A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

The study will generate data on safety, tolerability and pharmacokinetics after multiple daily doses of CK-2017357 in patients with ALS. Patients will be randomized into one of four different treatment groups, receiving daily oral doses of either placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Placebo (Part A); Drug: Riluzole 50 MG (Part B); Drug: Placebo (Part B); Drug: CK-2017357 (Part A); Drug: CK-2017357 (Part A); Drug: CK-2017357 (Part A); Drug: CK-2017357 (Part B); Drug: CK-2017357 (Part B); Drug: CK-2017357 (Part B)

Detailed Description

In Part A, approximately 24 patients will be randomized to one of four different treatment groups. After a 7-day washout of riluzole, patients in each treatment group will receive daily oral doses of placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days. Patients will take daily doses of CK-2017357 or placebo (Day 1 through Day 14) and will return to the study site on Day 2, Day 8 and Day 15. All patients will return for a follow-up visit 7 days (± 2 days) after their last dose.

In Part B, approximately additional 24 patients will be randomized to one of four different treatment groups as in Part A. Patients in Part B will be required to decrease their riluzole dose to 50 mg once a day (QD) for 7 days prior to randomization. After this 7 day period, patients will take riluzole at 50 mg QD concurrently with their morning dose of blinded study drug.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Florida
  • Kansas
    • Kansas City, Kansas, United States, 06053
      • University of Kansas
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Neuromuscular ALS-MND Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Drexel University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Able to comprehend and willing to sign an Informed Consent Form (ICF)
2. Males or females 18 years of age or older
3. A diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria)
4. Maximum voluntary grip strength in at least one hand between 10 & 40 pounds (females) and 10 & 60 pounds (males)
5. Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
6. Able to swallow tablets with water
7. Willing and able to remain off riluzole for 4 weeks (Part A only)
8. Currently taking and tolerating a stable dose of 50 mg BID riluzole (Part B only)
9. Willing and able to reduce daily dose of riluzole to 50 mg for 4 weeks (Part B only)
10. Willing and able to refrain from caffeine-containing products during study participation
11. Willing and able to remain off warfarin and theophylline-containing medications during study participation
12. Has a caregiver who is capable of observing and reporting patient status, and also assisting in the proper use of nocturnal oximetry equipment
13. Able to perform pulmonary function tests

Key Exclusion Criteria:

1. Life expectancy <3 months
2. Participation in any trial in which receipt of investigational study drug occurred within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
3. Any prior treatment with CK-2017357
4. Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Matching Placebo	Drug: Placebo (Part A); Placebo tablets once daily for 14 days (Part A); Drug: Riluzole 50 MG (Part B); One 50 mg tablet once daily for 14 days (Part B); Drug: Placebo (Part B); Placebo tablets once daily for 14 days (Part B)
EXPERIMENTAL: Active Drug Low Dose (CK-2017357 125 mg)	Drug: Placebo (Part A); Placebo tablets once daily for 14 days (Part A); Drug: Riluzole 50 MG (Part B); One 50 mg tablet once daily for 14 days (Part B); Drug: Placebo (Part B); Placebo tablets once daily for 14 days (Part B); Drug: CK-2017357 (Part A); One 125 mg CK-2017357 tablet once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part A); Two 125 mg CK-2017357 tablets once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part A); Three 125 mg CK-2017357 tablets once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); One 125 mg tablet once daily for 14 days (Part B); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); Two 125 mg tablets once daily for 14 days (Part B); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); Three 125 mg tablets once daily for 14 days (Part B); Other Names: tirasemtiv
EXPERIMENTAL: Active Drug Mid Dose (CK-2017357 250 mg)	Drug: Placebo (Part A); Placebo tablets once daily for 14 days (Part A); Drug: Riluzole 50 MG (Part B); One 50 mg tablet once daily for 14 days (Part B); Drug: Placebo (Part B); Placebo tablets once daily for 14 days (Part B); Drug: CK-2017357 (Part A); One 125 mg CK-2017357 tablet once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part A); Two 125 mg CK-2017357 tablets once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part A); Three 125 mg CK-2017357 tablets once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); One 125 mg tablet once daily for 14 days (Part B); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); Two 125 mg tablets once daily for 14 days (Part B); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); Three 125 mg tablets once daily for 14 days (Part B); Other Names: tirasemtiv
EXPERIMENTAL: Active Drug High Dose (CK-2017357 375 mg)	Drug: Riluzole 50 MG (Part B); One 50 mg tablet once daily for 14 days (Part B); Drug: CK-2017357 (Part A); One 125 mg CK-2017357 tablet once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part A); Two 125 mg CK-2017357 tablets once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part A); Three 125 mg CK-2017357 tablets once daily for 14 days (Part A); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); One 125 mg tablet once daily for 14 days (Part B); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); Two 125 mg tablets once daily for 14 days (Part B); Other Names: tirasemtiv; Drug: CK-2017357 (Part B); Three 125 mg tablets once daily for 14 days (Part B); Other Names: tirasemtiv

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Safety and tolerability of CK-2017357 after multiple oral doses to steady state in patients with ALS	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)	An instrument for evaluating the functional status of patients with ALS. Minimum score is 0 and maximum score is 40. The higher the score the more function is retained.	21 days
Measurement of Grip Strength and Handgrip Fatigue	Measured using the DynEx Electronic Hand Dynamometer. Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction. Handgrip fatigue is then measured. Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds.	21 days
Measurement of muscle strength	Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups.	21 days
Measurement of Slow Vital Capacity (SVC)	SVC will be measured using the ndd EasyOne Spirometer System at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit	21 days
Measurement of Sniff Nasal Inspiratory Pressure (SNIP)	SNIP will be measured using the Micro Medical Respiratory Pressure Meter (MicroRPM) at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit	21 days
Measurement of Maximum Voluntary Ventilation (MVV)	MVV will be measured using the EasyOne Spirometer System at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit	21 days
Patient global assessment	Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt at pre-dose on Day 1	15 days
Investigator global assessment	Investigator will assess whether the patient appears the same, better or worse as compared to the patient's status at pre-dose on Day 1.	15 days

Collaborators and Investigators

• Sponsor: Cytokinetics

Publications and helpful links

General Publications

• Shefner JM, Watson ML, Meng L, Wolff AA; Neals/Cytokinetics STUDY Team. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):574-81. doi: 10.3109/21678421.2013.822517. Epub 2013 Aug 19.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: June 20, 2011
• First Submitted That Met QC Criteria: June 21, 2011
• First Posted (ESTIMATE): June 22, 2011

Study Record Updates

• Last Update Posted (ACTUAL): May 7, 2019
• Last Update Submitted That Met QC Criteria: May 2, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neuroprotective Agents; Protective Agents; Anticonvulsants; Riluzole
• Other Study ID Numbers: CY 4024