Drug OPRX-106 in Patients with Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2016-000509-35-BG
• Date of registration: 03/08/2016
• Prospective Registration: Yes
• Primary sponsor: Protalix Biotherapeutics Ltd.
• Public title: Drug OPRX-106 in Patients with Ulcerative Colitis
• Scientific title: An Open Label, Proof of Concept Study to Assess the Safety, PK and Explore Efficacy of OPRX-106 in Patients with Active Mild to Moderate Ulcerative Colitis
• Date of first enrolment: 27/10/2016
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000509-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Israel, Serbia

Contacts

• Name: AXIOM International BG
• Affiliation: AXIOM International BG

• Name: AXIOM International BG
• Affiliation: AXIOM International BG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males or females, 18 to 70 years of age inclusive
2. Have had a diagnosis of ulcerative colitis per European guideline criteria for a minimum of 3 months by:
a. medical history
b. physical examination
c. laboratory tests (anemia, increased levels of C-reactive protein(CRP), fecal samples for blood)
d. histopathological evidence from flexible sigmoidoscopy or colonoscopy
3. Have active mild to moderate ulcerative colitis, as defined by a full Mayo score at Screening. Full Mayo score of 4 to 9 (inclusive) will consist of:
a. Stool frequency (Mayo subscore =1);
b. Rectal bleeding (Mayo subscore =1);
c. Endoscopic evidence of active mucosal disease (i.e., Mucosal appearance, Mayo subscore =1), as assessed by flexible sigmoidoscopy unless colonoscopy is clinically indicated.
d. Physician’s Global Assessment (PGA) of at least mild disease (Mayo sub-score =1).
4. If female, not be of childbearing potential, as evidenced by being surgically sterile or postmenopausal for at least 12 months, or be using acceptable contraception methods such as hormonal contraception or two forms of barrier contraception. Acceptable contraception must be used consistently from 30 days before Screening Visit through study completion.
5. If male, not be of fathering potential, as evidenced by being surgically sterile for at least 12 months, or be using double barrier methods of contraception (e.g. use of condom AND an acceptable contraception method by the female partner such as hormonal contraception).
6. If female, have a negative serum pregnancy test at Screening Visit and a negative urine pregnancy test at Baseline before administration of study treatment.
7. Be willing and able to adhere to the study visit schedule and other protocol requirements.
8. Be willing and able to provide voluntary written informed consent.
9. Have adequate cardiac, renal and hepatic functions as determined by the investigator and demonstrated by screening clinical and laboratory evaluations and physical examination results; these findings must all be within normal limits or judged not clinically significant by the investigator.
10. High level of calprotectin (>100 mg/kg of stool)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Have a history of colonic or rectal surgery other than hemorrhoidal surgery or appendectomy
2. Currently receiving total parenteral nutrition (TPN)
3. Positive for active / latent mycobacterium tuberculosis (TB) infection at the Screening Visit
4. Positive laboratory tests for HIV, HBs-Ag and HCV at the Screening Visit
5. Pregnant or breast-feeding, or plan to become pregnant during the study
6. Have a history of infection requiring administration of any IV antibiotic, antiviral or antifungal medication within 30 days of Screening Visit throughout study completion or any oral antiinfective agent within 14 days of Screening Visit or at any time during the study
7. Severe ulcerative colitis evidenced by the following signs of toxicity: heart rate >90 beats/min at rest, temperature >38.0°C
8. Ulcerative proctitis, defined as disease limited to less than 15 cm from the anal verge
9. Use a vaccine or other immunostimulator within 4 weeks prior to Screening Visit or any time during the study
10. Use >4.8 g 5-ASA or equivalent within 2 weeks prior to the Screening Visit or at any time during the study.
a. Use of 5-ASA or equivalent=4.8 g is allowed if the dose during the 2 weeks prior to the Screening Visit was stable, subject is to remain on stable dose through End of Study Visit (Week 10, Visit 7)
11. Use of corticosteroid or 5-ASA enemas, foams, or suppositories within two weeks prior to the Screening Visit or at any time during the study.
12. Use of anti-inflammatory medications (cromones, xanthines, leukotriene antagonists) or natural remedies (Probiotics, omega-3 fatty acids) within 4 weeks prior to ScreeningVisit or any time during the study
13. Use of oral or parenteral antibiotics within two weeks prior to the Screening Visit or at any time during the study.
14. Use of chronic non-steroidal anti-inflammatory (NSAID) therapy
a. Occasional use of NSAIDs and acetaminophen for headache, arthiritis, myalgias, menstrual cramps etc., as well as daily use of low-low dose (81-162 mg) aspirin for cardiovascular prophylaxis is permitted
15. Use of immune suppressive agents including anti-TNF agents, Azathioprine, 6MP, Methotrexate 12 weeks prior to Screening Visit or at any time during the study.
16. Use of steroids 12 weeks prior to Screening Visit or at any time during the study.
17. Have a diagnosis of:
a. Crohn’s disease;
b. Indeterminate colitis (inability to distinguish between ulcerative colitis and Crohn’s
disease);
c. Microscopic colitis (collagenous or lymphocytic colitis);
d. Ischemic or infectious colitis;
e. Clostridium difficile colitis at Screening Visitor within 90 days of the Screening Visit;
f. Parasitic disease within 90 days of the Screening Visit
18. Have a congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ transplantation)
19. Have clinically significant abnormal laboratory test results, unless regarded by the investigator as related to ulcerative colitis:
a. Hemoglobin level <10.5g/dL
b. White blood cell count < 3 x 103/µL
c. Lymphocyte count < 0.5 x 103/µL
d. Platelet count < 100 x 103/µL or > 1200 x 103/µL
e. Alanine aminotranseferase (ALT) or apartate aminotransferase (AST) > 3 x the upper limit of normal (ULN)
f. Alkaline phosphatase >3 x ULN
g. Serum creatinine > 2 x ULN
20. Active abuse of alcohol or illicit drugs.
21. Have a known malignancy or history of malignancy that would reduce life expectancy.
22. Have any condition, which in the opinion of the investigator, would place

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Active mild to moderate ulcerative colitis

Intervention(s)

Product Name: OPRX-106 (plant cells expressing TNFR-Fc) 8mg
Product Code: OPRX-106
Pharmaceutical Form: Powder for oral suspension

Product Name: OPRX-106 (plant cells expressing TNFR-Fc) 2mg
Product Code: OPRX-106
Pharmaceutical Form: Powder for oral suspension

Primary Outcome(s)

Main Objective: To evaluate the safety, pharmacokinetics, and explore efficacy of two dose arms of OPRX-106 administered orally, once daily for 8 weeks to subjects with active mild to moderate ulcerative colitis.

Primary end point(s): PHARMACOKINETIC ENDPOINT
SAFETY ENDPOINT

Timepoint(s) of evaluation of this end point: PHARMACOKINETIC ENDPOINT:
OPRX-106 individual plasma levels (PK) in subjects with active mild to moderate Ulcerative Colitis following single and multiple dose administration of OPRX-106.
Baseline - pre dose and 1, 2 4 and 6 hours
End of Treatment Visit (Week 8, Visit 6) - pre dose and 1, 2 4 and 6 hours
SAFETY ENDPOINT:
Safety will be assessed by spontaneously reported adverse events and changes from Baseline in physical examination findings, vital signs, ECGs, concomitant medications, anti OPRX-106 antibodies, and laboratory test results

Secondary Objective: Safety Objective:
- To evaluate the safety of OPRX 106 (2 mg and 8 mg) administered orally, once daily, for 8 weeks to subjects with active mild to moderate ulcerative colitis.
Pharmacokinetic Objective:
- To evaluate the pharmacokinetics of OPRX-106 (2 mg and 8 mg) following single and multiple dose administration
Exploratory Objectives:
- To explore efficacy of OPRX-106 (2 mg and 8 mg) administered orally, once daily, for 8 weeks to subjects with active mild to moderate ulcerative colitis.
- To evaluate exploratory parameters related to immune-modulation effect of OPRX-106 (2 mg and 8 mg) administered orally, once daily, for 8 weeks to subjects with active mild to moderate ulcerative colitis.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: EXPLORATORY EFFICACY ENDPOINTS:
1. Clinical response (improvement) at Baseline vs. Week 8 (Visit 6)
2. Histopathological improvement in Geboes histological grading from Baseline to Week 8 (Visit 6).
3. Improvement in hs-CRP levels from Baseline to Week 8 (Visit 6).
4. Improvement in fecal calprotectin levelsfrom Baseline to Week 8 (Visit 6).
5. Changes in the composition of the intestinal microbiome from Baseline to Week 8 (Visit 6), if applicable,
6. Change in systemic immune modulation parameters from Baseline to Week 8 (Visit 6).
7. Change in gut tissue immune modulation parameters from Baseline to Week 8 (Visit 6).

Secondary end point(s): EXPLORATORY EFFICACY ENDPOINTS

Secondary ID(s)

PB-106-003

Source(s) of Monetary Support

Protalix Biotherapeutics Ltd.