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

NCT03844932 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: CYC-202
• Study Type: interventional
• Target: 235
• Locations: 17 countries
• Sites: 89

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).

Conditions

Colitis, Ulcerative

Outcome Measures

Primary Outcomes (1)

• Clinical Remission at 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).

  Week 12

Secondary Outcomes (5)

• Clinical Response at Week 12

  Week 12

• Endoscopic Healing at Week 12

  Week 12

• Corticosteroid-free clinical response at Week 12

  Week 12

• Corticosteroid-free clinical remission at Week 12

  Week 12

• Changes from baseline in individual Adapted Mayo sub-scores at Week 12

  Week 12

Study Arms (4)

ST-0529 18.75 mg*

EXPERIMENTAL

ST-0529: 18.75 mg orally twice daily (BID) \*Jan 2021 update: following the IDMC recommendation, this arm has been dropped

Drug: ST-0529

ST-0529 37.5 mg*

EXPERIMENTAL

ST-0529: 37.5 mg orally twice daily (BID) \*Jan 2021 update: following the IDMC recommendation, this arm has been dropped

Drug: ST-0529

ST-0529 75 mg

EXPERIMENTAL

ST-0529: 75 mg orally twice daily (BID)

Drug: ST-0529

Matching Placebo

PLACEBO COMPARATOR

Placebo: matching placebo orally twice daily (BID)

Drug: ST-0529

Interventions

ST-0529 DRUG

ST-0529 utilizes SmPill® technology to encapsulate the otherwise insoluble cyclosporine in a presolubilized, lipid-based formulation.

Also known as: cyclosporine

Matching Placebo; ST-0529 18.75 mg*; ST-0529 37.5 mg*; ST-0529 75 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adult subjects 18 to 75 years old, inclusive.
• Willing to provide written informed consent and to be compliant with the schedule of study visits and protocol assessments.
• Diagnosis of UC established at least 3 months prior to the Baseline visit, by clinical and endoscopic evidence (colonoscopy or flexible sigmoidoscopy)
• 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.
• Evidence of active UC, confirmed histologically (from local read), extending proximal to the rectum with ≥ 15 cm of involved colon.
• 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.
• 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;
• 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;
• 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);
• 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:

You may not qualify if:

• If a subject has any of the following criteria, they will be excluded from the study:
• Subjects without previous treatment for UC.
• Ulcerative colitis limited to rectum (ulcerative proctitis).
• Evidence of acute severe colitis with toxic megacolon, abdominal abscess, bowel stricture or bowel perforation.
• 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.
• Subjects with evidence of pathogenic bowel infection (Clostridium difficile, Escherichia coli, Salmonella, Shigella or Campylobacter).
• Previous surgery for UC or, in the opinion of the Investigator, will likely require surgery for UC during the study.
• Any histological evidence of mucosal dysplasia.
• 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.
• 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.
• 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:
• Hemoglobin level \< 8.0 g/dL
• Absolute WBC count \< 3.0 × 10\^9/L
• Absolute Lymphocyte count \< 0.5 × 10\^9/L
• Absolute neutrophil count \< 1.2 × 10\^9/L

Sponsors & Collaborators

• Sublimity Therapeutics Holdco Limited: lead
• Dr. Falk Pharma GmbH: collaborator

Study Sites (89)

Palmtree Clinical Research Inc

Palm Springs, California, 92262, United States

Location

Advanced Research Institute

Largo, Florida, 33377, United States

Location

Advanced Research Institute, Inc.

New Port Richey, Florida, 34653, United States

Location

Endoscopic Research Inc

Orlando, Florida, 32803, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

AGA Clinical Reasearch Associates, LLC

Egg Harbor, New Jersey, 08234, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Biopharma Informatic, LLC.

Houston, Texas, 77084, United States

Location

Grodno Regional Clinical Hospital

Grodno, 230017, Belarus

Location

Gomel Regional Clinical Hospital

Homyel, 246 029, Belarus

Location

City Clinical Emergency Hospital

Minsk, 220024, Belarus

Location

MedConsult Pleven

Pleven, 5800, Bulgaria

Location

Medical Center Asklepion

Sofia, 1303, Bulgaria

Location

UMBAL Tsaritsa Joanna ISUL

Sofia, 1527, Bulgaria

Location

Dalhousie University - Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

CHU Amiens Picardie - Service Hépato-Gastroentérologie

Amiens, 80054, France

Location

CHU DE MONTPELLIER - Hôpital St ELOI

Montpellier, 34295, France

Location

CHU de Saint-Etienne - Service de Gastro-Entérologie-Hépatologie

Saint-Etienne, 42055, France

Location

Hôpital de Brabois Service d'Hépato-Gastro-Entérologie

Vandœuvre-lès-Nancy, 54511, France

Location

Eugastro GmbH

Leipzig, Saxony, 4103, Germany

Location

Medizinische Klinik für Gastroenterologie, Infektiologie, Rheumatologie charite

Berlin, 12203, Germany

Location

Krankenhaus Walfriede, Akademisches Lehrkrankenhaus der Charite

Berlin, 14163, Germany

Location

Klinik für Gastroenterologie, Pulmologie und allg. lnnere Medizin

Cologne, 5103, Germany

Location

Agaplesion Markus Krankenhaus Medizinischen Klinik I, Gastroenterologie, Hepatologie, Onkologie, lnfektiologie

Frankfurt, 60431, Germany

Location

Universitatsklinikum Freiburg, Medizinische Klinik

Freiburg im Breisgau, 79106, Germany

Location

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Zentrym für Innere Medizin

Hanover, 30625, Germany

Location

Universität Leipzig, Klinik f. Gastroenterologie und Rheumatologie

Leipzig, 4103, Germany

Location

Gastroenterologische Gemeinschaftspraxis Minden

Minden, 32123, Germany

Location

DRC Gyógyszervizsgáló Központ Kft.

Balatonfüred, 8230, Hungary

Location

Semmelweis University

Budapest, 1088, Hungary

Location

Semmelweis University, AOK Varosmajori Sziv- es Ergyogyaszati Klinika,

Budapest, H-1031, Hungary

Location

Bugat Pal Hospital

Gyöngyös, 3200, Hungary

Location

Mater Misericordiae University Hospital

Dublin, D07 RX49, Ireland

Location

St. James's Hospital

Dublin, Ireland

Location

Gastroenterology Institute, Emek Medical Center

Afula, 1834111, Israel

Location

Barzilai Medical Center

Ashkelon, 7830604, Israel

Location

Clalit Health Services Jerusalem

Jerusalem, 9362410, Israel

Location

Institute of Gastroenterology, Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Humanitas Research Hospital, IBD Center

Milan, 20089, Italy

Location

A.0.U. di Modena - Policlinico S.C. di Gastroenterologia

Modena, 41124, Italy

Location

Fondazione IRCCS Policlinico San Matteo - Medicina Generale I

Pavia, 27100, Italy

Location

ASST Rhodense - Ospedale di Rho

Rho, 20017, Italy

Location

Fondazione Casa Sollievo della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

Centrum Opieki Zdrowotnej Orkan-med

Ksawerów, 95-054, Poland

Location

Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego UM

Lodz, 90-153, Poland

Location

Medicome Sp. z o.o.

Oświęcim, 32600, Poland

Location

Centrum Medyczne Medyk

Rzeszów, 35-526, Poland

Location

Endoskopia sp. z o.o.

