Clinical Study to Evaluate 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
- Conditions
- Moderately to Severely Active Crohn's DiseaseMedDRA version: 20.0Level: LLTClassification code 10011402Term: Crohn's disease (colon)System Organ Class: 100000004856MedDRA version: 22.1Level: LLTClassification code 10011403Term: Crohn's disease aggravatedSystem Organ Class: 100000004856MedDRA version: 20.1Level: LLTClassification code 10058815Term: Crohn's disease acute episodeSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2017-003017-25-PL
- Lead Sponsor
- Provention Bio, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
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 women
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 (<1% failure rate) consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies such as established use (>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 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
1. Has ileostomy, colostomy, or short gut syndrome; is anticipated to require surgery in the next 6 mos, or has tight stricture that prevents the passage of any colonoscope.
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.
5. Has colon cancer or severe dysplasia.
6. Is a primary nonresponder to anti-IL-12/23 or anti-IL-23 biologic tx.
7. Has been prev treated w/natalizumab.
8. Has been treated w/tofacitinib, cyclosporine, or other immunosuppressives (including biologics).
9. Has been on a variety of doses of thiopurines or MTX w/in 8 wks of scr.
10. Has been treated w/unstable doses of mesalamine (5-ASA) or chronic antibiotics within 30 days before scr.
11. Has been treated w/oral prednisone or prednisolone >20 mg or budesonide >6 mg per day, or other corticosteroids of equivalent doses, within 2 wks of screening. Note: Doses of steroids must remain stable from at least 2 wks 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. Has been treated w/proton pump inhibitors (PPIs) or cimetidine within 7 days before baseline (randomization). NOTE: Subjs may take non-cimetidine H2 receptor agonists including 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 during the study.
14. Subj 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, w/the exception of nonserious infections in the opinion of the PI.
17. Has or ever has had a non-TB mycobacterial infection or serious opportunistic infection (eg, cytomegalovirus colitis, Pneumocystis carinii, aspergillosis).
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 study drug.
20. Has positive antibody to p24 antigen (Ab-p24Ag) for HIV 1 or 2 confirmed by HIV 1/2 Western blot, hepatitis C virus (HCV) [anti-HCV+ w/HCV RNA+]; hepatitis B virus (HBV) [HBsAg+ or Total anti-HBc+ w/HBV DNA+] at scr.
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) w/confirmatory positive polymerase chain reaction (PCR) at scr.
22. Subj meets any of the following TB scr criteria:
a. Has a hist of untreated latent or untreated active TB prior to scr.
b. Has signs or symptoms suggestive of active TB upon medical history and/or physical examination.
c. Has had recent close contact w/a person w/active TB and has not been e
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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).;Secondary Objective: The secondary objectives are to evaluate the effect of PRV-6527 for 12 weeks on:<br>Clinical<br>• Colonic and ileal mucosa, based upon the Simple Endoscopic Score for CD (SES-CD)<br>• Clinical symptoms, based upon the frequency of diarrheal stools and abdominal pain<br>• Clinical symptoms, based upon the PRO-2 portion of CDAI<br>Safety<br>• Safety and tolerability of PRV-6527 in subjects with active CD<br>Pharmacokinetics (PK)<br>• Trough plasma concentrations of PRV-6527 and its active metabolites, M2 and M7 and their sum, in subjects with active CD<br>Pharmacodynamics (PD)<br>• PD effects measured by fecal calprotectin (FC) and ultrasensitive C-reactive protein (CRP);Primary end point(s): The change in CDAI score;Timepoint(s) of evaluation of this end point: From baseline to Week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Clinical<br>• Change from baseline to Week 12 in SES-CD score<br>• Change from baseline to Week 12 in abdominal pain based on a Numerical Rating Scale (NRS) (0-10 scale)<br>• 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)<br>• Change from baseline to Week 12 in PRO-2 score<br>Safety<br>• Treatment Emergent Adverse Events (TEAEs), adverse events (AEs) leading to withdrawal and Serious Adverse Events (SAEs)<br>• Clinically significant changes in vital signs, electrocardiogram (ECG), and laboratory tests<br>PK<br>• Cmin of PRV-6527 and its active metabolites, M2 and M7 and their sum<br>PD<br>• Change from baseline to Week 12 in ultrasensitive CRP<br>• Change from baseline to Week 12 in FC;Timepoint(s) of evaluation of this end point: Week 12