Phase 2a to Evaluate PL-8177 in Subjects with Active Ulcerative Colitis (UC) (PL8177-205)

Phase 2a, Double-Blind, Randomized Adaptive Design, Placebo-Controlled, Parallel Group Study to Evaluate the Safety, Tolerability, Efficacy, PK and Biomarkers with Oral Colon Delivery PL8177 in Adult Subjects with Active Ulcerative Colitis

The purpose of this study is to compare PL8177 (a melanocortin receptor agonist) to placebo (in a 3:1 ratio-meaning that for every 3 people that get the active drug, one will receive placebo). The study treatment will be for 8 weeks. The study will measure safety and the body's ability to handle PL8177 and look at the improvement and healing of the intestine after 8 weeks of treatment. The study will include adult males and nonpregnant, nonlactating females with acute Ulcerative Colitis (UC).

Study Overview

• Status: Active, not recruiting
• Conditions: Ulcerative Colitis; Ulcerative Colitis Flare; Ulcerative Colitis Acute; Ulcerative
• Intervention / Treatment: Drug: PL8177; Drug: PL8177 Placebo

Detailed Description

This study will have potential subjects participating for approximately 4 months: Subjects will be screened to assess their eligibility within 28 days prior to the first dose administration; Day 1 will be eligibility confirmation and in-clinic dosing; additional visits to occur at Weeks 2, 4, 8 and 12. Routine laboratory tests, vital signs and ECG will be measured as well as blood, stool and tissue samples obtained for biomarker and PK studies. Endoscopy is required at screening visit and week 8 visit. Patients will also be given an electronic diary to enter on a daily basis for the duration of their participation. Additional patient questionnaires will be done at clinic visits. Optional genomics testing will also be completed for this study to help look at genes and their effect on inflammation.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Del Sol Research Management, LLC
  • California
    • Lancaster, California, United States, 93534
      • Gastro Care Institute
    • Tarzana, California, United States, 91356
      • Valiance Clinical Research
  • Florida
    • Coral Springs, Florida, United States, 33067
      • Advanced Research LLC
    • Kissimmee, Florida, United States, 34741
      • IHS Health Research/Gastro Health
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc.
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Kansas Gastroenterology
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Gastroenterology Clinic of Acadiana
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Allied Health Clinical Research Organization, LLC - Englewood
    • Freehold, New Jersey, United States, 07728
      • Allied Digestive Health LLC
    • Jackson, New Jersey, United States, 08527
      • Allied Health Clinical Research Organization, LLC
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine - Jill Roberts Center for Inflammatory Bowel Disease
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-2582
      • UPMC Presbyterian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 to ≤75 years of age at Screening.
• Has a history of UC diagnosis prior to screening; confirmed by endoscopic and histologic evidence in the subject chart. If the historical evidence is not available, then endoscopic and histologic evidence can be confirmed during the screening period.

Note: If no complete colonoscopy (adequate in quality to assess for dysplasia and colorectal polyps) has been performed and documented (with reports) within the past 1 year as recommended by local and national guidelines depending on Colorectal cancer risk factors in the specified subject, a full colonoscopy should be performed at screening. If such results are available within one year, a flexible sigmoidoscopy with examination up to the splenic flexure will be used for screening.

• Has active UC defined as a MES ≥2 during screening sigmoidoscopy.
• Has evidence of endoscopic disease extending to at least 5 cm proximal to the anal verge.
• 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: 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 subjects 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 subject or his/her partner is surgically sterilized, or the subject 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). Note: Oral hormonal contraceptives should be combined estrogen and progesterone. If a progesterone-only oral contraceptive is used, then a second method of birth control should be used as well.
• 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:

Subjects will be excluded from the study if they meet any of the following criteria at the Screening visit unless otherwise stated:

• Any condition, physical finding, laboratory or ECG abnormality, which, in the opinion of the Investigator, poses a safety risk, will prevent the subject from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the subject.
• 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 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>200 mg/dl or triglycerides >500 mg/dL).
• Known 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 subjects 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.

Medications of exclusion:

• Non-steroidal anti-inflammatory drugs (NSAIDs) daily.
• Subjects on anti-coagulation therapy within 28 days prior to screening and through Day 56.

Note: (A daily dose of ASA 81mg, taken for cardio prophylaxis, is considered acceptable to be continued during the study.)

• Topical (i.e., enema or suppository) mesalamine or steroid within 14 days prior to screening endoscopy.
• Azathioprine, 6-mercaptopurine, or methotrexate within the 28 days prior to screening.
• Any prior use of mycohphenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide
• Any prior use of biologics: rituximab, efalizumab, anti-integrines (natalizumab, vedolizumab, etrolizumab), TNF antagonists (infliximab, , golimumab, certolizumab pegol), anti-IL-12/23 (ustekinumab, guselkumab, risankizumab, or mirikizumab) ≤ 3 months prior to first dosing or ≤ 5 elimination half-lives prior to first dosing (whichever is shorter).
• Any prior use of small molecules: JAK inhibitors (tofacitinib, baricitinib, upadacitinib, or other) or S1P receptor modulator (fingolimod, ozanimod, etrasimod) ≤ 3 months prior to first dosing or ≤ 5 elimination half-lives prior to first dosing (whichever is shorter).
• Use of PPI (proton pump inhibitor) during the study (Should be discontinued 72 hours prior to Day 1).
• Use of prescription medications started or with a dose adjustment within 4 weeks prior to study screening, or over-the-counter medications or supplements started or with a dose adjustment within 2 weeks prior to study screening. Medications under Inclusion Criterion #5 are not included. Short-term administration of drugs for acute conditions are acceptable.
• Anti-diarrheal medications are not allowed within 48 hours of screening and throughout the study.
• Participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to screening or is currently participating in another trial of an investigational drug (or medical device).
• Subjects with planned hospitalization or surgery during the study.
• Subject has known sensitivity to any of the products or components to be administered during dosing.
• Has previously received PL8177.
• History of alcohol or drug abuse and/or positive drug test at screening (with exception of marijuana if legal within the state and no drug abuse is noted in the PI's assessment)
• Positive TB or COVID 19 test. Note: Patients with positive TB results who had active or latent TB in the two years preceding the screening visit and who were treated for TB can participate in study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PL8177; PL8177 will be given orally and daily from baseline until end of study.	Drug: PL8177; Approximately 3/4 of randomized patients will receive active PL8177.; Other Names: Active study medication
Placebo Comparator: Placebo; Approximately 1/4 of randomized patients will receive matching placebo as means of comparison to active treatment PL8177.	Drug: PL8177 Placebo; Approximately 1/4 of randomized patients will receive matching placebo as means of comparison to active treatment PL8177.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the proportion of subjects achieving Mayo Endoscopic Subscore of ≤ 1 point (0 or 1) between PL8177 and placebo after 8 weeks of treatment.	Efficacy will be determined through the use of the Mayo Endoscopic Subscore.	Time Frame: Mayo Endoscopic Subscore will be evaluated at Week 8.
To evaluate the safety and tolerability of PL8177 compared to placebo in patients with active UC.	Adverse events (AEs) will be collected from the time of signing the informed consent form (ICF). All subjects who are randomized will be monitored for AEs until the time they leave the study.	Baseline through Study Completion (Week 12).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summarize and evaluate the efficacy of PL8177 compared to placebo on histologic-endoscopic mucosal improvement	Summarize and evaluate the efficacy of PL8177 compared to placebo on histologic-endoscopic mucosal improvement (HEMI) after 8 weeks of treatment. Histologic-Endoscopic Mucosal Improvement is defined as MES of ≤ 1 point and a Geboes score ≤ 3.1.	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo on endoscopic remission	Summarize and evaluate the efficacy of PL8177 compared to placebo on endoscopic remission defined as MES = 0	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo on histologic remission	Summarize and evaluate the efficacy of PL8177 compared to placebo on histologic remission after 8 weeks of treatment (Geboes score ≤ 3.1)	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the Ulcerative Colitis Endoscopic Index of Severity	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) after 8 weeks of treatment.	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the change in sum scores of segmental endoscopic disease severity for both the segmental MES and segmental UCEIS	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the change in sum scores of segmental endoscopic disease severity for both the segmental MES and segmental UCEIS (rectum, sigmoid colon, descending colon) from baseline to Week 8.	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the fecal calprotectin levels	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the fecal calprotectin levels between baseline and Day 56/Week 8	Baseline through Week 8 (Day 57)
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the Stool Frequency Subscore	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the Stool Frequency Subscore (SFS) after 8 weeks of treatment	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the Rectal Bleeding Subscore	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the Rectal Bleeding Subscore (RBS) after 8 weeks of treatment	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the 32-item Inflammatory Bowel Disease Questionnaire	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ- 32) questionnaire after 8 weeks of treatment	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the Patient Reported Outcome	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the Patient Reported Outcome (PRO-2) after 8 weeks of treatment.	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the proportion of patients that have a clinical response	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the proportion of patients that have a clinical response defined as a reduction from baseline in the 3-component Mayo score of ≥ 2 points and ≥ 30% reduction from baseline with an accompanying decrease in RBS of ≥ 1 point or absolute RBS of ≤ 1 point.	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the proportion of patients that achieve clinical remission	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the proportion of patients that achieve clinical remission defined as a 3-component Mayo score of ≤ 2 with SFS = 0 or 1; RBS = 0; Centrally read endoscopy subscore = 0 or 1 (score of 1 modified to exclude friability) after 8 weeks of treatment.	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the intra-subject change in rectosigmoid disease	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the intra-subject change in rectosigmoid disease (per the MES) after 8 weeks of treatment	Baseline through Week 8
Summarize and evaluate the efficacy of PL8177 compared to placebo based on the overall global improvement	Summarize and evaluate the efficacy of PL8177 compared to placebo based on the overall global improvement across efficacy parameters, summing the number of efficacy endpoints that improved	Baseline through Week 8

Collaborators and Investigators

• Sponsor: Palatin Technologies, Inc
• Investigators: Study Director: Robert Jordan, VP Clinical Operations, Telephone: 609-598-1786; Email: rjordan@palatin.com

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2022
• Primary Completion (Actual): February 10, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Ulcerative Colitis
• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Ulcer
• Other Study ID Numbers: PL8177-205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No