Clinical trial NCT04812262: A Phase 1 Study of DD01 in Overweight/Obese Subjects With T2DM and NAFLD
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DD01 in Overweight/Obese Subjects With T2DM and NAFLD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Overweight and Obesity
Type2 Diabetes
NAFLD
Keywords: Liver Disease
Lead sponsor: Neuraly, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-23
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A - Cohorts A1, A2, A3, A4, A5, A6, A7 \& A8 Part B - Cohorts B2, B3, B4, B5, B6, B7 \& B8
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, first in human (FiH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to investigate the safety, tolerability, PK and PD of DD01 administered by subcutaneous (SC) injection in overweight/obese subjects with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD).

The study will be conducted in 2 Parts (Part A and B), with up to 8 cohorts included in each part (Part A; Cohorts A1 to A8 and Part B; Cohorts B2 to B8).

Detailed description: Part A (SAD):

In Part A, subjects will receive a single dose of study drug, and the safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM.

Part B (MAD):

In Part B, subjects will receive once-weekly doses of the study drug for 4 weeks, and the safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM and NAFLD.

Eligibility criteria: Part A Inclusion Criteria:

* Type 2 diabetes ≥ 12 months.
* Treatment with diet and exercise or metformin monotherapy on stable dose for 3 months prior to screening
* HbA1c ≤ 10%).
* Body Mass Index (BMI) ≥ 25 and ≤ 40.0 kg/m2

Part B Inclusion Criteria

* Type 2 diabetes ≥ 12 months.
* Treatment with diet and exercise or metformin monotherapy on stable dose for 3 months prior to screening
* HbA1c ≤ 10%
* BMI ≥ 30 kg/m2 and ≤ 40.0 kg/m2
* Waist circumference ≤ 57 inches
* Controlled attenuation parameter by FibroScan
* Liver fat fraction ≥ 10% by magnetic resonance imaging (MRI)

Part A Exclusion Criteria:

* History of type 1 diabetes mellitus (T1DM)
* History of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
* Uncontrolled hypertension
* Treatment with antihypertensive medication and statins not stable during the past 2 months prior to screening
* Treatment with thyroid hormones not stable during the past 3 months prior to screening
* History of any weight control treatment, including over-the-counter and herbal medication and supplements, or any medication with a labeled indication for weight loss or weight gain within 3 months prior to screening
* History of surgical treatment for obesity
* History of heart disease
* History of renal disease
* History or current diagnosis of acute or chronic pancreatitis or factors for pancreatitis, such as a history of cholelithiasis (without cholecystectomy) or alcohol abuse
* A history of or active chronic liver disease due to alcohol, auto-immune, HIV, HBV or active HCV-infection or NASH
* History of major depression, anxiety, suicidal behavior or attempts, or other psychiatric disorder requiring medical treatment
* Personal or family history of medullary thyroid carcinoma (MTC) or a genetic condition that predispose to MTC (i.e., multiple endocrine neoplasia type 2)
* Administration of Vaccines/Immunizations within 14 days prior to first dosing or if scheduled during the study. Vaccination for COVID-19 is allowed during the study if a washout period of 5 days after vaccine administration is followed before dosing.
* History of any major surgery within 6 months prior to screening
* Participation in any other clinical interventional study receiving active treatment within 30 days or 5 half-lives prior to screening, whichever is longer
* History of alcohol or illicit drug abuse including marijuana
* Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the investigational product

PART B Exclusion Criteria

* History of type 1 diabetes mellitus (T1DM)
* History of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator
* Uncontrolled hypertension (treatment with medications must be stable)
* History of any weight control treatment
* History of surgical treatment for obesity
* History of heart disease
* History of renal disease
* Subjects with a history or clinically significant active disease of the gastrointestinal, cardiovascular, hepatic, neurological, renal, pancreatic, immunological, dermatological, endocrine, genitourinary or hematological system.
* History or current diagnosis of acute or chronic pancreatitis
* History of major depression, anxiety, suicidal behavior or attempts, or other psychiatric disorder requiring medical treatment
* History of alcohol or illicit drug abuse including marijuana
* Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the investigational product
* Any history of clinically significant chronic liver disease

Primary outcomes:
measure: Number of participants with treatment-related adverse events and serious adverse events
timeFrame: Part A - 43 days
measure: Number of participants with treatment-related adverse events and serious adverse events (TEAEs)
timeFrame: Part B - 57 days
measure: Number of participants with clinically significant abnormalities in clinical laboratory values
timeFrame: Part A - 43 days
measure: Number of participants with clinically significant abnormalities in clinical laboratory values
timeFrame: Part B - 57 days
measure: Number of participants with clinically significant abnormalities in physical examinations
timeFrame: Part A - 43 days
measure: Number of participants with clinically significant abnormalities in physical examinations
timeFrame: Part B - 57 days
measure: Number of participants with clinically significant abnormalities in vital signs
timeFrame: Part A - 43 days
measure: Number of participants with clinically significant abnormalities in vital signs
timeFrame: Part B - 57 days
measure: Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM)
timeFrame: Part A - 43 days
measure: Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM)
timeFrame: Part B - 57 days
measure: Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)
timeFrame: Part A - 43 days
measure: Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)
timeFrame: Part B - 57 days
measure: Number of participants with clinically significant abnormalities in 12-lead ECGs
timeFrame: Part A - 43 days
measure: Number of participants with clinically significant abnormalities in 12-lead ECGs
timeFrame: Part B - 57 days
Secondary outcomes:
measure: Maximum observed blood/plasma concentration of DD01
timeFrame: Part A - 43 days
measure: Maximum observed blood/plasma concentration of DD01
timeFrame: Part B - 57 days
measure: Time of the maximum observed blood/plasma concentration of DD01
timeFrame: Part A - 43 days
measure: Time of the maximum observed blood/plasma concentration of DD01
timeFrame: Part B - 57 days
measure: Apparent blood/plasma terminal elimination half life of DD01
timeFrame: Part A - 43 days
measure: Apparent blood/plasma terminal elimination half life of DD01
timeFrame: Part B - 57 days
measure: Termination elimination rate constant of DD01
timeFrame: Part A - 43 days
measure: Termination elimination rate constant of DD01
timeFrame: Part B - 57 days
measure: Apparent total blood/plasma clearance of DD01
timeFrame: Part A - 43 days
measure: Apparent total blood/plasma clearance of DD01
timeFrame: Part B - 57 days
measure: Apparent volume of distribution of DD01
timeFrame: Part A - 43 days
measure: Apparent volume of distribution of DD01
timeFrame: Part B - 57 days
measure: Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration of DD01
timeFrame: Part A - 43 days
measure: Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration of DD01
timeFrame: Part B - 57 days
measure: Area under the blood/plasma concentration time curve from time zero to 144 hours postdose of DD01
timeFrame: Part A - 43 days
measure: Area under the blood/plasma concentration time curve from time zero to 144 hours postdose of DD01
timeFrame: Part B - 57 days
measure: Area under the blood/plasma concentration time curve from time zero to 216 hours postdose of DD01
timeFrame: Part A - 43 days
measure: Area under the blood/plasma concentration time curve from time zero to 216 hours postdose of DD01
timeFrame: Part B - 57 days
measure: Area under the blood/plasma concentration time curve from time zero to 168 hours postdose of DD01
timeFrame: Part B - 57 days
measure: Number of participants with antidrug antibodies (ADAs)
timeFrame: Part A - 43 days
measure: Number of participants with antidrug antibodies (ADAs)
timeFrame: Part B - 57 days
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Prosciento
state: California
city: Fort Myers
country: United States
facility: Southwest General Healthcare Center
state: Florida
city: Orlando
country: United States
facility: Combined Research Orlando
state: Florida
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
Study officials:
References: