A Pilot Study of FFP104 in Subjects With Crohn's Disease

Crohn's Disease Clinical Trial

Official title:

A Phase II, Double-blind, Randomised, Placebo-controlled, Parallel Group Pilot Study to Evaluate the Safety and Efficacy of FFP104 in the Treatment of Subjects With Moderate to Severely Active Crohn's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02465944
• Other study ID #: FFP104-002
• Secondary ID: 2015-001678-17
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: May 18, 2015
• Last updated: August 23, 2016
• Start date: January 2016
• Est. completion date: December 2017

Study information

• Verified date: August 2016
• Source: Fast Forward Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

This study will be conducted to evaluate the safety, tolerability and efficacy of intravenously administered FFP104 or placebo over 15 days (3 total doses) in subjects with moderate to severely active Crohn's Disease

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria

Subjects will be entered into this study only if they meet all of the following criteria:

• Willing and able to provide written informed consent.

• Willing and able to comply with all study procedures and visits.

• Male or female aged between 18 and 75 years, inclusive.

• Body Mass Index (BMI) between 18-35 kg/m2.

• Clinical diagnosis of Crohn's disease involving the colon and/or ileum for at least 3 months from Screening confirmed by radiological, endoscopic or histological evidence.

• Active Crohn's disease defined as a Crohn's Disease Activity Index (CDAI) score from 220 and 450, inclusive, at Screening.

• Active inflammatory disease as defined by Crohn's Disease Endoscopic Index of Severity (CDEIS) = 8 (as determined by a Central Blinded Reader) at Screening.

• Tumor Necrosis Factor (TNF)-naïve or previously exposed to a single anti-TNF agent (such as infliximab, adalimumab or certolizumab pegol) with treatment discontinued at least 8 weeks prior to Screening due to inadequate response, loss of response or intolerance as judged by the Investigator.

• Must have adequate renal and hepatic function as adjudged by the Investigator.

• In good health (other than Crohn's disease) as evidenced by medical history and physical examination.

Exclusion criteria

Subjects will be entered into this study only if they meet none of the following criteria:

• Subjects who are pregnant, breastfeeding, or of child-bearing potential and not using a medically accepted form of contraception.

• Presence of fistulas, ileostomies, colostomies or rectal pouches or history of proctocolectomy or total colectomy. Subject has an ostomy or ileoanal pouch (subjects with a previous ileorectal anastomosis are not excluded).

• Subject has short bowel syndrome as determined by the Investigator.

• History of evidence of colonic mucosal dysplasia.

• Subject currently has a significant mechanical obstruction (stenosis).

• Subject has a current diagnosis of ulcerative or indeterminate colitis.

• Immunization with a live vaccine within 4 weeks of Screening, with the exception of influenza vaccine and no planned immunizations within the period of the study.

• Active or latent tuberculosis (TB) or tuberculosis infection; TB assessment and prophylaxis will be performed as per local biologicals regulations and guidelines.

• Subjects with a history of or ongoing chronic or recurrent infectious disease within the 12 months prior to Screening.

• Positive stool culture for Clostridium within the last 6 months prior to Screening.

• Use of prohibited medications/procedures, including;

• Concomitant corticosteroids doses exceeding 20 mg/day of prednisone (equivalent)

• Concomitant use of budesonide

• Concomitant use of anti-TNF therapy

• Subjects who received previous treatment with more than one anti-TNF agent

• Concomitant use of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil

• Prior or concomitant use of anti-a4 integrin or other non-TNF blocking biological

• Use of tube or enteral feeding, elemental diet, or parenteral alimentation started within 2 weeks prior to Screening

• Leukocytapheresis or granulocytapheresis within 2 weeks prior to Screening

• Use of any prescription medications/products (with the exception of prescription medications for contraception and/or medications deemed acceptable by the Investigator and Sponsor).

• Use of any over the counter (OTC), non-prescription preparations (including vitamins, minerals, phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to the Check-in visit (Day 0), unless deemed acceptable by the Investigator and Sponsor.

• Current or recent history (within 6 months of screening) of drug or substance abuse, including alcohol = 14 units per week or who have a significant history of alcoholism or drug/chemical abuse within 6 months prior to the Screening visit (one unit of alcohol equals 0.5 pint [285 mL] of beer or lager, one glass [125 mL] of wine, or 1 shot [25 mL] of spirits).

• Subjects with known clinically significant cardiac disease (e.g., myocardial infarction or stroke within 6 months prior to Screening, unstable angina, claudication, etc.), or evidence of a clinically significant electrocardiogram (ECG) abnormality at Screening.

• A history of significant neurologic, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary or metabolic disease within 30 days of the Screening visit, as judged by the Investigator.

• Have a family history (more than one first degree relative) of multiple thrombotic events or a personal history of any venous or arterial thrombotic event including deep vein thrombosis, stroke, myocardial infarction, pulmonary embolus, and peripheral arterial thromboembolic events.

• Subject has had a positive hepatitis panel (including hepatitis B surface antigen [HBsAg], hepatitis B core antibody, and hepatitis C virus antibody [anti-HCV]) or a positive HIV antibody screen at time of Screening.

• Evidence of hepatic dysfunction, viral hepatitis, or current or chronic history of liver disease including non-alcoholic steatohepatitis (NASH) or abnormal hepatic markers (AST, ALT, ALP, or total bilirubin > 1.5 x upper limit of normal) at the time of the Screening visit.

• Abnormal renal function (BUN or creatinine >1.25 x upper limit of normal) at the time of the Screening visit.

• White Blood Cells <4 x 103/mm3; platelets <150 x 103/mm, hemoglobin < 6.2 mmol/L at the time of the Screening visit.

• Subjects with evidence of other serious, significant, acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study.

• History of malignancy, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ.

• Active acute infection requiring systemic treatment for more than 2 weeks.

• Planned surgery during the study period or have undergone major surgery within the 3 months prior to the Screening visit.

• Subjects who have received any investigational drug within 60 days or use of other experimental anti-CD therapies within the last 30 days prior to Screening visit.

• Known sensitivity to any component of the study drug or previous sensitivity reaction or other clinically significant reaction to intravenous medications or biologic therapy.

• Subjects who have previously received FFP104 or have been previously enrolled in this study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• FFP104
Three intravenous infusions of FFP104 over 15 days (d0, d7 and d14)
• Placebo
Three intravenous infusions of 0.9% Saline over 15 days (d0, d7 and d14)

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Leuven	Leuven
Netherlands	Erasmus Medical Center	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Fast Forward Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability will be assessed through clinical laboratory tests, vital signs, physical exams, and adverse event assessments		Up to 84 days	Yes
Secondary	Proportion of subjects achieving clinical response (decrease of Crohn's Disease Activity Index (CDAI) score by =100 points from baseline)		Days 0, 7, 14, 28, 42 and 84	No
Secondary	Proportion of subjects achieving clinical remission (attainment of absolute CDAI score of 150 points or less from baseline)		Days 0, 7, 14, 28, 42 and 84	No
Secondary	Proportion of subjects achieving partial response (decrease of CDAI score by >70 points from baseline)		Days 0, 7, 14, 28, 42 and 84	No
Secondary	Difference in CDAI score between FFP104 treated subjects and placebo subjects in each arm of the study		Days 0, 7, 14, 28, 42 and 84	No
Secondary	Time to response (decrease in CDAI score by >100 points)		Days 0, 7, 14, 28, 42 and 84	No
Secondary	Time to partial response (decrease of CDAI score by >70 points)		Days 0, 7, 14, 28, 42 and 84	No
Secondary	Change from baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS)		Day 42	No
Secondary	Change from baseline in gut tissue organisation (histology)		Day 42	No
Secondary	Percent change from baseline in faecal calprotectin level		Day 42	No
Secondary	Percent change from baseline in C-Reactive Protein (CRP) levels		Day 7, 14, 28, 42 and 84	No
Secondary	Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ)		Day 42	No
Secondary	Change from baseline in health outcome measures	Health outcome measures that will be used are Short Form 36 (SF36), the EuroQol EQ-5D-5L and the Work Productivity and Activity Impairment Questionnaire Crohn's Disease (WPAI-CD)	Day 42	No
Secondary	To evaluate changes from baseline in serum FFP104 levels		up to 84 days	No
Secondary	To evaluate changes in lymphocyte sub-populations in peripheral blood		Day 0, 14 and 42	No