Phase III Efficacy and Safety Study of AB103 in the Treatment of Patients With Necrotizing Soft Tissue Infections
Status: | Recruiting |
---|---|
Conditions: | Skin and Soft Tissue Infections, Infectious Disease, Infectious Disease |
Therapuetic Areas: | Dermatology / Plastic Surgery, Immunology / Infectious Diseases |
Healthy: | No |
Age Range: | 12 - Any |
Updated: | 3/10/2019 |
Start Date: | September 2015 |
End Date: | December 2019 |
Contact: | Wayne M Dankner, MD |
Email: | wayned@atoxbio.com |
Phone: | 919-219-6377 |
Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Study of AB103 as Compared to Placebo in Patients With Necrotizing Soft Tissue Infections. ACCUTE (AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections)
The purpose of this study is to determine whether AB103 is safe and effective in the
treatment of patients with necrotizing soft tissue infections receiving standard of care
therapy.
treatment of patients with necrotizing soft tissue infections receiving standard of care
therapy.
The primary hypothesis of this study is that in addition to standard of care treatment (which
includes surgical intervention, antimicrobial therapy and critical care support for organ
dysfunction or failure), AB103 will demonstrate a clinically significant treatment benefit
over placebo.
This hypothesis will be addressed by measuring the effect of AB103 on a composite of clinical
parameters associated with the disease course of patients with NSTI, using a responder
analysis. A responding patient must meet all 5 parameters of the composite clinical success
end point, while a non-responding patient can fail by not meeting any one of the parameters.
These analyses are designed to demonstrate that in addition to being safe, one dose of 0.5
mg/kg of AB103 will:
Improve systemic signs of the infection by improving organ function of patients compared to
placebo as measured by:
- Survival at Day 28
- Modified SOFA (mSOFA) score on Day 14 and change from baseline to Day 14 ≥ 3. A Day 14
mSOFA score of ≤1 and a change from baseline (pre-treatment) to Day 14 ≥3 will be
required for a patient to achieve the primary composite clinical success endpoint
(NICCE)
Improve the local signs of the infection, as measured by:
- Reduced number of debridements, counted to Day 14. No more than 3 debridements to Day 14
will be required for a patient to achieve composite clinical success
- No amputation after the first debridement (amputation on the first debridement is not
considered a failure). A patient will be required to have had no amputations done after
the first surgical procedure in order to achieve composite clinical success.
290 patients will be recruited into the study and randomized to receive either 0.5 mg/kg
AB103 or placebo in a 1:1 ratio. Randomization will be stratified within center by the
diagnosis of Fournier's Gangrene and mSOFA score category (3-4 vs >4) at screening. The
study will be conducted with interim analyses for futility at 100 patients and safety
monitored by an independent Data Monitoring Board at regular planned intervals.
includes surgical intervention, antimicrobial therapy and critical care support for organ
dysfunction or failure), AB103 will demonstrate a clinically significant treatment benefit
over placebo.
This hypothesis will be addressed by measuring the effect of AB103 on a composite of clinical
parameters associated with the disease course of patients with NSTI, using a responder
analysis. A responding patient must meet all 5 parameters of the composite clinical success
end point, while a non-responding patient can fail by not meeting any one of the parameters.
These analyses are designed to demonstrate that in addition to being safe, one dose of 0.5
mg/kg of AB103 will:
Improve systemic signs of the infection by improving organ function of patients compared to
placebo as measured by:
- Survival at Day 28
- Modified SOFA (mSOFA) score on Day 14 and change from baseline to Day 14 ≥ 3. A Day 14
mSOFA score of ≤1 and a change from baseline (pre-treatment) to Day 14 ≥3 will be
required for a patient to achieve the primary composite clinical success endpoint
(NICCE)
Improve the local signs of the infection, as measured by:
- Reduced number of debridements, counted to Day 14. No more than 3 debridements to Day 14
will be required for a patient to achieve composite clinical success
- No amputation after the first debridement (amputation on the first debridement is not
considered a failure). A patient will be required to have had no amputations done after
the first surgical procedure in order to achieve composite clinical success.
290 patients will be recruited into the study and randomized to receive either 0.5 mg/kg
AB103 or placebo in a 1:1 ratio. Randomization will be stratified within center by the
diagnosis of Fournier's Gangrene and mSOFA score category (3-4 vs >4) at screening. The
study will be conducted with interim analyses for futility at 100 patients and safety
monitored by an independent Data Monitoring Board at regular planned intervals.
