Phase 2a To Evaluate PL-8177 in Subjects With Active Ulcerative Colitis (UC)

• Status: Not yet recruiting
• Trial end date: 2023-06-16
• Target enrollment: 0
• Participant gender: All

Summary

PL8177 will be given orally once daily to adult ulcerative colitis patients. Patients meeting eligibility criteria will be randomized to receive either PL8177 or placebo (3:1) for a treatment period of 8 weeks followed by a 4-week post-treatment period.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Palatin Technologies, Inc

Criteria

Inclusion Criteria:

• Age ≥18 to ≤75 years of age at Screening.

• Has a history of UC diagnosis at least 6 months prior to screening.

• Has active UC defined as a modified Mayo Endoscopic Subscore ≥2 during screening sigmoidoscopy, and fecal calprotectin > 250 mcg/g.

• Has evidence of endoscopic disease extending to at least 5 cm proximal to the anal verge, and minimum involvement of at least 50% of the macroscopically most affected colonic segment, i.e., in case of proctitis at least 50% of the rectum must be involved, in case of left-sided colitis at least 50% of the rectum or the sigmoid colon must be involved, etc. This will be confirmed by a central reader.

• Demonstrated intolerance, lack of response or inadequate response to aminosalicylates, and naïve to anti-TNF or other biologic, and/or small molecule therapies. If currently receiving 5-ASA, the duration and dose prior to the screening endoscopy must be as specified below, and a stable dose must be maintained throughout the double-blind trial:

o 5-aminosalicylates (5-ASA) (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide) for ≥4 weeks with the dose stable for ≥3 weeks prior to the screening endoscopy.

• If recently has received any of the following treatments, they must have discontinued as specified below:

• If 5-ASA has been recently discontinued, it must have been stopped for ≥3 weeks prior to the screening endoscopy.

• If a thiopurine has recently been discontinued, it must have been stopped for ≥4 weeks prior to the screening endoscopy.

• Oral corticosteroids must have been stopped for ≥4 weeks prior to the screening endoscopy.

• Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day 1 prior to first dose of study drug.

• Male and female patients of childbearing potential must agree to use 1 highly effective form of birth control during study participation and for 30 days after the last dose of study drug, unless the patient or his/her partner is surgically sterilized, or the patient agrees to abstain from sexual intercourse.

• Highly effective methods of birth control in this study include intrauterine device, hormonal contraceptives (oral, patch, long acting injectable, implant).

• Postmenopausal is defined as lack of menses for ≥12 months prior to screening, confirmed by serum FSH >25 IU at Screening.

• Has provided informed consent prior to initiation of any study specific activities/procedures.

• Understands and is willing and able to comply with study requirements, including the schedule of events and follow-up visits.

Exclusion Criteria:

• Any condition, physical finding, laboratory or ECG abnormality, which, in the opinion of the Investigator, poses a safety risk, will prevent the patient from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the patient.

• Has fulminant colitis, toxic megacolon, microscopic colitis, history of colitis-associated colonic dysplasia, active peptic ulcer disease, cervical dysplasia, or primary sclerosing cholangitis.

• History of Crohn's disease or indeterminate colitis, or the presence or history of a fistula consistent with Crohn's disease.

• Presence of ileostomy or colostomy, or history of prior colon resection.

• Presence of adenomatous colonic polyps that have not been removed.

• Stools positive for C. difficile, enteric pathogens (Salmonella, Shigella, Campylobacter), or ova and parasites within 28 days of screening. Screen failures due to positive C. difficile or other enteric infection can be re-screened after appropriate treatment.

• History of mitochondrial disorder.

• History of bleeding disorder (eg, complement deficiency, hemophilia, history of uncontrolled bleeding).

• History of primary or secondary immunodeficiency.

• History of cancer within the 5 years prior to screening including solid tumors and hematological malignancies (exception: no approval needed for basal cell and in situ squamous cell carcinomas of the skin that have been adequately treated with no re-occurrence for at least 1 year prior to screening).

• History of one or more clinically relevant neurologic, psychologic, ophthalmologic, pulmonary, cardiovascular, gastrointestinal (other than the UC), hepatic, renal, endocrine, or other major systemic disease of moderate (or worse) severity, making implementation of the protocol or interpretation of the study difficult. Examples of (but not limited to) conditions to be excluded, are the following:

• Uncontrolled hypertension, with systolic blood pressure (SBP) ≥160 mmHg, diastolic blood pressure (DBP) ≥90 mmHg.

• Uncontrolled hyperlipidemia (even if therapy is ongoing, LDL>160 mg/dl or triglycerides >500 mg/dL).

• Uncontrolled hyperthyroidism or hypothyroidism.

• Impaired hepatic function (Aspartate aminotransferase [AST] or Alanine aminotransferase [ALT] values >2.0 times the upper limit of the reference range and/or serum bilirubin >1.5 times the upper limit of the reference range at the screening visit).

• Cardiac or pulmonary disease, such as unstable angina or myocardial infarction within the past 12 months, congestive heart failure (CHF) Grade 2, 3, or 4 according to New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, or chronic pulmonary disease requiring oxygen, venous thrombosis.

• Stroke or transient ischemic attack (TIA) in the 12 months before screening.

• Major depressive illness in the last 3 years; any history of severe psychiatric illness (eg, schizophrenia).

• Multiple sclerosis or any other demyelinating disease.

• Any of the following laboratory abnormalities:

• Hemoglobin <8.5 g/dl (international system units [SI]: <85 g/L).

• Neutrophils <1500/mm3 (SI: < 1.5 x 109/L).

• White blood cell (WBC) count <3,000/mm3 (SI: < 3.0 x 109/L).

• Platelets <80,000 mm3 (SI: 80 x 109/L).

• International normalized ratio (INR) >1.5.

• Serum creatinine >1.5 x the upper limit of normal.

• Has a current bacterial, parasitic, fungal, viral, or mycobacterial infection, or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks prior to the screening visit, and/or oral antibiotics within 2 weeks prior to screening visit and at any time during the screening period.

• Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C (HCVAb) at Screening (note: HCV patients with undetectable viral load will be eligible).

• Clinically significant findings on 12-lead ECG such as, but not limited to, 2nd or 3rd degree AV block, prolongation of QRS complex over 120 msec, or QTcF interval ≥450 msec for males and ≥470 msec for females.