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A Study Evaluating the Efficacy and Safety of ST-0529 in Subjects With Moderately to Severely Active Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT03844932
Recruitment Status : Recruiting
First Posted : February 19, 2019
Last Update Posted : June 10, 2019
Sponsor:
Collaborator:
Dr. Falk Pharma GmbH
Information provided by (Responsible Party):
Sublimity Therapeutics Holdco Limited

Brief Summary:
Study CYC-202 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of ST-0529 in subjects with moderately to severely active UC, defined as a score of 5 to 9 on the 3-Component Adapted Mayo Score (comprised of rectal bleeding, stool frequency and endoscopy sub-scores; score range 0-9).

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: ST-0529 Phase 2

Detailed Description:

The study consists of a Screening period, Treatment period and Follow-up. The Screening period is comprised of two separate in-clinic visits, SV1 and SV2. At the initial Screening visit (SV1), subjects will be required to provide written informed consent to participate in the study and will then be assessed for eligibility. Electronic diaries will be provided to subjects at this visit to use for the duration of the study in order to record information relating to their UC disease. Subjects will return to the clinic for their Screening endoscopic assessment (SV2). Ulcerative colitis disease activity for eligibility will be assessed using the 3-Component Adapted Mayo Score. Upon successful completion of the Screening period, subjects will return to the clinic for their Baseline visit.

During the Treatment period, subjects will be evaluated in the clinic at Baseline (Day 1), Week 2, Week 4, Week 8, and Week 12 (End of Treatment Period). At Week 6 and Week 10, subjects will be contacted by telephone to assess Adverse Events (AEs), concomitant medication usage and study drug regimen adherence.

Subjects who complete the 12-week Treatment period will attend the Week 16 End of Study (EOS) visit. Subjects who discontinue study drug and withdraw or are withdrawn from the study before the Week 12 visit will be requested to return to the clinic as soon as possible to complete an Early Termination (ET) visit.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study will investigate ST-0529 doses of 18.75 mg BID, 37.5 mg BID, or 75 mg BID, versus matching placebo BID.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: The study will be conducted as a double-blind study. Both the Investigator and subjects will be blinded with respect to the treatment the subject will receive. In addition, the central reader of the endoscopy assessment will be blinded to subject treatment for the entire study.
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of ST-0529 in Subjects With Moderately to Severely Active Ulcerative Colitis
Actual Study Start Date : January 24, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ST-0529 18.75 mg
ST-0529: 18.75 mg orally twice daily (BID)
Drug: ST-0529
ST-0529 utilizes SmPill® technology to encapsulate the otherwise insoluble cyclosporine in a presolubilized, lipid-based formulation.
Other Name: cyclosporine

Experimental: ST-0529 37.5 mg
ST-0529: 37.5 mg orally twice daily (BID)
Drug: ST-0529
ST-0529 utilizes SmPill® technology to encapsulate the otherwise insoluble cyclosporine in a presolubilized, lipid-based formulation.
Other Name: cyclosporine

Experimental: ST-0529 75 mg
ST-0529: 75 mg orally twice daily (BID)
Drug: ST-0529
ST-0529 utilizes SmPill® technology to encapsulate the otherwise insoluble cyclosporine in a presolubilized, lipid-based formulation.
Other Name: cyclosporine

Placebo Comparator: Matching Placebo
Placebo: matching placebo orally twice daily (BID)
Drug: ST-0529
ST-0529 utilizes SmPill® technology to encapsulate the otherwise insoluble cyclosporine in a presolubilized, lipid-based formulation.
Other Name: cyclosporine




Primary Outcome Measures :
  1. Clinical Remission at Week 12 [ Time Frame: Week 12 ]

    Stool frequency sub-score of ≤ 1 associated with a decrease ≥ 1 point from baseline, rectal bleeding sub-score of 0, and an endoscopic sub-score of ≤ 1 using the 3-Component Adapted Mayo Score.

    The 3-Component Adapted Mayo Score is a measure of UC disease ranging from 0 to 9 points and consists of 3 sub-scores, each graded from 0 - 3 with higher scores indicating more severe disease. The sub-scores are stool frequency (0 - 3); rectal bleeding (0 - 3); findings of endoscopy (0 - 3).



Secondary Outcome Measures :
  1. Clinical Response at Week 12 [ Time Frame: Week 12 ]

    A decrease from baseline in the 3-Component Adapted Mayo Score of ≥ 2 points and ≥ 30%, with an accompanying decrease in the sub-score for rectal bleeding of ≥ 1 point or an absolute sub-score for rectal bleeding of ≤ 1.

    The 3-Component Adapted Mayo Score is a measure of UC disease ranging from 0 to 9 points and consists of 3 sub-scores, each graded from 0 - 3 with higher scores indicating more severe disease. The sub-scores are stool frequency (0 - 3); rectal bleeding (0 - 3); findings of endoscopy (0 - 3).


  2. Endoscopic Healing at Week 12 [ Time Frame: Week 12 ]

    Endoscopic Healing (I) defined as an endoscopic sub-score of ≤ 1.

    The endoscopic sub-score is part of the 3-Component Adapted Mayo score and ranges from 0 - 3, with higher scores indicating more severe disease.


  3. Corticosteroid-free clinical response at Week 12 [ Time Frame: Week 12 ]
    Clinical response and achieving a corticosteroid-free status at Week 12 in subjects using oral corticosteroids at the Baseline visit. Clinical response is defined as a decrease from baseline in the 3-Component Adapted Mayo Score of ≥ 2 points and > 30%, with an accompanying decrease in the sub-score for rectal bleeding of ≥ 1 point or an absolute sub-score for rectal bleeding of ≤ 1.

  4. Corticosteroid-free clinical remission at Week 12 [ Time Frame: Week 12 ]
    Clinical remission and achieving a corticosteroid-free status at Week 12 in subjects using oral corticosteroids at the Baseline visit. Clinical remission is defined as a stool frequency sub-score of ≤ 1 associated with a decrease ≥ 1 point from baseline, rectal bleeding sub-score of 0, and an endoscopic sub-score of ≤ 1 using the 3-Component Adapted Mayo Score.

  5. Changes from baseline in individual Adapted Mayo sub-scores at Week 12 [ Time Frame: Week 12 ]
    The Adapted Mayo Score is a measure of UC disease ranging from 0 to 12 points and consists of 4 sub-scores, each graded from 0 - 3 with higher scores indicating more severe disease. The sub-scores are stool frequency (0 - 3); rectal bleeding (0 - 3); findings of endoscopy (0 - 3); and Physician's Global Assessment [PGA] (0 - 3).



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female adult subjects 18 to 75 years old, inclusive.
  2. Willing to provide written informed consent and to be compliant with the schedule of study visits and protocol assessments.
  3. Diagnosis of UC established at least 3 months prior to the Baseline visit, by clinical and endoscopic evidence (colonoscopy or flexible sigmoidoscopy)
  4. Moderately to severely active UC defined as the 3-Component Adapted Mayo Score of 5-9, inclusive, with an endoscopic sub-score of ≥ 2 (from central reading), and a rectal bleeding sub-score of ≥ 1, as determined 10 days (± 3 days) prior to Baseline.
  5. Evidence of active UC, confirmed histologically (from local read), extending proximal to the rectum with ≥ 15 cm of involved colon.
  6. At Screening, a colonoscopy will be required if the subject has had extensive colitis or pancolitis of > 8 years duration or left-sided colitis of > 12 years duration but has not had a colonoscopy within 1 year of the initial screening date. If the subject has had a colonoscopy within 1 year of the initial screening date, a flexible sigmoidoscopy may be used.
  7. Subjects presenting at Screening with moderately to severely active UC demonstrating an inadequate response or loss of response or intolerance/medical contraindication to at least one of the following conventional therapies for UC:

    a. Corticosteroids:

    i. Signs and symptoms of active disease despite treatment with an adequate dose (e.g., prednisolone > 40 mg/day or equivalent) over a period of 4 weeks for oral therapy or intravenously (IV) for up to 1 week or ≥ 9 mg/day oral budesonide;

    OR

    ii. Unable to reduce corticosteroids below the equivalent of prednisolone 10 mg daily orally within 3 months of starting steroids or having experienced a relapse within 3 months of stopping steroids;

    OR

    iii. History of, or current intolerance to corticosteroids (including, but not limited to Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection).

    b. Immunomodulators:

    i. Signs and symptoms of active disease despite at least 3 months of treatment with a sufficient dose (oral azathioprine ≥ 1.5 mg/kg or 6-mercaptopurine [6-MP] ≥ 0.75 mg/kg);

    OR

    ii. History of, or current dose-limiting toxicity associated with use of the agent (e.g., but not limited to nausea/vomiting, abdominal pain, pancreatitis, liver function test [LFT] abnormalities, lymphopenia, TPMT genetic mutation, infection).

    c. Anti-tumor necrosis factor (anti-TNF) agents:

    i. Signs and symptoms of active disease despite treatment with a single anti-TNF agent. Treatment failure is defined as a relapse after an initial response to therapy as follows:

    • Infliximab: At least 4 infusions of at least 5 mg/kg within a 14-week timeframe for induction and maintenance;
    • Adalimumab: Induction regimen incorporating 160 mg at Week 0 (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) and 80 mg at Week 2, followed by maintenance treatment of 40 mg every other week up to at least Week 8;
    • Golimumab: Induction regimen incorporating 200 mg subcutaneous (sc) injection at Week 0, followed by 100 mg at Week 2 and then maintenance treatment of 50 mg or 100 mg (weight dependent) every 4 weeks after completion of the induction regimen up to at least Week 12;

    OR

    ii. History of, or current intolerance (with an initial response), defined as the presence of clinically significant side-effects, including infusion-related hypersensitivity.

    d. Vedolizumab:

    i. Signs and symptoms of active disease despite a history of at least one induction regimen, defined as at least a 14-week (10 weeks in the EU) induction consisting of 300 mg IV at Weeks 0, 2 and 6.

    OR

    ii. History of intolerance to vedolizumab including, but not limited to, serious infections, hepatotoxicity, heart failure, allergic reactions, or any other condition that contributed to discontinuation of the agent.

  8. Subjects receiving oral corticosteroids for the treatment of UC must be on a stable dose of ≤ 40 mg/day (prednisolone or equivalent), or ≤ 9 mg/day budesonide. This dose must be stable from the initial Screening visit until 1 week after the initiation of study treatment.
  9. Subjects receiving oral 5-ASA must be on a stable dose from the initial Screening visit until the end of the study.
  10. Subjects willing to cease the use of any therapeutic enema or suppository or foams, other than that required in preparation for study-mandated colonoscopy/flexible sigmoidoscopies, from the initial Screening visit until the end of the study.
  11. Subjects willing to cease use of azathioprine or 6-MP from the initial Screening visit until the end of the study.
  12. Negative serum pregnancy test in females of childbearing potential at Screening.
  13. If female and of childbearing potential, must agree to be sexually abstinent or use one of the following highly effective methods of birth control from the initial Screening visit until 30 days after the last dose of study drug is administered:

    1. Hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants);
    2. Intrauterine contraceptive system;
    3. Surgical sterilization or partner sterile (must have documented proof);

    AND

    One of the following effective methods of birth control:

    1. Male/female condom;
    2. Cervical cap with spermicide;
    3. Diaphragm with spermicide;
    4. Contraceptive sponge.
  14. Male subjects must be either surgically sterile (must have documented proof), agree to be sexually inactive or use a double-barrier method of birth control (e.g., condom and diaphragm with spermicide, condom with cervical cap and spermicide) from first study drug administration until 90 days after final drug administration.

Exclusion Criteria:

If a subject has any of the following criteria, they will be excluded from the study:

  1. Subjects without previous treatment for UC.
  2. Ulcerative colitis limited to rectum (ulcerative proctitis).
  3. Evidence of acute severe colitis with toxic megacolon, abdominal abscess, bowel stricture or bowel perforation.
  4. A diagnosis of Crohn's colitis, colitis yet to be classified, ischemic colitis, NSAID-induced colitis, idiopathic colitis (i.e., colitis not consistent with UC) or radiation colitis.
  5. Subjects with evidence of pathogenic bowel infection (Clostridium difficile, Escherichia coli, Salmonella, Shigella or Campylobacter).
  6. Previous surgery for UC or, in the opinion of the Investigator, will likely require surgery for UC during the study.
  7. Any histological evidence of mucosal dysplasia.
  8. Subjects with a current or recent history of severe, progressive or uncontrolled cardiac (including uncontrolled hypertension), renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurological (e.g., history of seizures) disease, abnormal magnesium or potassium levels, hypocholesterolemia, or any other severe co-morbidity that, in the opinion of the Investigator, could confound the study results or put the study subject at unreasonable risk.
  9. Malignancies or history of malignancy within 5 years of the initial Screening visit, with the exception of adequately treated or excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin.
  10. Any of the following laboratory abnormalities during the screening period - if values are initially outside the prescribed limits, the evaluation may be repeated once within the screening period to determine eligibility:

    1. Hemoglobin level < 8.0 g/dL
    2. Absolute WBC count < 3.0 × 10^9/L
    3. Absolute Lymphocyte count < 0.5 × 10^9/L
    4. Absolute neutrophil count < 1.2 × 10^9/L
    5. Platelet count < 100 × 10^9/L or >1200 × 10^9/L
    6. ALT or AST > 2.0 × ULN
    7. Alkaline phosphatase > 2.0 × ULN
    8. Serum creatinine > 1.5 × ULN
    9. Bilirubin > 1.5 × ULN
  11. Subjects with active TB infection or known history of prior treated or untreated TB infection.
  12. Subject with a positive serology test result for HIV (HIV type 1 or type 2).
  13. Subject with a positive serology test result for active HBV or HCV infection.
  14. Treatment with biologic agents for UC within 56 days or 5 half-lives (whichever is greater) prior to the Baseline visit.
  15. Treatment with any calcineurin inhibitor (e.g. cyclosporine or tacrolimus) within 28 days prior to the Baseline visit.
  16. Treatment with methotrexate or JAK inhibitors (e.g. tofacitinib) from the initial Screening visit until the end of the study.
  17. Initiation of treatment with an oral or IV corticosteroid from the initial Screening visit until the end of the study.
  18. Use of any strong inhibitors of CYP enzymes (e.g., cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, grapefruit juice and HIV antivirals) within 14 days prior to the Baseline visit.
  19. Use of strong or moderate P-gp inhibitors (e.g., amiodarone, azithromycin, clarithromycin, itraconazole, ketoconazole, dronedarone, lapatinib, quinidine, ranolazine, verapamil) within 14 days prior to the Baseline visit.
  20. Use of any herbal medication for the treatment of UC or which might interfere with CYP enzymes within 14 days prior to the Baseline visit.
  21. Subjects vaccinated with a live or live-attenuated vaccine within 14 days of the Baseline visit, or planned vaccination during conduct of the study.
  22. Subjects with a QTcF of > 450 ms for males and > 470 ms for females at Screening.
  23. A history of risk factors for Torsades de pointes (e.g., history of heart failure, hypokalemia, family history of Long QT Syndrome).
  24. Known hypersensitivity to cyclosporine or any excipients contained in ST-0529.
  25. History of alcohol or drug abuse in the year prior to the initial Screening visit.
  26. Subjects currently breast feeding, pregnant, or unwilling to delay initiation of breast feeding for at least 90 days after the last dose of study drug is administered.
  27. Participation in another clinical trial and having received investigational medication within 30 days or within 5 half-lives (whichever is longer) prior to the Baseline visit, or concurrent participation in another clinical trial.
  28. Subjects who, in the opinion of the Investigator, are unsuitable for inclusion in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03844932


Contacts
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Contact: Sublimity Therapeutics (HoldCo) Ltd +1 619-333-8911 info@sublimitytherapeutics.com

Locations
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United States, California
Sharp Chula Vista eStudy Site Recruiting
Chula Vista, California, United States, 91911
Contact: Michael Waters, MD    619-955-5246      
Palmtree Clinical Research Inc Recruiting
Palm Springs, California, United States, 92262
Contact: Homan Abdollahzadeh, MD    760-778-7799      
United States, Florida
Advanced Research Institute Recruiting
Largo, Florida, United States, 33377
Contact: Jatin Bidani, MD    713-559-7351      
Meridien Research Recruiting
Spring Hill, Florida, United States, 34609
Contact: Gigi Claire Lefebvre, MD    352-597-8839      
United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: Atsushi Sakuraba, MD    773-834-7414      
United States, Indiana
IU Research, an Affiliate of Aerotek, Division of Gastroenterology/Hepatology Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Sashidhar Sagi, MD    713-559-7351      
United States, Maryland
Capitol Research Recruiting
Rockville, Maryland, United States, 20850
Contact: Ajay Bakhshi, MD    301-417-8080      
United States, Texas
Spring Gastroenterology Associates Recruiting
Houston, Texas, United States, 77002
Contact: Ravi Moparty, MD    281-888-5564      
Biopharma Informatic, LLC Recruiting
Houston, Texas, United States, 77043
Contact: Mouhamad Al-Sabbagh, MD    281-768-5879      
Biopharma Informatic, LLC. Recruiting
Houston, Texas, United States, 77084
Contact: James Maher, III, MD    281-944-3610    info@clinicalrc.net   
Rio Grande Gastroenterology Recruiting
McAllen, Texas, United States, 78503
Contact: Ralph Alhalel, MD    281-944-3610    info@clinicalrc.net   
Poland
Medicome Sp. z o.o. Recruiting
Oświęcim, Poland, 32600
Contact: Witold Zmuda, MD    +48 22-616-14-88      
Spain
Hospital Universitario Virgen de la Macarena Recruiting
Sevilla, Spain, 41009
Contact: Federico Arguelles Arias, MD    +34 600162109      
Sponsors and Collaborators
Sublimity Therapeutics Holdco Limited
Dr. Falk Pharma GmbH
Investigators
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Study Director: Sponsor Responsible Medical Officer Sublimity Therapeutics (HoldCo) Ltd

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Responsible Party: Sublimity Therapeutics Holdco Limited
ClinicalTrials.gov Identifier: NCT03844932     History of Changes
Other Study ID Numbers: CYC-202
First Posted: February 19, 2019    Key Record Dates
Last Update Posted: June 10, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors