Clinical Study to Evaluation the Efficacy and Safety of PRV-6527 an Inhibitor of Colony Stimulating Factor-1 Receptor, in patients with Moderately to Severely Active Crohn’s Disease

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2017-003017-25-HU
• Date of registration: 13/11/2017
• Prospective Registration: Yes
• Primary sponsor: Provention Bio, Inc.
• Public title: Clinical Study to Evaluation the Efficacy and Safety of PRV-6527 an Inhibitor of Colony Stimulating Factor-1 Receptor, in patients with Moderately to Severely Active Crohn’s Disease
• Scientific title: A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Evaluate the Efficacy and Safety of Oral PRV-6527 (JNJ-40346527), an Inhibitor of Colony Stimulating Factor-1 Receptor, in Subjects with Moderately to Severely Active Crohn’s Disease - PRovention INvestigation in Crohn’s DiseasE (PRINCE)
• Date of first enrolment: 08/01/2018
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003017-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; 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

Austria, Germany, Hungary, Poland, Russian Federation, Spain, Ukraine

Contacts

• Name: project manager
• Affiliation: PSI Company Ltd

• Name: project manager
• Affiliation: PSI Company Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1.Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. All subjects must be capable of signing their own ICF and complete the eDiary.
2. Subject must be a man or woman between 18 years and 75 (inclusive) years of age.
3. Has moderate to severe CD with a CDAI score between 220 and 450 (inclusive) and a histologic diagnosis of CD for at least 3 months before screening.
4. Has screening laboratory test results within the following parameters:
a. Hemoglobin =8 g/dL
b. WBC =2000 cells/µL
c. Neutrophils =1500 cells/µL
d. Creatinine =1.7 mg/dL
e. Serum AST or ALT =2 x upper limit of normal (ULN)
f. Total bilirubin =2 x ULN
g. CPK =3 x ULN
h. LDH =3 x ULN
5.SES-CD score =6 or =4 for ileal-only disease
6. Subject may be either biologic naïve (30% to 40% of enrollment) or biologic experienced (60% to 70% enrollment). Subjects who have had prior experience with anti-TNF, anti-integrin, or anti-MAdCAM-1 treatment would be eligible if they were primary nonresponders, secondary nonresponders, intolerant to anti-TNF agents, or stopped such treatment for other reasons Subjects who have had prior experience with anti-IL-12/23 or anti-IL-23 agents would be eligible if they were responders, secondary nonresponders, or stopped the treatment due to intolerance or reasons unrelated to efficacy.
7. Female subjects must meet the following inclusion criteria:
a. Women not of childbearing potential:
Postmenopausal is defined as being >45 years of age with amenorrhea for at least 18 months) or >45 years of age with amenorrhea for at least 12 months and a serum follicle stimulating hormone (FSH) level >40 IU/L with luteinizing hormone (LH) level >40 IU/L; permanently sterilized (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy.
b. Women of childbearing potential:
1) Must have a negative serum ß-human chorionic gonadotropin (ß-hCG) at screening and a negative urine pregnancy test at Week 0 prior to dosing
2) Must practice a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: eg, established use (>3 months) of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject).
3).Must agree to use highly effective methods of birth control throughout the study for 3 months after receiving the last dose of study drug (placebo or PRV-6527).
4) Must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 3 months after receiving the last dose of study drug.
8. Male subjects must meet the following criterion: A man who is sexually active with a woman of childbearing potential and has not had
Exclusion criteria:
1. Has ileostomy, colostomy, or short gut syndrome or is anticipated to require surgery in the next 6 months.
2. Has untreated active external or perianal fistula or abscess.
3. Has other gastrointestinal inflammatory diseases.
4. Has any malignancy or lymphoproliferative disorder other than nonmelanoma cutaneous malignancies or cervical carcinoma
6. Is a primary nonresponder to anti-IL-12/23 or anti-IL-23 biologic treatment.
7. Has been previously treated with natalizumab.
8. Has been treated with tofacitinib, cyclosporine, or other immunosuppressives including biologics .
9. Has been on a variety of doses of thiopurines or MTX within 8 weeks of screening.
10. Has been treated with unstable doses of mesalamine or chronic antibiotics within 30 days before screening.
11. Has been treated with rectal steroids or systemic corticosteroids
12. Has been treated with proton pump inhibitors (PPIs) or cimetidine within 30 days before screening. NOTE: Subjects may take H2 receptor agonists other than cimetidine. Antacids may be used except within 2 hours of dosing.
13. Subject is receiving and/or is anticipated to require strong inhibitors or inducers of CYP3A4, CYP2C8, and CYP2C19 isoenzymes during the study Subject is receiving and/or is anticipated to require substrates of p-glycoprotein during the study,
15. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to endemic fungal infections, chronic renal infection, chronic chest infection, recurrent urinary tract infection, or a history of serious infection
16. Has current signs or symptoms of an acute infection or infected skin wounds or ulcers, with the exception of nonserious infections in the opinion of the Investigator
17. Has or ever has had a non-TB mycobacterial infection or serious opportunistic infection (eg, cytomegalovirus colitis, Pneumocystis carinii, aspergillosis).
18. Female subject is pregnant, lactating, planning to become pregnant, or sexually active of childbearing potential and refuses to use highly effective birth control. Male subject is planning on fathering a child.
19. Has received an investigational drug or used an invasive investigational medical device within 12 weeks before the planned first administration of study drug.
20. Has positive serology to human immunodeficiency virus (HIV) 1 or 2 confirmed by HIV RNA+, hepatitis C virus (HCV) [anti-HCV+ with HCV RNA+]; hepatitis B virus (HBV) [HBsAg+ or Total anti-HBc+ with HBV DNA+] at screening.
21. Has a stool culture or microscopic examination positive for enteric pathogens, ova, and parasites. Positive Clostridium difficile toxin or glutamate dehydrogenase (GDH) (C diff QUIK CHEK) with confirmatory positive polymerase chain reaction (PCR) at screening.
22. Subject is not eligible if he or she meets any of the following TB screening criteria:
a. Has a history of untreated latent or untreated active TB prior to screening.
b. Has signs or symptoms suggestive of active TB upon medical history and/or physical examination.
c. Has had recent close contact with a person with active

