CD101 Compared to Caspofungin Followed by Oral Step Down in Subjects With Candidemia and/or Invasive Candidiasis-Bridging Extension

NCT02734862 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CD101.IV.2.032015-005599-51
• Study Type: interventional
• Target: 207
• Locations: 10 countries
• Sites: 63

Brief Summary

The purpose of this study is to determine if intravenous CD101 is safe and effective in the treatment of candidemia and/or invasive candidiasis when compared to caspofungin (followed by oral fluconazole).

Conditions

Candidemia; Mycoses; Fungal Infection; Fungemia; Invasive Candidiasis

Keywords

mycoses

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]

  Number of Subjects with Incidence of Treatment Emergent Adverse Events based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and ECG abnormalities.

  From first dose of study drug through Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia.

• Resolution of Systemic Signs Attributable to Candidemia and/or Invasive Candidiasis and Mycological Eradication [Overall Success]

  Number of subjects with mycological eradication and complete resolution of all systemic signs of candidemia and/or invasive candidiasis which were present at baseline

  Day 14 (± 1 day)

Secondary Outcomes (6)

• Mycological Eradication and Resolution of Systemic Signs

  Day 5, and Follow-up (FU Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia.

• Mycological Eradication

  Day 5, Day 14 (±1 day), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia)

• Clinical Cure

  Day 14 (±1 day) and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia).

• Evaluate PK (Cmax)

  Day 1, 10 minutes before end of infusion (EOI)

• Evaluate PK (Cmin)

  Day 8, predose

Study Arms (3)

Group 1

EXPERIMENTAL

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed. Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

Drug: CD101; Drug: intravenous placebo; Drug: oral placebo

Group 3

ACTIVE COMPARATOR

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia). After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg \[4 capsules\] on the first day followed by 400 mg \[2 capsules\]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Drug: Caspofungin; Drug: Fluconazole; Drug: intravenous placebo

Group 2

EXPERIMENTAL

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed. Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

Drug: CD101; Drug: intravenous placebo; Drug: oral placebo

Interventions

CD101 DRUG

Intravenous antifungal therapy

Also known as: CD101 for Injection

Group 1; Group 2

Caspofungin DRUG

Intravenous antifungal therapy

Also known as: Cancidas

Group 3

Fluconazole DRUG

oral antifungal therapy

Also known as: generic fluconazole

Group 3

intravenous placebo DRUG

normal saline

Also known as: placebo infusion

Group 1; Group 2; Group 3

oral placebo DRUG

microcrystalline cellulose

Also known as: encapsulated cellulose

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• mycological diagnosis of candidemia and/or invasive candidiasis from a sample taken less than or equal to 96 hours before randomization (defined as: at least 1 blood culture positive for Candida or positive test for Candida from a sponsor approved rapid diagnostic test or positive gram stain for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site)
• willing to initiate or continue medical treatment to cure infections, including receipt of antibiotics and surgical procedures, if required. Patients receiving only medications and measures for comfort and not cure should not be enrolled.
• female subjects of child bearing potential \<2 years post menopausal must agree to one barrier method and one highly effective method of birth control or sexual abstinence.
• male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and also agree not to donate sperm from first dose of CD101 (Day 1) until 90 days following last administration of study drug.
• willing and able to provide written informed consent. If the subject is unable to consent for himself/herself, a legally acceptable representative must provide informed consent on their behalf.
• presence of one or more systemic signs attributable to candidemia and/or invasive candidiasis

You may not qualify if:

• Any of the following forms of IC:
• Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed)
• Osteomyelitis
• Endocarditis or myocarditis
• Meningitis, endophthalmitis, or any central nervous system infection
• neutropenia
• alanine aminotransferase or aspartate aminotransferase levels \>10 fold the upper limit of normal
• severe hepatic impairment in subjects with a history of chronic cirrhosis
• greater than 48 hours systemic antifungal treatment at approved doses to treat candidemia
• pregnant females
• lactating females who are nursing
• known hypersensitivity to CD101, caspofungin, any echinocandin, or to any of their excipients
• previous participation in this or any previous CD101 study
• recent use of an investigational medicinal product within 28 days of first dose of study drug or presence of an investigational device at the time of screening
• Principal Investigator considers the subject should not participate

Sponsors & Collaborators

• Cidara Therapeutics Inc.: lead

Study Sites (63)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California - Davis

Davis, California, 95817, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Harper University Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercury Street Medical

Butte, Montana, 59701, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Mercy Health - St. Vincent Medical Center - ID Clinical Research

Toledo, Ohio, 43608, United States

Location

Reading Hospital and Medical Center

West Reading, Pennsylvania, 19611, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Virginia Tech, Carillion School of Medicine

Roanoke, Virginia, 24016, United States

Location

Jules Bordet Institute

Brussels, 1000, Belgium

Location

CHU Brugman

Brussels, 1020, Belgium

Location

Erasme Hospital

Brussels, 1070, Belgium

Location

UCL Saint-LUC

Brussels, 1200, Belgium

Location

UZ Gent Algemene Inwendige Zietken

Ghent, 9000, Belgium

Location

University Hospital Brussels

Jette, 1090, Belgium

Location

University Hospital Leuven

Leuven, 3000, Belgium

Location

CHU Sart-Tillman

Liège, 4000, Belgium

Location

University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Clinical Hematology

Sofia, 1431, Bulgaria

Location

University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Burns and Plastic Surgery Clinic, Department of Anesthesiology and Intensive Care

Sofia, 1606, Bulgaria

Location

Juravinski Hospital and Cancer Centre/Hamilton Health Sciences

Hamilton, Ontario, L8V 1C3, Canada

Location

Toronto General Hospital-University Health Network

Toronto, Ontario, M5G 2N2, Canada

Location

CIUSSS de L'Est-de-l'Île-De-Montréal, Installation Hôpital

Montreal, Quebec, H1T 2M4, Canada

Location

McGill University Health Centre-Research Institute

Montreal, Quebec, H4A 3J1, Canada

Location

University General Hospital "Attikon", 2nd Department of Critical Care

Athens, Chaidari, 12 462, Greece

Location

General Hospital of Athens "Evangelismos", 5th Department of Internal Medicine and Infectious Diseases Unit

Athens, 10676, Greece

Location

Laiko General Hospital of Athens

Athens, 115 27, Greece

Location

Henry Dunant Hospital Center

Athens, 11526, Greece

Location

General Hospital of Athens "Evangelismos", Department of Critical Care

Athens, Greece

Location

University Hospital of Larissa, Department of Critical Care Unit

Thessaloniki, 41110, Greece

Location

Medical Centre, Hungarian Defence Forces, Central Intensive Care Unit and Anesthesiology Department

Budapest, 1134, Hungary

Location

Fejer County St. Gyorgy University Teaching Hospital, Central Department of Anesthesiology and Intensive Care Unit

Szeged, 6725, Hungary

Location

Polyclinic S. Orsola-Malpighi, Department of Organ Impairment and Transplants, Operative Unit of Infectious Diseases

Bologna, 40138, Italy

Location

University Polyclinic Hospital of Modena, Department of General and Specialist Surgery, Operative Unit of Anesthesia and Intensive Care I

Modena, 41124, Italy

Location

University Hospital of Pisa, Department of Gastroenterology and Infectious Diseases, Operative Unit of Infectious Diseases

Pisa, 56124, Italy

Location

University Polyclinic Agostino Gemelli, Complex Operative Unit of Infectious Diseases 2

Rome, 00168, Italy

Location

Hospital Maggiore University Hospital Ospedali Riuniti of Trieste Dept of ID

Trieste, 34125, Italy

Location

University Hospital "Santa Maria della Misericordia" of Udine, Department of Specialist Medicine, Clinic of Infectious Diseases

Udine, 33100, Italy

Location

Craiova County Emergency Clinical Hospital, ATI Clinic

Craiova, Dolj, 200642, Romania

Location

Institute of Infectious Diseases

Bucharest, Sector 2, 021105, Romania

Location

Pius Brinzeu County Emergency Clinical Hospital, Anesthesia and Intensive Care Department (Romania)

Timișoara, Timiș County, 300723, Romania

Location

Sfanta Parascheva Parascheva Iasi Clinical Hospital for Infectious Diseases

Iași, 700116, Romania

Location

Kuban State Medical University

Krasnodar, 350063, Russia

Location

Territorial Clinical Hospital

Krasnoyarsk, 660022, Russia

Location

Mariinskaya City Hospital

Saint Petersburg, 191104, Russia

Location

University Hospital Vall d'Hebron (HUVH), Department of Infectious Diseases

Barcelona, Catalonia, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona, Department of Infectious Diseases

Barcelona, Catalonia, 08036, Spain

Location

University Hospital Cruces, Unit of Infectious Diseases

Barakaldo, 48903, Spain

Location

Hospital del Mar, Department of Infectious Diseases

Barcelona, 08003, Spain

Location

General University Hospital Gregorio Maranon

Madrid, 28007, Spain

Location

University Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

University Hospital Clinical San Carlos

Madrid, 28040, Spain

Location

University Hospital La Paz

Madrid, 28046, Spain

Location

University Hospital Virgen Macarena

Seville, 41009, Spain

Location

University Hospital Nuestra Senora de Valme,

Seville, 41014, Spain

Location

University Hospital Virgen del Rocio (HUVR)

Seville, Spain

Location

University Hospital La Fe

Valencia, 46026, Spain

Location

Related Publications (5)

• Honore PM, Bassetti M, Cornely OA, Dupont H, Fortun J, Kollef MH, Pappas P, Pullman J, Vazquez J, Bielicka I, Dickerson S, Manamley N, Sandison T, Thompson GR. Length of hospital and intensive care unit stay in patients with invasive candidiasis and/or candidemia treated with rezafungin: a pooled analysis of two randomised controlled trials. Crit Care. 2024 Nov 11;28(1):361. doi: 10.1186/s13054-024-05152-2.

  PMID: 39529079 DERIVED

• Honore PM, Girardis M, Kollef M, Cornely OA, Thompson GR 3rd, Bassetti M, Soriano A, Huang H, Vazquez J, Kullberg BJ, Pappas PG, Manamley N, Sandison T, Pullman J, Nseir S. Rezafungin versus caspofungin for patients with candidaemia or invasive candidiasis in the intensive care unit: pooled analyses of the ReSTORE and STRIVE randomised trials. Crit Care. 2024 Oct 28;28(1):348. doi: 10.1186/s13054-024-05117-5.

  PMID: 39468640 DERIVED

• Smith HL, Bensman TJ, Mishra S, Li X, Dixon CA, Sheikh J, McMaster OG, Joshi A, Rubin DB, Goodwin A, Miller TJ, Danielsen ZY, Syed I, Shukla SJ, Iarikov D, Kim PW, Farley JJ. Regulatory Considerations in the Approval of Rezafungin (Rezzayo) for the Treatment of Candidemia and Invasive Candidiasis in Adults. J Infect Dis. 2024 Aug 16;230(2):505-513. doi: 10.1093/infdis/jiae146.

  PMID: 38502709 DERIVED

• Thompson GR 3rd, Soriano A, Honore PM, Bassetti M, Cornely OA, Kollef M, Kullberg BJ, Pullman J, Hites M, Fortun J, Horcajada JP, Kotanidou A, Das AF, Sandison T, Aram JA, Vazquez JA, Pappas PG. Efficacy and safety of rezafungin and caspofungin in candidaemia and invasive candidiasis: pooled data from two prospective randomised controlled trials. Lancet Infect Dis. 2024 Mar;24(3):319-328. doi: 10.1016/S1473-3099(23)00551-0. Epub 2023 Nov 23.

  PMID: 38008099 DERIVED

• Thompson GR, Soriano A, Skoutelis A, Vazquez JA, Honore PM, Horcajada JP, Spapen H, Bassetti M, Ostrosky-Zeichner L, Das AF, Viani RM, Sandison T, Pappas PG. Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial. Clin Infect Dis. 2021 Dec 6;73(11):e3647-e3655. doi: 10.1093/cid/ciaa1380.

  PMID: 32955088 DERIVED

MeSH Terms

Conditions

Candidemia; Mycoses; Fungemia; Candidiasis, Invasive

Interventions

Injections; Caspofungin; Fluconazole

Condition Hierarchy (Ancestors)

Candidiasis; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Echinocandins; Peptides, Cyclic; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Taylor Sandison, M.D., MPH
• Organization: Cidara Therapeutics, Inc.

clinicaltrialinfo@cidara.com

858-888-7868

Study Officials

• Taylor Sandison, MD MPH

  Cidara Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: March 16, 2016
• First Posted: April 12, 2016
• Study Start: July 26, 2016
• Primary Completion: June 1, 2019
• Study Completion: July 1, 2019
• Last Updated: December 8, 2020
• Results First Posted: December 8, 2020

Record last verified: 2020-12

Locations

CA (4); US (16); RU (3); IT (6); BU (2); BE (8); GR (6); HU (2); RO (4); ES (12)