A Randomized, Double-Blind, Placebo-Controlled Dose-Escalation Study to Determine the Safety and Efficacy of Intravenous Infusion of Human Placenta-Derived Cells (PDA001) for the Treatment of Crohn's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene ( Celgene Corporation )
ClinicalTrials.gov Identifier:
NCT01769755
First received: January 15, 2013
Last updated: August 17, 2015
Last verified: August 2015
  Purpose
To assess the safety and efficacy of intravenous (IV) PDA001 infused every two weeks for up to 5 total infusions in subjects with Crohn's disease who are refractory to one or more standard Crohn's disease therapies.

Condition Intervention Phase
Crohns Disease
Biological: PDA001
Drug: Vehicle Controlled Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Dose Escalation Study to Determine the Safety and Efficacy of Intravenous Infusion of Human Placenta-Derived Cells (PDA001) for the Treatment of Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Celgene:

Primary Outcome Measures:
  • Adverse Events [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Number of participants experiencing adverse events during the initial and extended follow-up periods


Secondary Outcome Measures:
  • Clinical Response [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A clinical response is defined as a reduction from baseline by 25% and/or ≥ 100 points in the Crohn's Disease Activity Index (CDAI) score. The Crohn's Disease Activity Index or CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease.

  • Clinical Remission [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score CDAI score of ≤ 150 points


Enrollment: 14
Study Start Date: March 2013
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Human Placenta-Derived Cells PDA001 Intravenous Infusion
Intravenous infusion of Human Placenta-Derived Cells PDA001 over the course of 2 hours.
Biological: PDA001

Cohort 1 Dose Level 1: ¼ unit Human Placenta-Derived Cells PDA001 infused a total of 5 times 2 weeks apart.

Cohort 2 Dose Level 2: ½ unit Human Placenta-Derived Cells PDA001 infused a total of 5 times 2 weeks apart.

Cohort 3 Dose Level 3: 1 unit Human Placenta-Derived Cells PDA001 infused a total of 5 times 2 weeks apart.

Placebo Comparator: Vehicle controlled placebo
Intravenous infusion of Vehicle Controlled Placebo over the course of 2 hours
Drug: Vehicle Controlled Placebo

Cohort 1 Dose Level 1: ¼ unit vehicle controlled placebo infused a total of 5 times 2 weeks apart.

Cohort 2 Dose Level 2: ½ unit vehicle controlled placebo infused a total of 5 times 2 weeks apart.

Cohort 3 Dose Level 3: 1 unit vehicle controlled placebo infused a total of 5 times 2 weeks apart.


Detailed Description:
This is a randomized, double-blind, placebo-controlled, dose-escalation study to study 3 cohorts of subjects with Crohn's Disease including (but not limited to) those with colonic involvement. Each cohort (n = 9) will include PDA001 treated subjects (n = 6) as well as placebo (vehicle control) treated subjects (n = 3). Cohorts will be enrolled sequentially, beginning with the lowest dose cohort (1/4 unit PDA001) and progressing until the maximum tolerated dose of IV PDA001 is determined.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • • Males and females 18 - 75 years of age at the time of signing the informed consent document.

    • Minimum weight of subject is 40 kg at screening.
    • Subject must have inflammatory Crohn's Disease (CD) diagnosed at least 6 months but no greater than 15 years prior to treatment with Investigational Product (IP).
    • Subject must have confirmation of ongoing CD by ileocolonoscopy at screening.
    • Subject must have a Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450 as assessed between Visit 1 and Visit 2.

Exclusion Criteria:

  • Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study including but not limited to

    • Liver Function Tests Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 2.5 x the upper limit of normal at screening.
    • Serum creatinine concentration > 2.0 mg/dl at screening. Alkaline phosphatase > 2.5 x the upper limit of normal at screening.
    • Bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease).
  • Pregnant or lactating females.
  • Morbidly obese subjects Body Mass Index (BMI) > 35 at screening).
  • Subject has untreated chronic infection including Clostridium difficile toxin positive at screening or treatment of any infection with antibiotics within 4 weeks prior to dosing with IP (other than a treated urinary tract infection or drained perianal abscess). Note: Stable doses of antibiotics used to treat Crohn's Disease are allowed.
  • Subject has organic heart disease (eg, congestive heart failure), clinically significant arrhythmia or clinically significant abnormal findings on Electrocardiograms (ECG).
  • Subject has a history of other malignancies within 5 years (except basal cell carcinoma of the skin that is surgically cured, remote history of cancer now considered cured or positive Pap smear with subsequent negative follow up).
  • Subject has had a stricture of the bowel requiring hospitalization within 182 days prior to treatment with IP.
  • Subject has had bowel surgery other than perianal (for example, fistulotomy, seton placement, or abscess drainage) or previous abscess drainage within 182 days prior to treatment with IP.
  • Subject has had any surgery within 28 days prior to treatment with IP.
  • Subject has a colostomy, ileostomy or ileal pouch anal anastomosis.
  • Subject has received an investigational agent —an agent or device not approved by FDA for marketed use in any indication—within 90 days (or 5 half-lives, whichever is longer) prior to treatment with investigational product.
  • Subject has received previous cell therapy.
  • Subject is expecting to have elective surgery at any time between Visit 1 (screening) and Visit 7 (end of induction phase).
  • Subject has concurrent diagnosis of ulcerative colitis.
  • Subjects with protein C or S deficiency.
  • Subjects with prior history of thrombophlebitis or other pathological arterial or venous thrombosis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01769755

Locations
United States, California
Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
Los Angeles, California, United States, 90048
United States, Colorado
University of Colorado Health Science Center
Denver, Colorado, United States, 80220-3706
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami School of Medicine
Miami, Florida, United States, 33136
United States, New York
Rochester General Hospital
Rochester, New York, United States, 14621
United States, Ohio
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
United States, Tennessee
Erlanger Baroness Hospital
Chattangooga, Tennessee, United States, 37403
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, United States, 37232-5505
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
McGuire Veterans Affairs Medical Center
Richmond, Virginia, United States, 23249
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Steven Fischkoff, MD Celgene
  More Information

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01769755     History of Changes
Other Study ID Numbers: CCT-PDA001-CD-003 
Study First Received: January 15, 2013
Last Updated: August 17, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene:
Crohn's disease
Fistula
Diarrhea
Colon
Stem cells

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on August 22, 2016