Study to Assess the Efficacy and Safety of VX-210 in Subjects With Acute Traumatic Cervical Spinal Cord Injury

• ClinicalTrials.gov Identifier: NCT02669849
• Recruitment Status: Terminated
• First Posted: February 1, 2016
• Results First Posted: January 22, 2020
• Last Update Posted: January 22, 2020
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Study Description

Brief Summary:

The purpose of this study is to determine the efficacy and safety of VX-210 in subjects with Acute Traumatic Cervical Spinal Cord Injury. Secondary objectives include the specific evaluation of the effects of VX-210 on neurological recovery and daily function after spinal cord injury.

Condition or disease	Intervention/treatment	Phase
Cervical Spinal Cord Injury	Drug: VX-210; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2b/3, Double-blind, Randomized, Placebo Controlled, Multicenter Study to Assess the Efficacy and Safety of VX-210 in Subjects With Acute Traumatic Cervical Spinal Cord Injury
• Actual Study Start Date: July 2016
• Actual Primary Completion Date: November 2018
• Actual Study Completion Date: November 2018

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: VX-210	Drug: VX-210

Outcome Measures

Primary Outcome Measures :

1. Change in Upper Extremity Motor Score (UEMS) [ Time Frame: From baseline at 6 months post-treatment ]
   UEMS focuses selectively on the hand and arm control most relevant to individuals with a cervical spinal cord injury. UEMS ranges from 0 to 50, where a higher score indicates a better movement of hand and arm.

Secondary Outcome Measures :

1. Spinal Cord Independence Measure (SCIM) III Self-Care Subscore [ Time Frame: At 6 months post-treatment ]
   SCIM self-care subscore measures self-care abilities (feeding, dressing, grooming, bathing), respiration and sphincter management and mobility. The score ranges from 0-20, where a higher score represents a better outcome.
2. Capabilities of Upper Extremity Test (CUE-T) Score [ Time Frame: At 6 months post-treatment ]
   CUE-T measures a participant's ability to perform specific functional movements/tasks with the arms and hands (for example: grasping a pencil, pushing or lifting a weight). CUE-T score ranges from 0-128, where a higher score indicates an improvement in participant's ability.
3. Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) Quantitative Prehension Score [ Time Frame: At 6 months post-treatment ]
   GRASSP measures participant's ability to perform specific functional tasks with the arms, hands, and fingers. GRASSP quantitative prehension score ranges from 0-60, where a higher score indicates a better performance.
4. Percentage of American Spinal Injury Association Impairment Scale (AIS) Grade Responders [ Time Frame: At 6 months post-treatment ]
   AIS ranks impairment according to body-wide motor/sensory results: Grade A: Complete (no sensory or motor function is preserved in the sacral segments S4 to 5); Grade B: Sensory Incomplete (sensory but not motor function is preserved below the neurological level and includes the sacral segments S4 to 5); Grade C: Motor Incomplete (motor function is preserved at the most caudal sacral segments); Grade D: Motor Incomplete (motor incomplete status as defined above, with at least half or more of key muscle functions below the single neurological level of injury having a muscle grade >=3; Grade E: Normal (sensation and motor function as tested are graded as normal in all segments). An AIS responder was defined as a subject with improvement by ≥2 AIS grades (i.e., baseline AIS Grade A changed to Grade C, D, or E; baseline AIS Grade B changed to D or E at 6 months after treatment).
5. Percentage of Motor Level Responders [ Time Frame: At 6 months post-treatment ]
   The motor level score for the right or left side assesses contraction strength of 10 key muscles in the upper and lower extremities on each side of the body; each muscle receives a score from 0 (total paralysis) to 5 ([normal] active movement). A motor level responder was defined as a subject with improvement by ≥2 motor levels on either side of the body (i.e., baseline level C4 changed to C6, C7, C8 on the left; or baseline level C5 changed to C7, C8 on the right).
6. Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-210 [ Time Frame: up to 53 hours post-treatment ]
7. Maximum Observed Plasma Concentration (Cmax) of VX-210 [ Time Frame: up to 53 hours post-treatment ]
8. Area Under Plasma Concentration Time Curve (AUC) of VX-210 [ Time Frame: up to 53 hours post-treatment ]

Eligibility Criteria

• Ages Eligible for Study: 14 Years to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Acute traumatic cervical SCI, motor level of C4, C5, C6, or C7 on each side:

  • Screening UEMS score must be ≤16 points on each side.
  • AIS A subjects with a C4 motor level on both sides must have at least 1 point of motor activity between C5 and T1 on at least 1 side.
  • AIS B subjects with a C4 motor level on both sides must have at least 1 point of motor activity between C5 and C7 on at least 1 side.
• American Spinal Injury Association Impairment Scale (AIS) grade A or AIS grade B.
• Scheduled and planned to undergo a spinal decompression/stabilization surgery that commences within 72 hours after the initial injury.
• Computed tomography (CT) scan or magnetic resonance imaging (MRI) is consistent with the subject's neurological deficit.

Exclusion Criteria:

• Participation in any other clinical study for acute SCI without approval by the sponsor.
• Inability to undergo decompression/stabilization surgery that commences within 72 hours after injury.
• One or more upper extremity muscle groups untestable during screening ISNCSCI examination.
• Acute SCI from gunshot or penetrating/stab wound; non-traumatic SCI (e.g., transverse myelitis, acute disc herniation); brachial plexus injury; complete spinal cord transection; or multifocal SCI.
• Females who are breastfeeding or have a positive serum pregnancy test.
• Body mass index (BMI) of ≥40 kg/m^2 at screening.
• History of an adverse reaction to a fibrin sealant or its components.
• Unconsciousness or other mental impairment that precludes reliable International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) examination.
• Known immunodeficiency, including human immunodeficiency virus, or use of immunosuppressive or cancer chemotherapeutic drugs.
• Any significant medical or psychiatric comorbidities that would significantly increase the risk of study enrollment and/or significantly interfere with study outcomes or assessments, in the judgment of the investigator.

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, Alabama

Birmingham, Alabama, United States

United States, Arizona

Tucson, Arizona, United States

United States, California

Fresno, California, United States

Orange, California, United States

Sacramento, California, United States

United States, Florida

Jacksonville, Florida, United States

Tampa, Florida, United States

United States, Georgia

Atlanta, Georgia, United States

Savannah, Georgia, United States

United States, Iowa

Iowa City, Iowa, United States

United States, Kentucky

Louisville, Kentucky, United States

United States, Maryland

Baltimore, Maryland, United States

United States, Massachusetts

Boston, Massachusetts, United States

United States, Michigan

Ann Arbor, Michigan, United States

United States, Minnesota

Minneapolis, Minnesota, United States

United States, Mississippi

Jackson, Mississippi, United States

United States, Missouri

Saint Louis, Missouri, United States

United States, New Mexico

Albuquerque, New Mexico, United States

United States, Ohio

Columbus, Ohio, United States

Toledo, Ohio, United States

United States, Oklahoma

Oklahoma City, Oklahoma, United States

United States, Pennsylvania

Hershey, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

United States, Rhode Island

Providence, Rhode Island, United States

United States, Texas

Austin, Texas, United States

Dallas, Texas, United States

San Antonio, Texas, United States

United States, Utah

Salt Lake City, Utah, United States

United States, Virginia

Falls Church, Virginia, United States

Richmond, Virginia, United States

Roanoke, Virginia, United States

United States, Washington

Seattle, Washington, United States

Canada, British Colombia

Vancouver, British Colombia, Canada

Canada, Nova Scotia

Halifax, Nova Scotia, Canada

Canada, Ontario

Toronto, Ontario, Canada

Canada, Quebec

Montreal, Quebec, Canada

Québec, Quebec, Canada

Canada

Saskatoon, Canada

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:

Study Protocol  [PDF] April 14, 2017

Statistical Analysis Plan  [PDF] January 15, 2019

More Information

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT02669849
• Other Study ID Numbers: VX15-210-101
• First Posted: February 1, 2016
• Results First Posted: January 22, 2020
• Last Update Posted: January 22, 2020
• Last Verified: January 2020

Additional relevant MeSH terms:

Spinal Cord Injuries; Wounds and Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System