A Phase 2 Study to Evaluate MORF-057 in Adults with Moderately to Severely Active Crohn’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Morphic Therapeutic Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

25 Jun 2024 → ongoing

Decision date (initial)

2024-05-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Morphic Therapeutic, Inc.

External identifiers

EU CT number

2023-508158-24-00

WHO UTN

U1111-1297-7265

ClinicalTrials.gov

NCT06226883

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Therapy, Efficacy, Safety

Primary Efficacy: To evaluate the effect of MORF-057 on endoscopic response at Week 14

Secondary objectives 2

1. Secondary Efficacy: - To evaluate the effect of MORF-057 on clinical response as determined using the Crohn’s Disease Activity Index (CDAI) at Week 14; -To evaluate the effect of MORF-057 on CDAI clinical remission at Week 14.
2. Safety: To assess the safety and tolerability of MORF-057.

Conditions and MedDRA coding

Moderately to Severely Active Crohn’s Disease

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Male or female, 18 to 85 years of age, inclusive, at the time of signing the Informed Consent Form (ICF).
2. 9. Has a body mass index (BMI) ≥18.0 at Screening.
3. 11. For the study Treatment Period and at least 90 days after receiving the last dose of MORF-057, male participants must agree not to donate sperm. For the study Treatment Period and at least 28 days after receiving the last dose of MORF-057, female participants must agree not to donate eggs (ova, oocytes).
4. 12. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
5. 2. Participant has had a diagnosis of CD supported by signs/symptoms, endoscopy, and histology for at least 90 days prior to Screening. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the Investigator, must be available.
6. 3. Moderately to severely active CD was confirmed during the Screening Period with the following criteria: a) A CDAI score of 220 to 450 inclusive b) An SES-CD score of ≥6. If disease is isolated to the ileum, the requirement will be an SES-CD score ≥4. c) Additional inflammatory markers hs-CRP>5 mg/L and/or fecal calprotectin >250 µg/g.
7. 4. Average daily stool score ≥4 points and/or an average daily abdominal pain score of ≥2 points.
8. 5. Demonstrated an inadequate response, loss of response, or intolerance to at least one of the following treatments (including corticosteroids, immunosuppressants, and/or advanced therapies for CD) in the opinion of the Investigator: a. Corticosteroids b. Immunosuppressants (e.g., azathioprine, 6-mercaptopurine, or methotrexate) c. Advanced therapies for CD (e.g., biologic agents, JAK inhibitors, or applicable investigational products [including blinded study treatments in placebo-controlled trials, however, if participants can document that they received only placebo, they will be considered advanced therapy naïve]).
9. 6. Meets the following washout criteria of prior CD therapy relative to study Day 1: a. TNF-α antagonists: at least 5 half-lives; b. IL-12/IL-23 antagonists, including ustekinumab: at least 5 half-lives; c. IL-23 antagonists, including risankizumab, guselkumab or mirikizumab: as least 5 half-lives; d. JAK inhibitors, including tofacitinib or upadacitinib: at least 1 week.
10. 7. If the participant has been receiving any of the non-prohibited medications for CD 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 SFU Period, with the exception of tapering oral corticosteroid dose after completion of the Induction Period. a. Oral 5-aminosalicylates (not exceeding 4.8 g per day): at least 2 weeks prior to Screening ileocolonoscopy; b. Oral corticosteroids (not exceeding prednisone 20 mg/day, budesonide 9 mg/day, beclomethasone dipropionate 5 mg/day, methylprednisolone 24 mg/day, or equivalent): at least 2 weeks prior to Screening ileocolonoscopy; c. 6-Mercaptopurine (any stable dose): at least 4 weeks prior to Screening ileocolonoscopy; d. Azathioprine (any stable dose): at least 4 weeks prior to Screening ileocolonoscopy; e. Methotrexate (any stable dose): at least 4 weeks prior to Screening ileocolonoscopy.
11. 8. In the opinion of the Investigator, the participant can fully participate in all aspects of this clinical study.
12. 10. A participant is eligible to participate if he/she agrees to abide by the guidelines regarding contraception requirements: a. A male participant is eligible to participate if he agrees to the following during the study Treatment Period and for at least 90 days after receiving the last dose of MORF-057: • Agrees to abstain from heterosexual intercourse as his preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR • Agrees to use a male condom, with female partner use of an additional contraceptive method; b. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a woman of non-childbearing potential OR • Is a woman of childbearing potential and agrees to use a contraceptive method that is highly effective with a failure rate of <1% per year together with a barrier method used by her or her male partner during the study Treatment Period and for at least 28 days after receiving the last dose of MORF-057.

Exclusion criteria 37

1. 1. Diagnosed with indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, or UC, or has clinical findings suggestive of UC.
2. 7. Currently requires or is anticipated to require surgical intervention for CD during the study duration.
3. 8. Has had a surgical procedure requiring general anesthesia within 30 days prior to Screening or is planning to undergo major surgery during the study period.
4. 9. Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating, or neurodegenerative disease.
5. 13. Had any vaccination (including live virus vaccinations) within 3 weeks prior to study Day 1.
6. 14. 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, in consultation with the Sponsor Medical Monitor, would compromise compliance with the protocol, interfere with interpretation of the study results, or pre-dispose participants to safety risks.
7. 15. Has a known primary or secondary immunodeficiency.
8. 16. Has a history of myocardial infarction, unstable angina, transient ischemic attack, decompensated heart failure requiring hospitalization, congestive heart failure (New York Heart Association Class 3 or 4), uncontrolled arrhythmias, cardiac revascularization, uncontrolled hypertension, or uncontrolled diabetes within 6 months of Screening.
9. 17. Has a known history of left ventricular ejection fraction (LVEF) <50%.
10. 18. Has a clinically significant abnormal ECG at Screening, including a QT interval corrected through use of Fridericia’s formula (QTcF) ≥450 ms for males and ≥470 ms for females.
11. 19. Abnormal hematology (hemoglobin level, white blood cell [WBC] count, or platelet count) or coagulation results at Screening, as evidenced by the ranges provided below: a. Hemoglobin level <8.0 g/dL; b. Absolute WBC count <3.0x10^9/L; c. Absolute lymphocyte count <0.5x10^9/L or >5.5x10^9/L; d. Absolute neutrophil count <1.2x10^9/L; e. Platelet count <100x10^9/L or 1000x10^9/L; f. International normalized ratio >1.5.
12. 10. Has positive findings on a Subjective Progressive Multifocal Leukoencephalopathy (PML) Checklist during Screening or prior to the administration of the first dose of study drug on study Day 1.
13. 20. Clinically significant abnormal urinalysis results, as deemed by the Investigator or designee.
14. 21. Abnormal organ function at Screening, as evidenced by the following: a. Alanine transaminase (ALT) or aspartate transaminase (AST) >2.0 × upper limit of normal (ULN) b. Chronic kidney disease stages 4 and 5, defined as having a glomerular filtration rate <30 mL/min/1.73 m^2 as calculated using the Modification of Diet in Renal Disease (MDRD) equation (National Kidney Foundation), receiving dialysis, or being listed for or has received a renal transplant c. Total bilirubin ≥1.5×ULN unless the patient has documented diagnosis of Gilbert’s syndrome and other diseases that can present with hyperbilirubinemia have been ruled out.
15. 22. History of active malignancy in the 5 years preceding study Day 1, except in cases of basal cell skin cancer, squamous cell skin cancer, or other in-situ malignancies that have been excised and resolved and the participant was deemed clear of cancer after appropriate follow-up. Participants with a history of malignancy or those at high risk for malignancy may only be enrolled after a consultation with the Medical Monitor.
16. 11. Has a potentially active bacterial, viral, or parasitic pathogenic enteric infection, including Clostridioides difficile (C. difficile); has hepatitis B or C virus, or human immunodeficiency virus (HIV); had an infection requiring hospitalization or intravenous antimicrobial therapy, or an opportunistic infection within 90 days 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.
17. 12. Has active tuberculosis (TB), as evidenced by any of the following: a. A diagnostic test for TB performed within 30 days prior to Screening or during the Screening Period that is positive, as defined below: • Two consecutive positive interferon gamma release assay (IGRA) tests or 2 consecutive indeterminate IGRA tests OR • A purified protein derivative (PPD) skin test ≥5 mm b. A chest X-ray or imaging per local guidelines within 90 days prior to Screening where active or latent pulmonary TB cannot be excluded.
