CC100: Phase 1 Multiple-Dose Safety and Tolerability in Subjects With ALS (CC100B)

Protocol CC100B. CC100: Phase 1 Multiple-Dose Safety and Tolerability in Subjects With ALS

Approximately 21 subjects with amyotrophic lateral sclerosis (ALS) will be randomized (6 to 1) to receive by mouth seven morning doses of CC100 or placebo for 7 days. Subjects are required to stay in the Clinic for approximately 9 hours following the first and last dose. Subjects will also have a mid-week clinic visit and will be contacted by phone within 3 to 5 days after the last dose.

Funding Source - FDA OOPD

Study Overview

• Status: Unknown
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: CC100; Drug: Placebos

Detailed Description

Primary objective: to assess the safety and tolerability of multiple doses of orally administered CC100 in subjects with amyotrophic lateral sclerosis (ALS). Secondary objectives: to determine pharmacokinetics and pharmacodynamics of CC100 in plasma after single and after multiple doses; and to determine short-term effects of CC100 on potential blood-cell ALS biomarkers.

Study Design: Phase 1 double-blind, randomized, placebo-controlled multiple-dose of three CC100-dose cohorts. Approximately 18 subjects will receive CC100. Approximately 3 subjects will be randomized to placebo (across 3 cohorts). Periodic Assessment Committee safety reviews. Note: Participation will not exclude subjects from future CC100 studies Criteria for Evaluation: Safety Endpoints: Adverse events, blood chemistry, hematology, urinalysis, vital signs, 12-lead ECGs. Pharmacokinetic (PK)/Pharmacodynamic (PD): Plasma for CC100 concentrations (PK). Blood collected at baseline and after each subject's last dose will be assayed for potential biomarker(s). Stored specimens will be de-identified or combined for validating diagnostic tools/assays related to ALS. Statistical Methods: A minimum of 6 subjects per CC100 dose group and 3 placebo-dosed subjects (total across cohorts) are considered sufficient to evaluate initial safety and tolerability for the cohorts. Pharmacokinetic parameter estimates will be calculated by standard noncompartmental methods of analysis. Absolute bioavailability of administration will be estimated based on the total area under the time- concentration curve (AUC0-∞).

• Study Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University, IU Health Physicians Neurology
      • Contact: Sandra Guingrich, LPN, CCRC; Phone Number: 317-963-7382; Email: sguingri@iu.edu
      • Principal Investigator: Robert Pascuzzi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have definite or probable ALS with a forced vital capacity of >60% predicted.
• Men must practice a reliable method of birth control during study and for 2 weeks following study. Women must be non-fertile or post-menopausal.
• Riluzole is allowed if dose has been stable for at least 30 days. Other allowed medications: lipid-lowering drugs, anti-hypertensives, anti-depressants, oral medications for type II diabetes, estrogen replacement therapy, thyroid replacement therapy, antihistamines, antacids, nonsteroidal anti-inflammatory drugs (except indomethacin), histamine H2-receptor antagonists, proton-pump inhibitors, calcium supplements, topical eye medications, and topical antibiotics.

Exclusion Criteria:

• Greater than 250 pounds
• Have serious or unstable illnesses as determine by the investigator.
• Have current or a history of asthma or severe drug allergies or pollen allergy.
• Have had serious infectious disease affecting the brain within the preceding 5 years; or have existing evidence of serious infection.
• Have laboratory test values that are considered clinically significant as determined by the investigators.
• Have ECG abnormalities that are clinically significant.
• Have donated blood (a pint or more) or received an experimental drug within 30 days prior to dosing.
• Have a history of chronic alcohol or drug abuse within the past 2 years.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CC100 250 mg; CC100 250 mg once daily by mouth for 7 days	Drug: CC100; synthetic caffeic acid phenethylester; Other Names: synthetic caffeic acid phenethylester
Active Comparator: CC100 500 mg; CC100 500 mg once daily by mouth for 7 days	Drug: CC100; synthetic caffeic acid phenethylester; Other Names: synthetic caffeic acid phenethylester
Active Comparator: CC100 1000 mg; CC100 1000 mg once daily by mouth for 7 days	Drug: CC100; synthetic caffeic acid phenethylester; Other Names: synthetic caffeic acid phenethylester
Placebo Comparator: Placebo; Placebo once daily by mouth for 7 days	Drug: Placebos; Diluent; Other Names: Placebo oral liquid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability: Adverse events, safety labs, vital signs, and ECGs	Safety and tolerability assessed by group/dose measured by number of unsolicited adverse events (MedDRA), and changes in blood chemistry, hematology, urinalysis, vital signs, and 12-lead ECGs from baseline (prior to dosing).	From start of first dose to a minimum of 3 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK)--Peak plasma concentration (Cmax)	Cmax after first (single) and last (multiple) CC100 doses	0.5, 1, 2, 4, and 8 hours after first and last dose
Pharmacokinetics (PK)--Area under the plasma concentration versus time curve (AUC)	AUC after first (single) and last (multiple) CC100 doses	0.5, 1, 2, 4, and 8 hours after first and last dose
Pharmacokinetics (PK)--Half life (T 1/2)	Estimated half-life after first (single) and last (multiple) CC100 doses	0.5, 1, 2, 4, and 8 hours after first and last dose
Pharmacodynamics (PD)--Monocyte chemotactic protein 1 (MCP-1)	Short-term effects of CC100 on potential ALS inflammation biomarker MCP-1	Pretreatment and 8 hours post last dose
Pharmacodynamics (PD)--Excitotoxicity/oxidative stress biomarkers	Short-term effects of CC100 on potential ALS excitotoxicity/oxidative stress biomarkers: Heme oxygenase-1 (HMOX-1)/thioredoxin (TRX)/heat-shock protein 70 (HSP-70)	Pretreatment and 8 hours post last dose

Collaborators and Investigators

• Sponsor: Chemigen, LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2017
• Primary Completion (Anticipated): January 30, 2018
• Study Completion (Anticipated): March 30, 2018

Study Registration Dates

• First Submitted: February 3, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): August 3, 2017
• Last Update Submitted That Met QC Criteria: August 1, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Caffeic acid
• Other Study ID Numbers: CC100B; 1R01FD004790-01A2 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Single-site study

Drug and device information, study documents

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