A Phase 2a study to evaluate the Efficacy, Safety, and Tolerability of MORF-057 in Ulcerative Colitis

Phase 1

• Conditions: Moderate to Severe Ulcerative Colitis; MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2021-005288-31-PL
• Lead Sponsor: Morphic Therapeutic, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-05-19
• Last Update Posted: 19 December 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. 18 to 85 years of age, inclusive, at the time of signing the Informed Consent Form (ICF).
2. Participant has had signs/symptoms of moderately to severely active UC for at least 3 months prior to
Screening, and the diagnosis was confirmed during the Screening Period with the
following criteria: a Modified MCS of 5 to 9 (inclusive) with an MES =2 (confirmed by
central reader).
3. Has an RHI Score of 10 or greater
4. Has evidence of UC extending at least 15 cm from the anal verge
5. Is an AT-naïve participant or a participant who had an inadequate response, loss of response, or intolerance to no more than 3 drugs in 2 classes of the following:
a. TNF-a antagonists, including infliximab, adalimumab, or golimumab
b. Interleukin (IL)-12/IL-23 antagonists, including ustekinumab
c. JAK antagonists, including tofacitinib and upadacitinib
d. S1P receptor agonists, including ozanimod
e. Any investigational product with the same mechanism as one of those outlined
above (5a through 5d)
f. Integrin inhibitors, including vedolizumab (participants in the Exploratory Cohort
only)
6. Meets the following wash out criteria of prior UC therapy relative to study Day 1:
a. TNF-a antagonists: at least 8 weeks
b. IL-12/IL-23 antagonists, including ustekinumab: at least 8 weeks
c. JAK antagonists, including tofacitinib and upadacitinib: at least 2 weeks
d. S1P receptor agonists, including ozanimod: at least 4 weeks
7. If the participant has been receiving any of the non-prohibited medications for UC listed below, he/she must discontinue use at least 5 half-lives before study Day 1 or must agree to maintain stable doses of these concomitant medications starting from the time specified below until the end of the Safety Follow-up Period, with the exception of tapering oral corticosteroid dose after 12 weeks of being in the trial.
a. 5-Aminosalicylates (not exceeding 4.8 g per day): at least 2 weeks prior to studyDay 1
b. Oral corticosteroids (not exceeding prednisone 30 mg per day, budesonide 9 mg per day, or equivalent): at least 2 weeks prior to study Day 1
c. 6-Mercaptopurine (any stable dose): at least 4 weeks prior to study Day 1
d. Azathioprine (any stable dose): at least 4 weeks prior to study Day 1
e. Methotrexate (any stable dose): for at least 4 weeks prior to study Day 1
8. In the opinion of the Investigator, the patient can fully participate in all aspects of this
clinical study
9. Has a body mass index (BMI) within the range of 18.0 and 40.0 kg/m2 (inclusive) at Screening
10. A participant is eligible to participate if he/she agrees to abide by the guidelines set forth in this protocol regarding contraception requirements
11. For the study Treatment Period and at least 28 days after receiving the last dose of MORF-057, male participants must agree not to donate sperm and female participants must agree not to donate eggs (ova, oocytes).
12. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol

Exploratory Cohort Inclusion Criteria:
In addition to meeting Inclusion Criteria 1 through 12, the following criteria must be met for participants to be included in the Exploratory Cohort:
13. Those intolerant to (e.g. infusion-related skin reaction, allergy, or side effects unrelated to a4ß7 inhibition) or secondary non-responders to vedolizumab who have been dosed within the past 5 years with the drug. Up to 5 of the 10 Exploratory Cohort participants may be includ

Exclusion Criteria

1. Diagnosed with indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, or CD or has clinical findings suggestive of CD.
2. Has current evidence of un-resected colonic dysplasia or un-resected adenomatous colonic polyps or evidence of toxic megacolon, abdominal abscess, symptomatic colonic stricture, fistula, stoma, ileostomy, or colostomy at Screening.
3. Currently requires or is anticipated to require surgical intervention for UC during the study or is planning to undergo major surgery during the study period.
4. Has had a surgical procedure requiring general anesthesia within 30 days prior to Screening.
5. Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating, or neurodegenerative disease. For questions about whether this applies to a specific case, consult with the Medical Monitor.
6. Has positive findings on a subjective neurological screening questionnaire or progressive multifocal leukoencephalopathy (PML) subjective symptom checklist during Screening or prior to the administration of the first dose of study drug on study Day 1
7. Has an active bacterial, viral or parasitic pathogenic enteric infection, including Clostridium difficile; has cytomegalovirus, hepatitis B or C virus, or human immunodeficiency virus (HIV); had an infection requiring hospitalization or intravenous antimicrobial therapy,
or an opportunistic infection within 3 months prior to Screening; had any infection requiring oral antimicrobial therapy within 2 weeks prior to Screening; or has a history of more than 1 episode of herpes zoster or any episode of disseminated herpes zoster infection
8. Has a positive diagnostic tuberculosis (TB) test at Screening (defined as a positive QuantiFERON test). If the participant has had a confirmed negative QuantiFERON or other Interferon Gamma Release Assay test within 90 days prior to Screening, the test does not need to be repeated. In cases where the QuantiFERON test result is indeterminate, the participant may have the test repeated once, and if the second test is negative, the participant will be eligible. In the event the second test also has an indeterminate result or QuantiFERON is unavailable, the Investigator has the option to perform a purified protein derivative (PPD) skin test. If the PPD reaction is <5 mm, then the participant is eligible. If the reaction is =5 mm or PPD testing is not done, the participant is not eligible. An exception can be made for participants with a history of latent TB who are currently receiving treatment for latent TB per local standard care, who will initiate treatment for latent TB before the first dose of study drug, or who have documentation of completing appropriate treatment for latent TB within 2 years prior to study Day 1.
9. Tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Screening Period. Participants who test positive for SARS-CoV-2 can undergo retesting throughout the Screening Period. Testing to be performed according to site-specific testing procedures and country-specific requirements.
10. Had any vaccination (including live virus vaccinations) within 3 weeks prior to study Day 1.
11. Has a concurrent, clinically significant, serious, unstable comorbidity (such as uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disord

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effects of MORF-057 on histologic improvement at Week 12;Secondary Objective: To assess the safety and tolerability of MORF-057<br>To evaluate the effect of MORF-057 on clinical improvement at Week 12<br>To characterize the PK of MORF-057;Primary end point(s): Change from baseline to Week 12 in the Robarts Histopathology Index (RHI) Score;Timepoint(s) of evaluation of this end point: Week 0, Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Frequencies and proportions for treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and TEAEs leading to study drug discontinuation<br>- Change from baseline to Week 12 in the Modified Mayo Clinic Score (MCS)<br>- MORF-057 concentration in plasma<br>- Plasma PK parameters<br>;Timepoint(s) of evaluation of this end point: - Frequencies and proportions for treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and TEAEs leading to study drug discontinuation <br> between administration of the first dose of study drug and 7 days after the last dose of study drug<br><br>- Change from baseline to Week 12 in the Modified Mayo Clinic Score (MCS) <br> Week 0, Week 12<br><br>- MORF-057 concentration in plasma <br> Week 0 - Week 52<br><br>- Plasma PK parameters <br> Week 0 - Week 52<br>