Clinical trial NCT01769755: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Crohns Disease
Keywords: Crohn's disease
Fistula
Diarrhea
Colon
Stem cells
Lead sponsor: Celularity Incorporated
Sponsor class: INDUSTRY
First posted: 2013-01-17
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Adverse Events
timeFrame: Up to 1 year
Secondary outcomes:
measure: Clinical Response
timeFrame: Up to 1 year
measure: Clinical Remission
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
state: California
city: Denver
country: United States
facility: University of Colorado Health Science Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University Hospitals of Cleveland
state: Ohio
city: Chattanooga
country: United States
facility: Erlanger Baroness Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: McGuire Veterans Affairs Medical Center
state: Virginia
Study officials:
affiliation: Celularity Incorporated
name: Monica E Luchi, MD
role: STUDY_DIRECTOR
References: