A Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease

NCT03998514 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CB-4211-001
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 4

Brief Summary

This is a 3 part, randomized, double blind, placebo controlled study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending subcutaneous (SC) doses of CB4211 in healthy non obese subjects and subjects with NAFLD.

Conditions

Nonalcoholic Fatty Liver Disease

Keywords

Fatty Liver Disease; Liver Disease; Fatty Liver; Nonalcoholic Liver

Outcome Measures

Primary Outcomes (6)

• Incidence and severity of adverse events (AEs)

  Number of participants with treatment-related adverse events and serious adverse events

  up to 8 weeks for Part A; up to 9 weeks for Part B; up to 12 weeks for Part C

• Clinical laboratory evaluations

  Number of participants with clinically significant abnormalities in clinical laboratory values

  7 days for Part A; 2 weeks for Part B; 5 weeks for Part C

• Vital Signs

  Number of participants with clinically significant abnormalities in vital signs

  7 days for Part A; 2 weeks for Part B; 5 weeks for Part C

• 12-lead ECG parameters

  Number of participants with clinically significant abnormalities in 12-lead ECGs

  7 days for Part A; 2 weeks for Part B; 5 weeks for Part C

• Physical examinations

  Number of participants with clinically significant abnormalities in physical examinations

  Time Frame: up to 8 weeks for Part A; up to 9 weeks for Part B; up to 12 weeks for Part C

• Injection-site assessments

  Number of participants with treatment-related injection site reactions

  up to 8 weeks for Part A; up to 9 weeks for Part B; up to 12 weeks for Part C

Secondary Outcomes (12)

• Area under the blood/plasma concentration time curve from time zero to infinity of CB4211

  24 hours for Part A, 7 days for Part B, 28 days for Part C

• Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration of CB4211

  24 hours for Part A, 7 days for Part B, 28 days for Part C

• Area under the blood/plasma concentration time curve from time zero to 24 hours postdose of CB4211

  24 hours for Part A, 7 days for Part B, 28 days for Part C

• Maximum observed blood/plasma concentration of CB4211

  24 hours for Part A, 7 days for Part B, 28 days for Part C

• Time of the maximum observed blood/plasma concentration of CB4211

  24 hours for Part A, 7 days for Part B, 28 days for Part C

Other Outcomes (4)

• Change from baseline in body weight

  28 days for Part C only

• Change from baseline in liver fat (as determined by magnetic resonance imaging-derived proton density fat fraction [MRI-PDFF])

  28 days for Part C only

• Proportion of subjects achieving various levels of liver fat reduction at end of treatment

  28 days for Part C

Study Arms (10)

Group A1 single ascending dose (SAD)

EXPERIMENTAL

CB4211 Dose 1 (N=6) Placebo (N=2) Subcutaneous injection

Drug: CB4211 Dose 1; Drug: Placebo

Group A2 SAD

EXPERIMENTAL

CB4211 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection

Drug: CB4211 Dose 2; Drug: Placebo

Group A3 SAD

EXPERIMENTAL

CB4211 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection

Drug: CB4211 Dose 3; Drug: Placebo

Group A4 SAD

EXPERIMENTAL

CB4211 Dose 4 (N=1) Placebo (N=1) Subcutaneous injection

Drug: CB4211 Dose 4; Drug: Placebo

Group A5 SAD

EXPERIMENTAL

CB4211 Dose 5 (N=6) Placebo (N=2) Subcutaneous injection

Drug: CB4211 Dose 5; Drug: Placebo

Group A6 SAD

EXPERIMENTAL

CB4211 Dose 6 (N=6) Placebo (N=2) Subcutaneous injection

Drug: CB4211 Dose 6; Drug: Placebo

Group B1 multiple ascending dose (MAD)

EXPERIMENTAL

CB4211 Dose to be determined (TBD) (N=6) Placebo (N=2) Subcutaneous injection once daily for 7 days

Drug: CB4211 Dose TBD; Drug: Placebo

Group B2 MAD

EXPERIMENTAL

CB4211 Dose TBD (N=6) Placebo (N=2) Subcutaneous injection once daily for 7 days

Drug: CB4211 Dose TBD; Drug: Placebo

Group B3 MAD

EXPERIMENTAL

CB4211 Dose TBD (N=6) Placebo (N=2) Subcutaneous injection once daily for 7 days

Drug: CB4211 Dose TBD; Drug: Placebo

Part C

EXPERIMENTAL

CB4211 Dose TBD (N=10) Placebo (N=10) Subcutaneous injection once daily for 28 days

Drug: CB4211 Dose TBD; Drug: Placebo

Interventions

CB4211 Dose 1 DRUG

Administered by subcutaneous injection

Group A1 single ascending dose (SAD)

