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
Conditions
Interventions
Product Name: JNJ-40346527-AAC
Product Code: PRV-6527 (JNJ-40346527)
Pharmaceutical Form: Capsule, hard
CAS Number: 1142364-35-9
Current
Sponsors
Provention Bio, Inc.
Eligibility
Sex/Gender
All
Inclusion 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. The histological diagnosis should be confirmed locally from the screening colonoscopy if not previously documented at the site. 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 or biologic experienced. 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 or allergic to anti-TNF agents (e.g. infliximab), or stopped such treatment for other reasons Subjects who have had prior experience with anti-IL-12/23 (e.g. ustekinumab)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. Primary nonresponders to anti-IL-12/23 or anti-23 are excluded (see exclusion #6). 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 confirmatory serum follicle stimulating hormone (FSH) level >40 IU/L with luteinizing hormone (LH) level >40 IU/L in woman not receiving hormone replacement therapy; permanently sterilized (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy. Note: tubal ligation is not considered permanent sterilization. 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 ( 3 months) of oral, injected or implanted highly effective 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
Exclusion criteria
Exclusion criteria: 1.Ileostomy, colostomy, or short gut syndrome or is anticipated to require surgery in the next 6 months, or has tight stricture that prevents the passage of any colonoscope. 2.Untreated active external or perianal fistula or abscess. 3.Other gastrointestinal inflammatory diseases. 4.Any malignancy or lymphoproliferative disorder other than nonmelanoma cutaneous malignancies or cervical carcinoma 5.Colon cancer or severe dysplasia. Subjects with CD for =8 years involving the colon are not excluded if they had a colonoscopy to assess for the presence of dysplasia w/in 1 year before baseline or if they had a colonoscopy at the scr. (Any polyps revealed during the scr. endoscopy should be appr evaluated and removed. Larger polyps >1 cm should be fully resected and histologically evaluated) 6.Is a primary nonresponder to anti-IL-12/23 or anti-IL-23 biologic tx 7.Prev treatment w/natalizumab 8.Treatment w/tofacitinib, cyclosporine, or other immunosuppressives incl biologics w/in 5 half-lives before randomization. A serum concentration level below the limit of quantitation is acceptable 9.Has been on a variety of doses of thiopurines or MTX w/in 8 wks of scr 10.Treatment w/unstable doses of mesalamine (5-ASA) or chronic antibiotics within 30 days before scr 11.Treatment w/oral prednisone or prednisolone >20 mg or budesonide >6 mg per day, or other corticosteroids of equivalent doses, w/in 2 wks of scr. Doses of steroids must remain stable from at least 2wks prior to scr to wk12. Tx w/rectal steroids or systemic corticosteroids (IV os IM) is prohibited throughout the study except for the tx of AE 12.Treatment w/proton pump inhibitors (PPIs) or cimetidine within 7 days before baseline. Subjs may take non-cimetidine H2 receptor agonists incl. high doses for RGRD. Antacids may be used except w/in 2 hrs of dosing 13.Subj is receiving and/or is anticipated to require strong inhibitors or inducers of CYP3A4, CYP2C8, and CYP2C19 isoenzymes 14. Subj is receiving and/or is anticipated to require substrates of pglycoprotein during the study 15.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.Acute infection or infected skin wounds or ulcers, w/the exception of nonserious infections in the opinion of the PI 17.Non-TB mycobacterial infection or serious opportunistic infection 18.Female subj is pregnant, lactating, planning to become pregnant, or sexually active of childbearing potential and refuses to use highly effective birth control. Male subj is planning on fathering a child during and w/in 3 mos after study tx 19.Has received an investigational drug or used an invasive investigational medical device within 12 wks before the planned 1st administration of IP 20.Has antibody to p24 antigen for HIV 1 or 2 confirmed by Western blot, hepatitis C virus at scr, [anti-HCV+ w/HCV RNA+]; hepatitis B Virus (HBV) [HBsAg+ or Total anti-HBc+ w/HBV DNA+] 21.Has a stool culture or microscopic exam pos for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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; 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 CDAI 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 and their sum, in subjects with active CD Pharmacodynamics (PD) • PD effects measured by fecal calprotectin (FC) and ultrasensitive C-reactive protein (CRP) ;Timepoint(s) of evaluation of this end point: From baseline to Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 and their sum PD • Change from baseline to Week 12 in ultrasensitive CRP • Change from baseline to Week 12 in FC | — |
Countries
Austria, Germany, Hungary, Poland, Russian Federation, Spain, Ukraine
Contacts
Public Contactproject manager
PSI Company Ltd
Outcome results
None listed