18. 2. Crohn’s disease isolated to the oral cavity, stomach, duodenum, jejunum, or perianal region, without colonic or ileal involvement.
19. 3. Extensive bowel resection (>100 cm), and/or more than 3 resections, and/or known diagnosis of short bowel syndrome.
20. 4. Currently receiving total parenteral nutrition, tube feeding, or a formula diet.
21. 5. Has current evidence of un-resected colonic dysplasia or un-resected adenomatous colonic polyps, stoma, ileostomy, or colostomy at Screening.
22. 6. Has any of the following known complications of CD: • abscess (abdominal or perianal) • impassable fibrotic strictures • symptomatic bowel strictures or obstruction • fulminant colitis • toxic megacolon • intra-abdominal or enterocutaneous fistula.
23. 23. Treatment with cyclosporine, mycophenolate, tacrolimus, thalidomide, or sirolimus within 30 days or 5 half-lives (whichever is shorter) prior to study Day 1.
24. 24. Will require treatment with nonsteroidal anti-inflammatory drugs, including but not limited to ibuprofen, naproxen, indomethacin, and celecoxib, during the study. (However, participants may take aspirin for cardio-protection at a dose indicated per local guidelines but not exceeding 325 mg per day.)
25. 25. Any previous treatment with vedolizumab or other licensed or investigational integrin pathway inhibitors.
26. 26. Experiencing toxicities from prior therapy with Grade >1 within 1 week prior to first dose of study drug.
27. 27. Fecal microbiota transplantation within 90 days prior to Screening.
28. 28. Participant needs to continue treatment with a moderate-to-strong CYP3A inducer or inhibitor and, therefore, will be unable to do a washout period of at least 14 days or 5 half-lives (whichever is longer) prior to study Day 1.
29. 29. Participant needs to continue treatment with an organic anion transporter polypeptide-1B (OATP1B) inhibitor, a P-gp inhibitor, or a narrow therapeutic substrate for P-gp or BCRP, and, therefore, will be unable to do a washout period of at least 14 days or 5 half-lives (whichever is longer) prior to study Day 1.
30. 30. Concurrent participation in any other interventional study.
31. 31. Received any investigational therapy within 30 days or 5 half-lives (whichever is longer) prior to study Day 1.
32. 32. Known allergies/hypersensitivity to any component of the study drug.
33. 33. Previous exposure to MORF-057.
34. 34. Females who are pregnant or lactating or who are planning on becoming pregnant during the course of the study.
35. 35. Current or recent history of alcohol dependence or illicit drug use that may interfere with the participant’s ability to comply with the study procedures.
36. 36. Mental or legal incapacitation or a history of clinically significant psychiatric disorders at the time of the Screening Visit that would impact the ability to participate in the trial according to the Investigator.
37. 37. Unable to attend study visits or comply with procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary efficacy: Proportion of participants with endoscopic response as determined using the Simple Endoscopic Score-CD (SES-CD) at Week 14.

Secondary endpoints 2

1. Secondary efficacy: - Proportion of participants with clinical response as determined using the CDAI at Week 14; - Proportion of participants with clinical remission as determined using the CDAI at Week 14.
2. Safety: Frequencies and proportions of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and TEAEs leading to study drug discontinuation. Change in laboratory parameters, vital signs, and ECG results.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Morphic Therapeutic Inc.

Sponsor organisation

Morphic Therapeutic Inc.

Address

Lilly Corporate Center

City

Indianapolis

Postcode

46285-0001

Country

United States

Scientific contact point

Organisation

Morphic Therapeutic Inc.

Contact name

Lilly Clinical Trials Information Desk

Public contact point

Organisation

Morphic Therapeutic Inc.

Contact name

Lilly Clinical Trials Information Desk

Third parties 14

Locations

12 EU/EEA countries · 80 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 166 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications