Cadisegliatin as Adjunctive Therapy in Type 1 Diabetes (CATT1)

Cadisegliatin as Adjunctive Therapy in Type 1 Diabetes: A 52-Week Double-Blind, Randomized, Placebo-Controlled Phase 3 Study

This is a Phase 3 trial of cadisegliatin in participants with Type 1 Diabetes Mellitus.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Placebo; Drug: Cadisegliatin 800 mg QD; Drug: Cadisegliatin 800 mg BID

Detailed Description

Study TTP399-302 is a 52-week, Phase 3 trial designed to measure the relative efficacy of treatment with cadisegliatin to reduce the incidence of Level 2 or Level 3 hypoglycemia in participants with Type 1 Diabetes Mellitus compared to placebo over 26 weeks of continuous therapy.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jennifer Freeman, Ph.D.; Phone Number: (336) 888-0435; Email: clinicaltrials@vtvtherapeutics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals ≥18 years
• Diagnosed T1DM with a minimum of 5 years since diagnosis
• Has had at least 1 hypoglycemic event of Level 2 (glucose level <54 mg/dL or <3 mmol/L, [CGM or SMBG confirmed]) or Level 3 (defined as a severe hypoglycemia with altered mental state and/or physical status requiring assistance) in the last 2 months prior to Screening
• HbA1c value of <9.5% at Screening
• Is currently on CSII (closed-loop systems are prohibited) or is on MDI for at least 6 months prior to the Screening Visit and is willing to stay on same type of insulin treatment and the current mode of insulin administration (CSII or MDI injection treatments) for the duration of the study
• Must have used a CGM device for at least 3 consecutive months prior to Screening

Exclusion Criteria:

• Has T2DM, monogenic diabetes, maturity-onset diabetes of the young, other unusual or rare forms of diabetes mellitus, or diabetes resulting from a secondary disease
• Has been hospitalized for DKA within 3 months prior to Screening
• Has uncontrolled hypothyroidism or hyperthyroidism
• History of eating disorder within the last 2 years such as anorexia, bulimia, diabulimia or neglecting to give insulin to manipulate weight
• Has an active or untreated malignancy, or has been in remission from malignancy for ≤5 years except well-treated basal cell or squamous cell skin cancer or cervical cancer in situ
• Has used any of the following medications within the specified time periods - any non- insulin anti-diabetic therapies, e.g., sodium glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, metformin, sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, or pramlintide within 90 days prior to the Screening or weight loss medications within 30 days prior to the Screening
• Has used a hybrid closed-loop system (e.g., Medtronic 670G, Omnipod 5, or Tandem X2 with control IQ) or Do-It-Yourself looping within the last 1 month prior to the Screening Visit, and agrees to not start hybrid closed-loop systems or Do-It-Yourself looping during the study.
• Has an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 utilizing the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at Screening
• Has persistent, uncontrolled hypertension prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadisegliatin: 52 Week Double Blind Treatment Period; The main study uses a randomized, double-blind, placebo-controlled design with parallel assignment among 3 treatment arms. The trial begins with a screening period of up to 14 days, followed by a 28-day device training and insulin adjustment period leading into a 28-day baseline period before entering the 52-week treatment period.	Drug: Cadisegliatin 800 mg QD; Cadisegliatin is an orally bioavailable small-molecule glucokinase activator.; Other Names: TTP399; Drug: Cadisegliatin 800 mg BID; Cadisegliatin is an orally bioavailable small-molecule glucokinase activator.; Other Names: TTP399
Placebo Comparator: Placebo: 52 Week Double Blind Treatment Period; Matching placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in incidence of Level 2 or Level 3 hypoglycemia	Number of events of Level 2 or Level 3 hypoglycemia in participants on cadisegliatin vs placebo.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the change in HbA1c	Change from baseline in HbA1c in participants on cadisegliatin vs placebo.	26 weeks
To assess the effects of treatment on CGM-based metrics for glycemic control	To evaluate the change from baseline for time in, above or below target range of participants on cadisegliatin vs placebo	26 weeks
To assess the effects of treatment on the incidence of diabetic ketoacidosis	Number of events of diabetic ketoacidosis participants on cadisegliatin vs placebo	26 weeks
To assess the effects of treatment on insulin dosing	Change from baseline in basal, bolus and total insulin dosing	26 weeks
To assess the effects of treatment on body weight	Change from baseline in mean body weight	26 weeks
To assess the incidence of adverse events	Evaluation and comparison of the number of adverse events with cadisegliatin vs placebo during the study	26 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in incidence of Level 2 or Level 3 hypoglycemia	Number of events of Level 2 or Level 3 hypoglycemia in participants on cadisegliatin vs placebo.	52 weeks
To assess the change in HbA1c	Change from baseline in HbA1c in participants on cadisegliatin vs placebo	52 weeks
To assess the effects of treatment on CGM-based metrics for glycemic control	To evaluate the change from baseline for time in, above or below target range of participants on cadisegliatin vs placebo	52 weeks
To assess the incidence of adverse events	Evaluation and comparison of the number of adverse events with cadisegliatin vs placebo during the study	52 weeks
To assess the effects of treatment on the incidence of diabetic ketoacidosis	Percentage of participants with incidence of diabetic ketoacidosis on cadisegliatin vs placebo	52 weeks
To assess the effects of treatment on insulin dosing	Change from baseline in basal, bolus and total insulin dosing	52 weeks
To assess the effects of treatment on body weight	Change from baseline in mean body weight	52 weeks
High sensitivity C-reactive protein	Change from baseline of biomarkers	26 and 52 weeks
N-terminal pro brain [or B-type] natriuretic peptide	Change from baseline of biomarkers	26 and 52 weeks
Urinary albumin excretion ratio	Change from baseline of biomarkers	26 and 52 weeks
Estimated glomerular filtration rate	Change from baseline of biomarkers	26 and 52 weeks
8-item Diabetes Distress Scale (participant and partner or family member)	Change from baseline in PRO scores to assess the burden of hypoglycemia	26 and 52 weeks
Hypoglycemia Confidence Scale for participant and partner or family member	Change from baseline in PRO scores to assess the burden of hypoglycemia	26 and 52 weeks
11-item/Short Form Hypoglycemia Fear Scale	Change from baseline in PRO scores to assess the burden of hypoglycemia	26 and 52 weeks
Gold hypoglycemia awareness score	Change from baseline in patient reported outcomes scores to assess the burden of hypoglycemia. Scale from 1 (always aware) to 7 (never aware).	26 and 52 weeks
Item 7 of Clarke hypoglycemia awareness scale	Change from baseline in patient reported outcomes scores to assess the burden of hypoglycemia. Scale from less than 40 mg/dL to 79mg/dL.	26 and 52 weeks
Snyder's 1-item quality of sleep questionnaire	Change from baseline in patient reported outcomes scores to assess the burden of hypoglycemia. Scale from 0 (terrible) to 10 (excellent).	26 and 52 weeks
World Health Organization-5 Well-Being Index	Change from baseline in patient reported outcomes scores to assess the burden of hypoglycemia. Ranges from not confident to very confident.	26 and 52 weeks

Collaborators and Investigators

• Sponsor: vTv Therapeutics
• Investigators: Study Director: Thomas Strack, MD, vTv Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: TTP399-302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No