NCT02222714

Brief Summary

The purpose of this study was to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of multiple ascending intravenous doses of 3K3A-APC, a Recombinant Variant of Human activated protein C (APC), in in the treatment of acute ischemic stroke following treatment with recombinant tissue plasminogen activator (tPA), mechanical thrombectomy or both.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
110

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Oct 2014

Geographic Reach
1 country

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 18, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 21, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

October 1, 2014

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 18, 2017

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 29, 2017

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

November 8, 2018

Completed
Last Updated

November 8, 2018

Status Verified

October 1, 2018

Enrollment Period

2.5 years

First QC Date

August 18, 2014

Results QC Date

July 27, 2018

Last Update Submit

October 10, 2018

Conditions

Ischemic Stroke

Keywords

ischemic strokestrokeAPC3K3A3K3A-APCactivated protein CRHAPSODY

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Adverse Events That Meet Dose-limiting Toxicity (DLT) Criteria Specified in Protocol

    Specific AEs in the study were defined in the protocol to be dose-limiting toxicity events. Any given patient was adjudicated in a binary way to either have had a DLT or not to have had a DLT.

    48-hours following last dose

Secondary Outcomes (7)

  • Number of Participants With a Presence of Measurable Bleeds in the Brain (Hemorrhage and Microbleeds) as Determined by 1.5T MRI

    Day 30

  • PK of 3K3A-APC by Compartmental Analysis (Clearance)

    Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI

  • PK of 3K3A-APC by Compartmental Analysis (Volume of Distribution)

    Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI

  • PK of 3K3A-APC by Compartmental Analysis (Cmax)

    Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI

  • PK of 3K3A-APC by Compartmental Analysis (AUC[0-inf])

    Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI

  • +2 more secondary outcomes

Study Arms (5)

120 µg/kg of 3K3A-APC

ACTIVE COMPARATOR

3K3A-APC, q12h for up to 5 doses

Biological: 3K3A-APC

240 µg/kg of 3K3A-APC

ACTIVE COMPARATOR

3K3A-APC, q12h for up to 5 doses

Biological: 3K3A-APC

360 µg/kg of 3K3A-APC

ACTIVE COMPARATOR

3K3A-APC, q12h for up to 5 doses

Biological: 3K3A-APC

540 µg/kg of 3K3A-APC

ACTIVE COMPARATOR

3K3A-APC, q12h for up to 5 doses

Biological: 3K3A-APC

Placebo

PLACEBO COMPARATOR

Matching placebo, q12h for up to 5 doses

Drug: Placebo

Interventions

3K3A-APCBIOLOGICAL

3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Also known as: 3K3A-Activated Protein C
120 µg/kg of 3K3A-APC240 µg/kg of 3K3A-APC360 µg/kg of 3K3A-APC540 µg/kg of 3K3A-APC
PlaceboDRUG

Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion

Also known as: Matching Placebo
Placebo

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Acute ischemic stroke
  • Able to receive IV tPA, mechanical thrombectomy or both
  • National Institutes of Health Stroke Scale (NIHSS) score of ≥ 5
  • Signed informed consent
  • Mechanical thrombectomy subjects only: onset time to arterial puncture time \< 6 hours

You may not qualify if:

  • History of stroke or penetrating head injury within 90 days prior to enrollment
  • History of previous or current diagnosis of intracranial hemorrhage that represents a potential for re-hemorrhage if subjected to thrombolytic therapy or mechanical thrombectomy
  • Moyamoya disease, cerebral arterio-venous malformation (AVM), known unsecured aneurysm requiring intervention during the acute study period
  • Presence of other neurological or non-neurological co-morbidities that may lead, independently of the current stroke, to further deterioration in the subject's neurological status during the trial period
  • Presence of premorbid neurological deficits and functional limitations assessed by a retrospective Modified Rankin Scale (mRS) score of ≥ 2
  • Mechanical thrombectomy subjects only: baseline non-contrast CT scan revealing a large core occlusion as defined by local protocol
  • Prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT)
  • Severe hypertension or hypotension
  • Glomerular filtration rate (GFR) \<35 mL/min
  • Blood glucose concentration \< 50 mg/dL
  • Prior exposure to any exogenous form of APC

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Stroke Center

Los Angeles, California, 90048, United States

Location

Stroke Center

Chicago, Illinois, 60611, United States

Location

Stroke Center

Kansas City, Kansas, 66160, United States

Location

Stroke Center

Boston, Massachusetts, 02114, United States

Location

Stroke Center

St Louis, Missouri, 63110, United States

Location

Stroke Center

Buffalo, New York, 14209, United States

Location

Stroke Center

New York, New York, 10032, United States

Location

Stroke Center

Rochester, New York, 14642, United States

Location

Stroke Center

Cincinnati, Ohio, 45208, United States

Location

Stroke Center

Columbus, Ohio, 43210, United States

Location

Stroke Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Stroke Center

Nashville, Tennessee, 37232, United States

Location

Stroke Center

Dallas, Texas, 75390, United States

Location

Stroke Center

Salt Lake City, Utah, 84132, United States

Location

Stroke Center

Charlottesville, Virginia, 22904, United States

Location

Related Publications (3)

  • Lyden P, Levy H, Weymer S, Pryor K, Kramer W, Griffin JH, Davis TP, Zlokovic B. Phase 1 safety, tolerability and pharmacokinetics of 3K3A-APC in healthy adult volunteers. Curr Pharm Des. 2013;19(42):7479-85. doi: 10.2174/1381612819666131230131454.

    PMID: 24372304BACKGROUND

  • Lyden P, Pryor KE, Coffey CS, Cudkowicz M, Conwit R, Jadhav A, Sawyer RN Jr, Claassen J, Adeoye O, Song S, Hannon P, Rost NS, Hinduja A, Torbey M, Lee JM, Benesch C, Rippee M, Rymer M, Froehler MT, Clarke Haley E, Johnson M, Yankey J, Magee K, Qidwai J, Levy H, Mark Haacke E, Fawaz M, Davis TP, Toga AW, Griffin JH, Zlokovic BV; NeuroNEXT Clinical Trials Network NN104 Investigators. Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke. Ann Neurol. 2019 Jan;85(1):125-136. doi: 10.1002/ana.25383. Epub 2019 Jan 7.

    PMID: 30450637DERIVED

  • Lyden P, Weymer S, Coffey C, Cudkowicz M, Berg S, O'Brien S, Fisher M, Haley EC, Khatri P, Saver J, Levine S, Levy H, Rymer M, Wechsler L, Jadhav A, McNeil E, Waddy S, Pryor K. Selecting Patients for Intra-Arterial Therapy in the Context of a Clinical Trial for Neuroprotection. Stroke. 2016 Dec;47(12):2979-2985. doi: 10.1161/STROKEAHA.116.013881. Epub 2016 Nov 1.

    PMID: 27803392DERIVED

MeSH Terms

Conditions

Ischemic StrokeStroke

Interventions

3K3A-APC protein

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Limitations and Caveats

The study was designed and powered for evaluating DLTs and identifying a maximum tolerated dose, not for efficacy endpoints.

Results Point of Contact

Title
Patrick Lyden, MD, FAAN, FAHA
Organization
Cedars-Sinai Medical Center
Patrick.Lyden@cshs.org
(310) 423-5166

Study Officials

  • Patrick D. Lyden, MD

    Cedars-Sinai Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 18, 2014

First Posted

August 21, 2014

Study Start

October 1, 2014

Primary Completion

April 18, 2017

Study Completion

June 29, 2017

Last Updated

November 8, 2018

Results First Posted

November 8, 2018

Record last verified: 2018-10

Locations

US(15)