CB4211 Dose 2 DRUG

Administered by subcutaneous injection

Group A2 SAD

CB4211 Dose 3 DRUG

Administered by subcutaneous injection

Group A3 SAD

CB4211 Dose 4 DRUG

Administered by subcutaneous injection

Group A4 SAD

CB4211 Dose 5 DRUG

Administered by subcutaneous injection

Group A5 SAD

CB4211 Dose 6 DRUG

Administered by subcutaneous injection

Group A6 SAD

CB4211 Dose TBD DRUG

Administered by subcutaneous injection

Group B1 multiple ascending dose (MAD); Group B2 MAD; Group B3 MAD; Part C

Placebo DRUG

Administered by subcutaneous injection

Group A1 single ascending dose (SAD); Group A2 SAD; Group A3 SAD; Group A4 SAD; Group A5 SAD; Group A6 SAD; Group B1 multiple ascending dose (MAD); Group B2 MAD; Group B3 MAD; Part C

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females of nonchildbearing potential, of any race, 18 to 60 years of age, inclusive, at Screening.
• Females of nonchildbearing potential are defined as permanently sterile (ie, due to hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) confirmed by history or postmenopausal (defined as at least 12 continuous months without menses and follicle-stimulating hormone (FSH) ≥40 milli-International unit (mIU)/L and without an alternative medical cause).
• Body mass index between 18.0 and 30.0 kg/m2 , inclusive, with a minimum body weight of 50.0 kg at Screening.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, Gilbert's syndrome\] is not acceptable) at Screening or Check-in as assessed by the Investigator (or designee).
• Males will agree to use contraception.
• Has maintained stable weight (by history) for at least 4 weeks prior to Screening.
• Agrees to the following:
• Not to initiate a weight-loss program from Screening until the Follow-up visit;
• To refrain from strenuous exercise from 7 days before Check-in until the Follow-up visit;
• To maintain consistent dietary habits and exercise routines for the duration of the study.
• Must have transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and total bilirubin within the normal range at Screening and Check-in. For other laboratory evaluations, the subject may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant.
• Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.

You may not qualify if:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
• Clinically significant ECG abnormalities or QT interval corrected for heart rate using Fridericia's method (QTcF) \>450 milliseconds for males and \>470 milliseconds for females at either Screening or Check-in, or any prior history of QT abnormality.
• Creatinine clearance of \<90 mL/min at Screening, determined using the Cockcroft-Gault (C-G) equation.
• History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• History of alcoholism or drug/chemical abuse within 2 years prior to Check-in.
• Alcohol consumption of \>21 units per week for males and \>14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
• Positive urine drug screen (confirmed by repeat) at Screening or positive alcohol breath or urine test result or positive urine drug screen at Check-in.
• Positive hepatitis panel and/or positive human immunodeficiency virus test. Subjects with serologic finding of immunity consistent with history of prior hepatitis B vaccination may be enrolled.
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing or have received a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to dosing.
• Use of prescription drugs, nonprescription drugs, dietary supplements including Vitamin E, herbal supplements, hormonal therapy/replacement, or CYP3A4 substrates, inducers and inhibitors within 14 days prior to the first dose of study drug unless, in the opinion of the Investigator and Sponsor's Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety.
• Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to the first dose of study medication, unless deemed acceptable by the Investigator (or designee).
• Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
• Receipt of blood products within 2 months prior to Check-in.

Sponsors & Collaborators

• CohBar, Inc.: lead

Study Sites (4)

ProScietno

Chula Vista, California, 91911, United States

Location

Covance Clinical Research Unit Inc.

Dallas, Texas, 75247, United States

Location

The Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Endeavor Clinical Trials, LLC

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Jiang J, Xu L, Yang L, Liu S, Wang Z. Mitochondrial-Derived Peptide MOTS-c Ameliorates Spared Nerve Injury-Induced Neuropathic Pain in Mice by Inhibiting Microglia Activation and Neuronal Oxidative Damage in the Spinal Cord via the AMPK Pathway. ACS Chem Neurosci. 2023 Jun 21;14(12):2362-2374. doi: 10.1021/acschemneuro.3c00140. Epub 2023 Jun 7.

  PMID: 37285113 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Diseases; Fatty Liver

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: randomized, double blind, placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a 3-part, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, PK, and PD of single- and multiple-ascending SC doses of CB4211 in healthy subjects and subjects with NAFLD. Study treatment (CB4211 or placebo) will be administered SC into the abdomen (and if needed, upper and lower thigh) as bolus injections.

Study Record Dates

• First Submitted: June 21, 2019
• First Posted: June 26, 2019
• Study Start: July 9, 2018
• Primary Completion: April 19, 2021
• Study Completion: April 19, 2021
• Last Updated: May 11, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)