Biomarkers Consortium - Developing Endpoints for Clinical Trials in CABP and Skin Infections

The Biomarkers Consortium - Developing Endpoints for Clinical Trials in CABP and Skin Infections aims to develop approaches that will help the U.S. Food and Drug Administration (FDA) develop efficacy outcome measures (endpoints) for modern-day clinical trials of investigational agents for community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) that can be tied to historical data in each indication, thereby providing the basis for sound non-inferiority (NI) trial design and NI margin justification. A key deliverable includes the development and content validity of a Patient-Reported Outcome (PRO) draft instrument for CABP and ABSSSI to use as a tool to assess how a patient feels, functions and survives in anti-infective clinical trials and studies. Identification and validation of effective approaches to measuring these endpoints and any related biomarkers will be important to project success.

Goals

  • Develop reliable and well-defined clinically relevant endpoints for clinical trials of antibiotics for treatment of CABP and ABSSSI, two common and serious bacterial infections.
  • Complete the content validity phase of a Patient-Reported Outcome measure for each of the ABSSI and CABP indications.

Results & Accomplishments

The FNIH CABP/ABSSSI Project Team confirmed relevant outcome measures for CABP and ABSSSI through retrospective analyses and synthesis of data from modern day clinical trials. Analysis of these data were submitted and incorporated into the FDA guidance to include symptomatic endpoints for CABP and ABSSSI. Thus far, four antibiotic drugs were approved using the updated FDA guidance. The CABP and ABSSSI Patient Reported Outcome draft instruments are complete, and the project has received $1.8M in support from FDA to evaluate the psychometric properties of each tool.

Guidance Documents

Guidance for Industry: Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.

Draft Guidance for Industry: Community-Acquired Bacterial Pneumonia: Developing Drugs for Treatment. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.

Scientific Publications

Patient-Reported Outcome Assessments as Endpoints in Studies in Infectious Diseases. Powers JH, Howard K, Saretsky T, Clifford S, Hoffmann S, Llorens L, Talbot G. Clin Infect Dis. 2016 Aug 15;63 Suppl 2:S52-6. doi: 10.1093/cid/ciw317. PMID: 27481954

Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health. Talbot GH, Powers JH, Hoffmann SC; Biomarkers Consortium of the Foundation for the National Institutes of Health CABP-ABSSSI and HABP-VABP Project Teams. Clin Infect Dis. 2016 Mar 1;62(5):603-7. doi: 10.1093/cid/civ927. PMID: 26668337

Progress on developing endpoints for registrational clinical trials of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections: update from the Biomarkers Consortium of the Foundation for the National Institutes of Health. Talbot GH, Powers JH, Fleming TR, Siuciak JA, Bradley J, Boucher H; CABP-ABSSSI Project Team. Clin Infect Dis. 2012 Oct;55(8):1114-21. Review. PMID: 22744885

Posters

Development of a Patient-Reported Outcome instrument (SKINFECT-PRO) to standardize and quality symptoms of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). Powers JH, Howard K, Saretsky T, Clifford S, Hoffmann SC, Talbot GH, Cimms TA, Llorens L, FNIH Biomarkers Consortium CABP ABSSSI Project Team. Presented at ISPOR 20th Annual International Meeting May 1620, 2015, Philadelphia, PA.

Community-Acquired Bacterial Pneumonia (CABP): Development of a new Patient-Reported Outcome (PRO) Measure. Howard K, Clifford S, Powers JH, Saretsky TL, Hoffmann SC, Llorens L, Talbot GH, Cimms TA, FNIH Biomarkers Consortium CABP ABSSSI Project Team. Presented at ISPOR 20th Annual International Meeting May 1620, 2015, Philadelphia, PA.

Media

Editorial Commentary: A Collaborative Model for Endpoint Development: Advancing the Science of Antibacterial Drug Clinical Trials. Toerner JG, Cox E. Clin Infect Dis. 2016 Mar 1;62(5):608-9. doi: 10.1093/cid/civ1007.

A collaborative model for endpoint development for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Toerner JG, Burke L, Komo S, Papadopoulos E. Clin Infect Dis. 2012 Oct;55(8):1122-3.

ICON Press Release (Feb. 20, 2017):ICON Selected by the FDA to Validate Patient-Reported Outcome Endpoints for Antibacterial Drug Trials

Partners

Actelion Pharmaceuticals Ltd.
American Thoracic Society
AstraZeneca Pharmaceuticals LP
Basilea Pharmaceutica International Ltd.
Cempra Pharmaceuticals
Cerexa, Inc.
Cubist Pharmaceuticals, Inc.
Durata Therapeutics, Inc.
Food and Drug Administration
ICON plc.
Infectious Diseases Society of America
Janssen, L.P.
The Medicines Company
Merck Sharp & Dohme Corp.
Nabriva Therapeutics AG
Trius Therapeutics, Inc.
National Institute of Allergy and Infectious Diseases (NIAID)
Pfizer Inc
Pharmaceutical Research and Manufacturers of America
Theravance BioPharma

Contact

Steve Hoffmann, Scientific Program Manager, Inflammation and Immunity, shoffmann@fnih.org

Stephanie Cush, Ph.D., Scientific Project Manager, scush@fnih.org