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

Crohns Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01769755
• Other study ID #: CCT-PDA001-CD-003
• Status: Completed
• Phase: Phase 1
• First received: January 15, 2013
• Last updated: February 27, 2018
• Start date: March 2013
• Est. completion date: November 2014

Study information

• Verified date: August 2015
• Source: Celularity Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohns Disease

Intervention

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.

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.

Locations

Country	Name	City	State
United States	Erlanger Baroness Hospital	Chattanooga	Tennessee
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University Hospitals of Cleveland	Cleveland	Ohio
United States	University of Colorado Health Science Center	Denver	Colorado
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
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	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee
United States	McGuire Veterans Affairs Medical Center	Richmond	Virginia
United States	Rochester General Hospital	Rochester	New York
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Celularity Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Number of participants experiencing adverse events during the initial and extended follow-up periods	Up to 1 year
Secondary	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
Secondary	Clinical Remission	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score CDAI score of = 150 points	Up to 1 year