Cmax) for MHS552

Description

Characterize the Cmax profile following multiple doses of MHS552

Time Frame

Part A: up to Day 78; Part B: up to Day 134

Title

Time to Reach Maximum Blood Concentrations (Tmax) of MHS552

Description

Characterize the Tmax profile following multiple doses of MHS552

Time Frame

Part A: up to Day 78; Part B: up to Day 134

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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/exclusion criteria may apply

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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