CELGENE: CCT-PDA001-CD-003

Overview

Status: Recruiting
Keywords: Inflammatory Bowel Disease , IBD , Crohn's Disease
IRB Number: 00063846
Specialty: Gastroenterology
Sub Specialties: Inflammatory Bowel Disease/Crohn's/Ulcerative Colitis

Brief Summary

PDA001 is being developed for the treatment of Crohn’s disease (CD), a chronic inflammatory disease of the gastrointestinal tract.

Objectives
The primary objective of the study is to assess the safety and tolerability of ascending doses of IV PDA001 infused every other week for 8 weeks (5 total infusions) in subjects with CD with colonic involvement who are refractory to one or more of the following: oral corticosteroids, immunosuppressants and/or biologic agents. The secondary objective of the study is to estimate the efficacy of the above mentioned dosing regimen in subjects with refractory CD with colonic involvement.
 
The secondary objective of the study is to estimate the efficacy of ascending doses of IV PDA001 infused every other week for 8 weeks (5 total infusions) in subjects with CD with colonic involvement who are refractory to one or more of the following: oral corticosteroids, immunosuppressants and/or biologic agents.
 
The exploratory objectives of the study are:
  • To estimate the efficacy of ascending doses of IV PDA001 infused every other week for 8 weeks (5 total infusions) on mucosal healing (using endoscopic parameters of disease activity) in subjects with refractory CD with colonic involvement.
  • To estimate the treatment effect ascending doses of IV PDA001 infused every other week for 8 weeks (5 total infusions) on health-related quality of life in subjects with refractory CD with colonic involvement.
Certain data from exploratory objectives might not be included in the clinical study report.
 
 
References listed at end of protocol as well as in the "Reference" word document attached to this study
 

Principal Investigator: John Valentine
Department: Gastroenterology
Co Investigator:

Contact Information

Name:Andrew Grandemange
Phone: 8015879092
Email: andrew.grandemange@hsc.utah.edu

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

1. Males and females 18 - 75 years of age at the time of signing the informed consent document.

2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Minimum weight of 40 kg at screening.

5. A female of childbearing potential (FCBP)† must have a negative urine pregnancy test at screening (Visit 1) and immediately prior to all doses of IP. In addition, sexually active FCBP must agree to use two of the following adequate forms of contraception methods such as: oral, injectable or implantable hormonal contraception; tubal ligation; intrauterine device; barrier contraceptive with spermicide; or vasectomized partner for the duration of the study and the follow-up period. A FCBP must agree to have pregnancy tests at all scheduled study visits. Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP for the duration of the study and the follow-up period.

6. If female and of childbearing age, subject must be non-pregnant, non-breastfeeding, and use adequate contraception. If male, subject must use adequate contraception.

7. Subject must have inflammatory CD with colonic involvement diagnosed at least 6 months but no greater than 15 years prior to treatment with IP.

8. Subject must have confirmation of ongoing CD by ileocolonoscopy at screening. 

9. Subject must have a CDAI score ≥ 220 and ≤ 450 as assessed between Visit 1 and Visit 2.

10. The subject must have failed, ie, in the judgment of the investigator had an inadequate response or lost response (recurrence of symptoms) to an approved Crohn’s disease agent at any time. See Table 3 for the doses and length of treatment which define an adequate trial of each agent. 

 
Table 3
Drug Length of Trial Dose

Andtimetabolics

Azathioprin

Mercaptopurine

 

12 weeks

12 weeks

 

2-3 mg/kg/day

1.0-1.5 mg/kg/day

Salicylates

Sulfasalazine

Mesalamine

 

56 days

56 days

 

4 grams/day

1.5 mg/kg/day

Steroids

Prednisone (or equivalent)

 

28 days

 

20 mg/day

Biologics

Adalimumab

Infliximab

Golimumab

Certolizumab

 

3 months

 

Approved dose and schedule

 

 

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

 
1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
 
2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he or she were to participate in the study.
 
3. Any condition that confounds the ability to interpret data from the study.
 
4. Pregnant or lactating females.
 
5. Morbidly obese subjects (subjects with a BMI > 35 at screening).
 
6. AST or ALT > 2.5 x the upper limit of normal at screening.
 
7. Serum creatinine concentration > 2.0 mg/dl at screening.
 
8. Alkaline phosphatase > 2.5 x the upper limit of normal at screening.
 
9. Bilirubin level > 2 mg/dL (unless subject has known Gilbert’s disease).
 
10. Untreated chronic infection 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 CD are allowed.
 
11. Organic heart disease (eg, congestive heart failure) or clinically significant abnormal findings on ECG.
 
12. Clinically significant arrhythmia.
 
13. Documented prior history of neurological disease or evidence of ongoing neurological disease.
14. 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).
 
15. Subject has had a stricture of the bowel requiring hospitalization within 182 days (6 months) prior to treatment with IP.
 
16. Subject has had bowel surgery other than perianal (for example, fistulotomy, seton placement, or abscess drainage) or previous abscess drainage within 182 days (6 months) prior to treatment with IP.
 
17. Subject tests positive for Clostridium difficile toxin at screening.
 
18. Any surgery within 28 days prior to treatment with IP.
 
19. Subject has a colostomy, ileostomy or ileal pouch anal anastomosis.
 
20. 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 IP.
 
21. Subject has received previous cell therapy.
 
22. Subject is expecting to have elective surgery at any time between Visit 1 (screening) and Visit 7 (end of induction phase).
 
23. Subject has a concurrent diagnosis of ulcerative colitis.
 
24. Subject has a known hypersensitivity to bovine or porcine products.
 
25. Subject has a known hypersensitivity to hydrocortisone and/or diphenhydramine (Benadryl®) and/or enoxaparin sodium (Lovenox®) and/or heparin.
 
26. Subjects with known history of heparin-induced thrombocytopenia.
 
27. Subjects with protein C or S deficiency.
 
28. Subjects with prior history of thrombophlebitis or other pathological arterial or venous thrombosis.