Inclusion Criteria:
1. Surgical confirmation of NSTI by attending surgeon;
2. mSOFA score ≥3 (in any one or combination of the 5 major components of SOFA score with
one organ component having a score of at least 2: cardiovascular, respiratory, renal,
coagulation, CNS), measured as close as possible to the first debridement;
3. IV drug administration within 6 hours from the clinical diagnosis and the decision at
the study site, to have an urgent surgical exploration and debridement (drug should
not be administered until surgical confirmation is established);
4. If a woman is of childbearing potential, she must consistently use an acceptable
method of contraception from baseline through Day 28;
5. If a male patient's sexual partner is of childbearing potential, the male patient must
acknowledge that they will consistently use an acceptable method of contraception
(defined above) from baseline through Day 28.
6. Signed and dated ICF as defined by the IRB and, if applicable, California Bill of
Rights. If patient is unable to comprehend or sign the ICF, patient's legally
acceptable representative may sign the ICF
Exclusion Criteria:
1. BMI>51;
2. Patient who has been operated at least once for the current NSTI infection and had a
curative deep tissue debridement;
3. Patients with overt peripheral vascular disease in the involved area ;
4. Diabetic patients with peripheral vascular disease who present with below the ankle
infection;
5. Removed DVT in area of NSTI as an exclusion criteria
6. Patient with burn wounds;
7. Current condition of: (a) Inability to maintain a mean arterial pressure > 50 mmHg
and/or systolic blood pressure > 70 mmHg for at least 1 hour prior to screening
despite the presence of vasopressors and IV fluids or (b) a patient with respiratory
failure such that an SaO2 of 80% cannot be achieved or (c) a patient with refractory
coagulopathy (INR >5) or thrombocytopenia (platelet count <20,000) that does not
partially correct with administration of appropriate factors or blood products;
8. Chronic neurological impairment that leads to a neuro mSOFA component ≥2;
9. Recent cerebrovascular accident in the last 3 months;
10. Patients with cardiac arrest requiring cardiopulmonary resuscitation within the past
30 days;
11. Patient is not expected to survive throughout 28 days of study due to underlying
medical condition, such as poorly controlled neoplasm;
12. Patient or patient's family are not committed to aggressive management of the
patient's condition;
13. Any concurrent medical condition, which in the opinion of the Investigator, may
compromise the safety of the patient or the objectives of the study or the patient
will not benefit from treatment such as:
- CHF {NYHA class III-IV}
- Severe COPD
- Liver dysfunction {Childs-Pugh class C}
- Immunosuppression (see Appendix F, Section 15.6 for list of excluded
immunosuppressive medications)
- Neutropenia < 1,000 cells/mm3not due to the underlying infection
- Idiopathic Thrombocytopenia Purpura
- Receiving or about to receive chemotherapy or biologic anti-cancer treatment
although hormonal manipulation therapies for breast and prostate malignancies are
permitted
- Hematological and lymphatic malignancies in the last 5 years;
14. Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes;
15. Patients with known chronic kidney disease (documented pre-illness creatinine value(s)
≥2.0) or patients receiving renal replacement therapy for chronic kidney disease;
16. Patients that are treated with continuous hemofiltration (e.g. Continuous Veno-Venous
Hemofiltration) for acute kidney dysfunction, not due to NSTI, starting prior to study
drug administration;
17. Pregnant or lactating women;
18. Previous enrollment in a clinical trial involving investigational drug or a medical
device within 30 days;
19. Previous enrollment in this protocol, ATB-202 or the Phase 2 trial of AB103, ATB-201.
We found this trial at
80
sites
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1720 2nd Ave S
Birmingham, Alabama 35233
Birmingham, Alabama 35233
(205) 934-4011
Principal Investigator: Ross M Vander Noot, MD
University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
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185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Peter Fagenholz, MD
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75 Francis street
Boston, Massachusetts 02115
Boston, Massachusetts 02115
(617) 732-5500
Principal Investigator: Reza Askari, MD
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
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1000 Blythe Blvd
Charlotte, North Carolina 28203
Charlotte, North Carolina 28203
(704) 355-2000
Principal Investigator: John Green, MD
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529 West Markham Street
Little Rock, Arkansas 72205
Little Rock, Arkansas 72205
(501) 686-7000
Principal Investigator: Kevin Sexton, MD
University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) in...