Sopot, 81-756, Poland

Location

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, 00-728, Poland

Location

MedLife Grivita

Bucharest, 010719, Romania

Location

Colentina Clinical Hospital

Bucharest, 020125, Romania

Location

University Hospital Bucharest

Bucharest, 050098, Romania

Location

Federal State Center of Coloproctology

Moscow, 123423, Russia

Location

LLC Medical center Healthy family

Novosibirsk, 630099, Russia

Location

Military Medical Academy

Saint Petersburg, 191 124, Russia

Location

North-Western State Medical University n.a. I.I.Mechnikov

Saint Petersburg, 191015, Russia

Location

Saint-Petersburg State Medical Academy n.a. I.I. Mechnikov of Federal Agency of Healthcare & Social Development

Saint Petersburg, 195067, Russia

Location

Scientific Research Center Eco-Safety LLC

Saint Petersburg, 196143, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

Non state Public Health Institution "Railway clinical hospital on station Samara" of joint stock company Russian railways

Samara, 403029, Russia

Location

Saratov State Medical University

Saratov, 410054, Russia

Location

Siberia State Medical University

Tomsk, 630055, Russia

Location

Clinical Center Zvezdara

Belgrade, 11000, Serbia

Location

Clinical Hospital Center "Dr Dragisa Misovic-Dedinje"

Belgrade, 11000, Serbia

Location

Clinical-Hospital Centre Bezanijska Kosa - Gastroenterology Department

Belgrade, 11080, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Hospital Universitario Virgen de la Macarena

Seville, 41009, Spain

Location

Chernivtsi Regional Clinical Hospital

Chernivtsi, 58001, Ukraine

Location

Ivano-Frankivsk National Medical University, Regional Clinical Hospital

Ivano-Frankivsk, 76008, Ukraine

Location

Kharkiv City Clinical Hospital No 2 n.a. prof. O.O.Shalimov

Kharkiv, 61037, Ukraine

Location

Kiev City Clinical Hospital No. 1

Kiev, 2091, Ukraine

Location

Communal Institution of Kyiv Regional Council "Kyiv Regional Clinical Hospital"

Kyiv, 04107, Ukraine

Location

Ukrainian-German Gastroenterology Center "BYK-Kyiv"

Kyiv, 1030, Ukraine

Location

Volyn Regional Clinical Hospital

Lutsk, 43000, Ukraine

Location

Communal Nonprofit Enterprise "Lviv Clinical Emergency Care Hospital"

Lviv, 79059, Ukraine

Location

Communal Nonprofit Entreprise, "Lviv Clinical Emergency Care Hospital", 1st Therapeutic Dpt

Lviv, 79059, Ukraine

Location

Communal Nonprofit Enterprise "Odesa Regional Clinical Hospital"

Odesa, 65025, Ukraine

Location

Communal Nonprofit Enterprise "Ternopil University Hospital" of Ternopil Regional Council

Ternopil, 46002, Ukraine

Location

Municipal Institution "Uzhhorod Central District Hospital"

Uzhhorod, 88009, Ukraine

Location

Medical Center "Health Clinic"

Vinnytsia, 21000, Ukraine

Location

Communal Non-profit Enterprise "Vinnytsia City Clinical Hospital #1"

Vinnytsia, 21029, Ukraine

Location

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

South Eastern Health & Social Care Trust, Ulster Hospital

Belfast, Co Antrim, BT161RH, United Kingdom

Location

Royal Liverpool & Broadgreen University Hospitals NHS Trust

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust

Birmingham, Warwickshire, B15 2TH, United Kingdom

Location

Barnsley Hospital NHS Foundation Trust

Barnsley, Yorkshire, S75 2EP, United Kingdom

Location

University College London Hospital NHS Foundation Trust

London, NWI 2BU, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE59RS, United Kingdom

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Sponsor Responsible Medical Officer

  Sublimity Therapeutics (HoldCo) Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will investigate ST-0529 doses of 18.75 mg BID, 37.5 mg BID, or 75 mg BID, versus matching placebo BID.

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 19, 2019
• Study Start: January 24, 2019
• Primary Completion: April 14, 2021
• Study Completion: April 14, 2021
• Last Updated: May 7, 2021

Record last verified: 2021-05

Locations

IT (5); RO (3); BU (3); PL (6); BE (3); RU (10); SE (4); DE (9); HU (4); IE (2); UA (14); GB (7); IL (4); ES (1); CA (2); US (8); FR (4)