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

Health Condition(s) or Problem(s) studied

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

Moderately to severely Active Crohn's Disease
MedDRA version: 20.0 Level: LLT Classification code 10011402 Term: Crohn's disease (colon) System Organ Class: 100000004856
MedDRA version: 20.0 Level: LLT Classification code 10011403 Term: Crohn's disease aggravated System Organ Class: 100000004856
MedDRA version: 20.1 Level: LLT Classification code 10058815 Term: Crohn's disease acute episode System Organ Class: 100000004856

Intervention(s)

Product Name: JNJ-40346527-AAC
Product Code: PRV-6527(JNJ-40346527)
Pharmaceutical Form: Capsule, hard
CAS Number: 1142364-35-9
Current Sponsor code: PRV-6527(JNJ-40346527)
Other descriptive name: JNJ-40346527-AAC
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: The secondary objectives are to evaluate the effect of PRV-6527 for 12 weeks on:
Clinical
• Colonic and ileal mucosa, based upon the Simple Endoscopic Score for CD (SES-CD)
• Clinical symptoms, based upon the frequency of diarrheal stools and abdominal pain
• Clinical symptoms, based upon the PRO-2 portion of SES-CD
Safety
• Safety and tolerability of PRV-6527 in subjects with active CD
Pharmacokinetics (PK)
• Trough plasma concentrations of PRV-6527 and its active metabolites, M2 and M7, in subjects with active CD
Pharmacodynamics (PD)
• PD effects measured by fecal calprotectin (FC) and ultrasensitive C-reactive protein (CRP)

Main Objective: The primary objective is to evaluate the efficacy of PRV-6527 for 12 weeks in the treatment of moderately to severely active CD, as measured by the Crohn’s Disease Activity Index (CDAI).

Primary end point(s): The change in CDAI score

Timepoint(s) of evaluation of this end point: From baseline to Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12

Secondary end point(s): Clinical
• Change from baseline to Week 12 in SES-CD score
• Change from baseline to Week 12 in abdominal pain based on a Numerical Rating Scale (NRS) (0-10 scale)
• Change from baseline to Week 12 in the number of daily loose or watery stools (type 6 or 7 stools) per week, as defined by the Bristol Stool Form Scale (BSFS)
• Change from baseline to Week 12 in PRO-2 score
Safety
• Treatment Emergent Adverse Events (TEAEs), adverse events (AEs) leading to withdrawal and Serious Adverse Events (SAEs)
• Clinically significant changes in vital signs, electrocardiogram (ECG), and laboratory tests
PK
• Cmin of PRV-6527 and its active metabolites, M2 and M7
PD
• Change from baseline to Week 12 in ultrasensitive CRP
• Change from baseline to Week 12 in FC

Secondary ID(s)

PRV-6527-CD2a

Source(s) of Monetary Support

Provention Bio, Inc.

Ethics review

Status: Approved
Approval date:
Contact: