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

• ClinicalTrials.gov Identifier: NCT01769755
• Recruitment Status: Completed
• First Posted: January 17, 2013
• Last Update Posted: March 1, 2018
• Sponsor: Celularity Incorporated
• Information provided by (Responsible Party): Celularity Incorporated

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Crohns Disease	Biological: PDA001; Drug: Vehicle Controlled Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: March 2013
• Actual Primary Completion Date: November 2014
• Actual Study Completion Date: November 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Adverse Events [ Time Frame: Up to 1 year ]
   Number of participants experiencing adverse events during the initial and extended follow-up periods

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Chattanooga, 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

Celularity Incorporated

Investigators

• Study Director: Monica E Luchi, MD; Celularity Incorporated

More Information

• Responsible Party: Celularity Incorporated
• ClinicalTrials.gov Identifier: NCT01769755
• Other Study ID Numbers: CCT-PDA001-CD-003
• First Posted: January 17, 2013
• Last Update Posted: March 1, 2018
• Last Verified: August 2015

Keywords provided by Celularity Incorporated:

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