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 Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Crohns Disease

Intervention / Treatment
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* Biological: PDA001
* Drug: Vehicle Controlled Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Placenta-Derived Cells PDA001 Intravenous Infusion<br>Intravenous infusion of Human Placenta-Derived Cells PDA001 over the course of 2 hours. | Biological: PDA001<br>* 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.<br>|
| Placebo Comparator: Vehicle controlled placebo<br>Intravenous infusion of Vehicle Controlled Placebo over the course of 2 hours | Drug: Vehicle Controlled Placebo<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's disease, Fistula, Diarrhea, Colon, Stem cells