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1211 Medical Center Dr
Nashville, Tennessee 37232
Nashville, Tennessee 37232
(615) 322-5000
Principal Investigator: Addison May, MD
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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22 Bramhall St
Portland, Maine 04102
Portland, Maine 04102
(207) 662-0111
Principal Investigator: Joseph Rappold, MD
Maine Medical Center One of the country's consistently highest rated hospitals is right in your...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Principal Investigator: Martin Schreiber, MD
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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4502 Medical Drive
San Antonio, Texas 78284
San Antonio, Texas 78284
(210) 567-7000
Principal Investigator: Christopher Crane, MD
University of Texas Health Science Center at San Antonio The University of Texas Health Science...
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Albuquerque, New Mexico 87106
Principal Investigator: Howard Yonas, MD
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500 S State St
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
(734) 764-1817
Principal Investigator: Pauline Park, MD
University of Michigan The University of Michigan was founded in 1817 as one of the...
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Atlanta, Georgia
Principal Investigator: Rondi Gelbard, MD
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Augusta, Georgia 30909
Principal Investigator: Bounthavy Homsombath, MD
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1120 15th Street
Augusta, Georgia 30912
Augusta, Georgia 30912
Principal Investigator: Lester Young, MD
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Baltimore, Maryland 21201
Principal Investigator: Sharon Henry, MD
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Baton Rouge, Louisiana
Principal Investigator: Hollis O'Neal, MD
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Bethlehem, Pennsylvania
Principal Investigator: John Lukaszczyk, MD
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Bronx, New York 10461
Principal Investigator: Vance Smith, MD
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Bronx, New York 10467
Principal Investigator: Vance Smith, MD
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Buffalo, New York 14215
Principal Investigator: William Flynn, MD
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1 Cooper Plaza
Camden, New Jersey 08103
Camden, New Jersey 08103
(856) 342-2000
Principal Investigator: Ju Lin Wang, MD
Cooper University Hospital Cooper University Health Care, the clinical campus of Cooper Medical School of...
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Cincinnati, Ohio 45219
Principal Investigator: Timothy Pritts, MD
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Clermont-Ferrand,
Principal Investigator: Jean-Michel Constantin, Pr
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Colorado Springs, Colorado 80909
Principal Investigator: Thomas Schroeppel, MD
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Columbia, Missouri 65211
(573) 882-2121
Principal Investigator: Jacob Quick, MD
University of Missouri T he University of Missouri was founded in 1839 in Columbia, Mo.,...
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281 W. Lane Ave
Columbus, Ohio 43210
Columbus, Ohio 43210
(614) 292-6446
Principal Investigator: David Evans, MD
Ohio State University The Ohio State University’s main Columbus campus is one of America’s largest...
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2201 Inwood Rd
Dallas, Texas 75235
Dallas, Texas 75235
(214) 645-8300
Principal Investigator: Joseph Minei, MD
U.T. Southwestern Medical Center The story of UT Southwestern Medical Center is one of commitment...
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Dayton, Ohio 45409
Principal Investigator: Peter Ekeh, MD
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777 Bannock St
Denver, Colorado 80204
Denver, Colorado 80204
(303) 436-6000
Principal Investigator: Eric Campion, MD
Denver Health Medical Center Denver Health is a comprehensive, integrated organization providing level one care...
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Detroit, Michigan 48201
Principal Investigator: Lawrence Diebel, MD
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Detroit, Michigan 48235
Principal Investigator: Robert Sherwin, MD
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El Paso, Texas 79905
Principal Investigator: Brian Davis, MD
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1001 E 5th St
Greenville, North Carolina 27858
Greenville, North Carolina 27858
(252) 328-6131
Principal Investigator: Eric Toschlog, MD
East Carolina University Whether it's meeting the demand for more teachers and healthcare professionals or...
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Hershey, Pennsylvania 17033
Principal Investigator: Melissa Boltz, MD
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Houston, Texas 77030
Principal Investigator: Stephanie Gordy, MD
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6550 Fannin St
Houston, Texas 77030
Houston, Texas 77030
(713) 790-3311
Principal Investigator: Daniel Bonville, MD
Houston Methodist Hospital Houston Methodist is comprised of a leading academic medical center in the...
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Indianapolis, Indiana 46202
Principal Investigator: Robert Reed, MD
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University of Kentucky The University of Kentucky is a public, land grant university dedicated to...
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11234 Anderson St
Loma Linda, California 92354
Loma Linda, California 92354
(909) 558-4000
Principal Investigator: Richard Catalano, MD
Loma Linda University Medical Center An outgrowth of the original Sanitarium on the hill in...
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Los Angeles, California 90033
Principal Investigator: Demetrios Demetriades, MD
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Los Angeles, California 90502
Principal Investigator: Dennis Kim, MD
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Los Angeles, California 90033
Principal Investigator: Demetrios Demetriades, MD
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500 S Preston St
Louisville, Kentucky
Louisville, Kentucky
(502) 852-5555
Principal Investigator: Brian G Harbrecht, MD
University of Louisville The University of Louisville is a state supported research university located in...
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2160 South 1st Avenue
Maywood, Illinois 60153
Maywood, Illinois 60153
(888) 584-7888
Principal Investigator: Michael Mosier, MD
Loyola University Medical Center Loyola University Health System is committed to excellence in patient care...
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Miami, Florida 33136
Principal Investigator: Nicholas Namias, MD
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Milwaukee, Wisconsin 53226
Principal Investigator: Todd Neideen, MD
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2450 Riverside Ave
Minneapolis, Minnesota 55454
Minneapolis, Minnesota 55454
(612) 273-3000
Principal Investigator: Greg Bielman, MD
University of Minnesota Medical Center, Fairview Improving patients' lives drives the innovation that makes University...
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Minneapolis, Minnesota 55414
Principal Investigator: Frederick Endorf, MD
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20 York St, N20 York St,
New Haven, Connecticut 06520
New Haven, Connecticut 06520
(203) 688-4242
Principal Investigator: Adrian Maung, MD
Yale-New Haven Hospital Relying on the skill and expertise of more than 4,500 university and...
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New Orleans, Louisiana 70112
Principal Investigator: Patrick Greiffenstein, MD
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Oklahoma City, Oklahoma 73104
Principal Investigator: Jason Lees, MD
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101 The City Drive South
Orange, California 92868
Orange, California 92868
714-456-7890
Principal Investigator: Michael Lekawa, MD
University of California, Irvine Medical Center We are UC Irvine Health. We are a devoted...
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1020 Walnut St
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19107
(215) 955-6000
Principal Investigator: Joshua Marks, MD
Thomas Jefferson University We are dedicated to the health sciences and committed to educating professionals,...
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200 Lothrop St
Pittsburgh, Pennsylvania 15213
Pittsburgh, Pennsylvania 15213
Principal Investigator: Jason Sperry, MD
University of Pittsburgh Medical Center UPMC is one of the leading nonprofit health systems in...
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Richmond, Virginia 23298
(804) 828-0100
Principal Investigator: Paula Ferrada, MD
Virginia Commonwealth University Since our founding as a medical school in 1838, Virginia Commonwealth University...
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2315 Stockton Blvd.
Sacramento, California 95817
Sacramento, California 95817
(916) 734-2011
Principal Investigator: Christine S Cocanour, MD
University of California, Davis Medical Center UC Davis Medical Center serves a 65,000-square-mile area that...
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640 Jackson Street
Saint Paul, Minnesota 55101
Saint Paul, Minnesota 55101
Principal Investigator: David Dries, MD
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34800 Bob Wilson Drive
San Diego, California 92103
San Diego, California 92103
Principal Investigator: Leslie Kobayashi, MD
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325 9th Ave
Seattle, Washington 98104
Seattle, Washington 98104
(206) 744-3300
Principal Investigator: Eileen M Bulger, MD
Harborview Medical Center Harborview Medical Center is the only designated Level 1 adult and pediatric...
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Staten Island, New York 10305
Principal Investigator: Stephen Cohn, MD
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110 Irving St NW
Washington, District of Columbia 20010
Washington, District of Columbia 20010
(202) 877-7000
Principal Investigator: Jack A Sava, MD
Washington Hosp Ctr MedStar Washington Hospital Center is a not-for-profit, 926-bed, major teaching and research...
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