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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

Phase 1
Completed
Conditions
Crohns Disease
Interventions
Drug: Vehicle Controlled Placebo
Biological: PDA001
Registration Number
NCT01769755
Lead Sponsor
Celularity Incorporated
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
14
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vehicle controlled placeboVehicle Controlled PlaceboIntravenous infusion of Vehicle Controlled Placebo over the course of 2 hours
Human Placenta-Derived Cells PDA001 Intravenous InfusionPDA001Intravenous infusion of Human Placenta-Derived Cells PDA001 over the course of 2 hours.
Primary Outcome Measures
NameTimeMethod
Adverse EventsUp to 1 year

Number of participants experiencing adverse events during the initial and extended follow-up periods

Secondary Outcome Measures
NameTimeMethod
Clinical ResponseUp to 1 year

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 RemissionUp to 1 year

Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score CDAI score of ≤ 150 points

Trial Locations

Locations (12)

McGuire Veterans Affairs Medical Center

🇺🇸

Richmond, Virginia, United States

Cedars Sinai Medical Center, Inflammatory Bowel Disease Center

🇺🇸

Los Angeles, California, United States

University of Miami School of Medicine

🇺🇸

Miami, Florida, United States

Case Western Reserve University Hospitals of Cleveland

🇺🇸

Cleveland, Ohio, United States

University of Cincinnati Medical Center

🇺🇸

Cincinnati, Ohio, United States

Vanderbilt - Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

Erlanger Baroness Hospital

🇺🇸

Chattanooga, Tennessee, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

University of Colorado Health Science Center

🇺🇸

Denver, Colorado, United States

Rochester General Hospital

🇺🇸

Rochester, New York, United States

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