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

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

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.

Study Overview

• Status: Completed
• Conditions: Crohns Disease
• Intervention / Treatment: Biological: PDA001; Drug: Vehicle Controlled Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
  • Colorado
    • Denver, Colorado, United States, 80220-3706
      • University of Colorado Health Science Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
  • New York
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University Hospitals of Cleveland
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Baroness Hospital
    • Nashville, Tennessee, United States, 37232-5505
      • Vanderbilt - Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire Veterans Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of participants experiencing adverse events during the initial and extended follow-up periods	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response	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.	Up to 1 year
Clinical Remission	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score CDAI score of ≤ 150 points	Up to 1 year

Collaborators and Investigators

• Sponsor: Celularity Incorporated

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: January 15, 2013
• First Submitted That Met QC Criteria: January 16, 2013
• First Posted (ESTIMATE): January 17, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2018
• Last Update Submitted That Met QC Criteria: February 27, 2018
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Diarrhea; Stem cells; Crohn's disease; Fistula; Colon
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: CCT-PDA001-CD-003