Evaluation of MORF-057 Efficacy, Safety, and Tolerability in Adults with Moderately to Severely Active Ulcerative Colitis: A Phase 2a Open-label Study

Trial ID: 2024-516960-27-00
Protocol: MORF-057-201
Sponsor: Morphic Therapeutic Inc.

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Diseases & Conditions

Colitis ulcerative

Objectives

The primary objective of this Phase 2a, open-label, single-arm study is to evaluate the effects of **MORF-057** on histologic improvement at Week 12 in adults with moderately to severely active **ulcerative colitis**. This objective is clinically relevant as histologic improvement is a critical marker of disease activity and treatment efficacy in ulcerative colitis, potentially leading to better patient outcomes.

Secondary objectives include:

To assess the safety and tolerability of MORF-057, which is essential for determining the risk-benefit profile of the treatment.
To evaluate the effect of MORF-057 on clinical improvement at Week 12, providing insights into the potential symptomatic benefits for patients.
To characterize the pharmacokinetics (PK) of MORF-057, which will help in understanding the drug's absorption, distribution, metabolism, and excretion, crucial for optimizing dosing regimens.

Participants

The clinical trial involves a total of **8 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population includes both male and female subjects, aged between **18 to 85 years**, who are capable of providing informed consent. Participants were selected based on their medical history and current health status, ensuring they have had symptoms of ulcerative colitis for at least three months prior to screening. The trial includes individuals who are either treatment-naïve or have had an inadequate response, loss of response, or intolerance to a limited number of specific medications. Participants are required to adhere to certain lifestyle considerations, such as maintaining stable doses of permitted medications and following contraception guidelines. The study also considers individuals who have previously been treated with vedolizumab, provided they meet specific washout criteria. The trial population is not restricted by gender, and it includes a vulnerable population, ensuring a comprehensive evaluation of the investigational product's effects.

Plans and Procedures

The clinical trial is designed as a **Phase 2a**, open-label, single-arm study to evaluate the efficacy, safety, and tolerability of **MORF-057** in adults with moderately to severely active **ulcerative colitis**. The primary objective is to assess the effects of MORF-057 on histologic improvement at Week 12. The trial will involve participants aged 18 to 85 years who meet specific inclusion criteria, including a confirmed diagnosis of moderately to severely active ulcerative colitis for at least three months prior to screening. The study will measure the change from baseline to Week 12 in the Robarts Histopathology Index (RHI) Score as the primary endpoint, with secondary endpoints including frequencies and proportions of treatment-emergent adverse events (TEAEs), changes in the Modified Mayo Clinic Score (MCS), and MORF-057 concentration in plasma.

Participants will be involved in the study for a maximum treatment period of 78 weeks, with the trial estimated to conclude by February 18, 2025. The study will commence with a screening visit to confirm eligibility based on the inclusion criteria, such as a Modified Mayo Clinic Score of 5 to 9 and evidence of ulcerative colitis extending at least 15 cm from the anal verge. Following the screening, participants will undergo regular follow-up visits to monitor safety, efficacy, and pharmacokinetics, with the final visit marking the end of the study. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or the occurrence of significant adverse events. The study drug, MORF-057, will be administered orally in capsule form, with a maximum daily dose of 200 mg. Participants are required to adhere to specific washout periods for prior ulcerative colitis therapies and maintain stable doses of concomitant medications, except for tapering oral corticosteroids after 12 weeks in the trial.

Treatment

The clinical trial involves the administration of **MORF-057**, an investigational medication developed by Morphic Therapeutic, Inc. **MORF-057** is formulated as a **capsule** and is intended for **oral use**. The active substance in the capsule is chemically derived and is identified as **MORF-057**. The maximum daily dose of **MORF-057** is 200 mg, with a total maximum dose of 109.2 grams over the course of the study. The treatment period extends up to 78 weeks. The primary objective of the trial is to evaluate the efficacy, safety, and tolerability of **MORF-057** in adults with moderately to severely active **ulcerative colitis**. The study is designed as a Phase 2a, open-label, single-arm trial, focusing on histologic improvement at Week 12.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is structured to monitor participant compliance with the dosing schedule, ensuring adherence to the prescribed regimen. The pharmaceutical form of the investigational product is a capsule, which facilitates ease of administration and compliance monitoring. The trial does not include any pediatric formulations, and the investigational product is not classified as an orphan drug. The study protocol ensures that all participants receive the investigational product under controlled conditions to assess its therapeutic potential in the target population.

Efficacy

The efficacy of MORF-057 in the treatment of moderately to severely active **Ulcerative Colitis** will be assessed through a Phase 2a, open-label, single-arm clinical trial. The primary endpoint for evaluating efficacy is the change from baseline to Week 12 in the Robarts Histopathology Index (RHI) Score. This index is a validated tool used to measure histologic improvement in patients with Ulcerative Colitis. Secondary endpoints include the change from baseline to Week 12 in the Modified Mayo Clinic Score (MCS), which assesses clinical symptoms, and the measurement of MORF-057 concentration in plasma, along with plasma pharmacokinetic (PK) parameters.

Efficacy parameters will be collected and analyzed at specific timepoints, with the primary assessment occurring at Week 12. The trial will utilize laboratory tests and validated scales to ensure accurate and reliable data collection. The study is designed to provide comprehensive insights into the efficacy of MORF-057, with a focus on both histologic and clinical outcomes in the target patient population.

Inclusion and Exclusion Criteria

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Inclusion Criteria

18 to 85 years of age, inclusive, at the time of signing the Informed Consent Form (ICF).
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).
Has an RHI Score of 10 or greater.
Has evidence of UC extending at least 15 cm from the anal verge.
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-α 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).
Meets the following wash out criteria of prior UC therapy relative to study Day 1: a. TNF-α 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.
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 study Day 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.
In the opinion of the Investigator, the patient can fully participate in all aspects of this clinical study.
Has a body mass index (BMI) within the range of 18.0 and 40.0 kg/m2 (inclusive) at Screening.
A participant is eligible to participate if he/she agrees to obide by the guidelines set forth in this protocol regarding contraception requirements.
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).
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Exploratory Cohort: Those intolerant to (e.g. infusion-related skin reaction, allergy, or side effects unrelated to α4β7 inhibition) or secondary non-responders to vedolizumab who have been dosed within the past 5 years with the drug.
Exploratory Cohort: The participants should also have received their last dose of vedolizumab at least 6 weeks prior to study Day 1 to allow sufficient washout.

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Exclusion Criteria

Diagnosed with indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, or CD or has clinical findings suggestive of CD.
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.
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.
Has had a surgical procedure requiring general anesthesia within 30 days prior to Screening.
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.
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.
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.
Has a positive diagnostic tuberculosis (TB) test at Screening.
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.
Had any vaccination (including live virus vaccinations) within 3 weeks prior to study Day 1.
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 disorder) that, in the judgement of the Investigator, would compromise compliance with the protocol, interfere with interpretation of the study results, or predispose participants to safety risks.
Has a known primary or secondary immunodeficiency.