Study to Evaluate the Clinical Activity and Safety of Oral NX-13 in Participants with Moderate to Severe Ulcerative Colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Landos Biopharma 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

4 Dec 2023 → 30 May 2025

Decision date (initial)

2023-08-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Landos Biopharma Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Pharmacokinetic, Safety

To assess the clinical activity of oral NX-13 vs placebo

Secondary objectives 7

1. Safety and tolerability
2. Clinical remission
3. Clinical response
4. Endoscopic response
5. Endoscopic remission
6. Endoscopic-histologic mucosal improvement
7. Symptomatic remission

Conditions and MedDRA coding

Ulcerative Colitis

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 18 to 75 years of age at time of informed consent
2. Able to give informed consent, attend, and comply with study visits and e-diaries
3. Diagnosed with UC ≥ 3 months prior to screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence. The endoscopy and histology report should be present in source documents; however, if not available, the screening endoscopy and histology report may serve as such.
4. Received a surveillance colonoscopy (performed according to local standard) within 12 months prior to the planned randomization date to rule out dysplasia in individuals with pancolitis > 8 years duration or individuals with left sided colitis > 12 years duration. Individuals without a surveillance colonoscopy within the prior 12 months will have a colonoscopy at screening (i.e., in place of the screening proctosigmoidoscopy). Any adenomatous polyps must be removed according to routine practice prior to the study participant’s first dose of investigational product.
5. Moderate to severe disease activity, characterized by all of the following (see Section 7.3.1 for details): • MMS ≥ 5 defined as follows: • ES ≥ 2 within 14 days prior to randomization • RBS ≥ 1
6. An inadequate response to, loss of response to, or intolerance of at least 1 of the following therapies, as defined below (see Section 12.9 for details): Conventional therapy classes: • Oral 5-ASA compounds plus systemic glucocorticosteroids/glucocorticoids • Systemic glucocorticosteroids/glucocorticoids • Thiopurines Biologic therapy classes: • Anti-TNF monoclonal antibodies or biosimilars • Anti-integrin monoclonal antibodies • Anti-IL-12/23 monoclonal antibodies Advanced therapy classes: • JAK inhibitors • S1P receptor modulators
7. Eligible male participants must either: • Be surgically sterile (i.e., vasectomy) for ≥ 3 months (≥ 90 days) before screening; or • Agree to the following, from the time of randomization until at least 30 days after last dose of investigational product: o Agree to use a condom with spermicide when sexually active with a female partner who was not using a highly effective method of birth control o Agree not to participate in a conception process (i.e., active attempt to impregnate, sperm donation, or in vitro fertilization)
8. Eligible female participants must be: • Nonpregnant, evidenced by a urine dipstick pregnancy test within 24 hours prior to randomization, and • Nonlactating
9. Eligible female participants of non-childbearing potential must be surgically sterile or postmenopausal (defined as ≥ 1 year without menses). • Women must be surgically sterile for at least 6 months before screening as confirmed by medical history. Surgical procedures are tubal ligation performed laparoscopically, hysterectomy, and/or bilateral oophorectomy; or other procedures if sponsor agrees. • A postmenopausal state is defined as no menses for ≥ 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy.
10. Women of childbearing potential (WOCBP) must: • Agree to use birth control methods that are considered highly effective: o Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal o Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable o Intrauterine device (IUD) o Intrauterine hormone-releasing system (IUS) o Bilateral tubal occlusion o Vasectomized partner o Sexual abstinence Note: Contraceptive measures such as Plan B (used after unprotected sex) are not considered highly effective methods of contraception for this study • Agree not to participate in a conception process (i.e., active attempt to become pregnant, egg donation, in vitro fertilization) for at least 30 days after the last dose of investigational product

Exclusion criteria 40

1. Severe extensive colitis as evidenced by: • Physician judgment that the participant is likely to require hospitalization for medical care or surgical intervention of any kind for UC (e.g., colectomy) within the 12 weeks after randomization • Current evidence of fulminant colitis, toxic megacolon or recent history (within 6 months prior to screening) of toxic megacolon, or bowel perforation
2. Diagnosis of Crohn’s disease (CD) or indeterminate colitis, or the presence or history of a fistula consistent with CD
3. Inadequate response to an induction course of more than 2 classes of biologics (e.g. TNF alpha, integrin or IL-12/23) approved for UC
4. Diagnosis of microscopic colitis, ischemic colitis, or radiation colitis
5. History of active bacterial, viral, fungal, or mycobacterial infectious colitis requiring oral antibiotic/anti-infective treatment within 4 weeks prior to screening.
6. Infection requiring hospitalization or intravenous (IV) antimicrobial therapy within 8 weeks prior to screening
7. Presence of indefinite dysplasia or UC-associated dysplasia on colonoscopy or FS, or a history of UC-associated dysplasia
8. History of colectomy (total or subtotal), ileoanal pouch, Kock pouch, or ileostomy; or is planning bowel surgery
9. History of spontaneous gastrointestinal (GI) perforation (other than appendicitis or mechanical injury), diverticulitis, or at significantly increased risk of GI perforation per the investigator’s judgment
10. Hospitalization for exacerbation of UC requiring IV steroids (i.e., UC flare) within 12 weeks prior to screening (a single dose of IV steroids is acceptable)
11. Treatment with cyclosporine, tacrolimus, sirolimus, methotrexate, or mycophenolate mofetil within 4 weeks prior to screening.
12. Thiopurine washout is required to be completed within 6 weeks prior to screening.
13. Treatment with a biologic agent (e.g., infliximab, vedolizumab) within 6 weeks or 5 elimination half-lives (whichever is less) prior to screening. For anti-IL-12/23 (p19 or p40 subunits) (e.g., ustekinumab) a total of 12 weeks (6 weeks prior to screening and 6 weeks of screening) or 5 elimination half-lives (whichever is less) of washout.
14. Treatment with an advanced oral UC therapy (e.g., JAK inhibitor, S1P modulator) within 4 weeks prior to screening
15. Treatment with IV glucocorticosteroids/glucocorticoids, rectal glucocorticosteroids/ glucocorticoids, rectal or topical 5-ASA, or enema within 2 weeks prior to screening
16. Treatment with oral prednisone at a daily dose of > 20 mg (or equivalent) or active oral glucocorticosteroids/ glucocorticoids , e.g., budesonide at a daily dose of > 9 mg or equivalent, within 30 days prior to screening. If receiving systemically active oral glucocorticosteroids/ glucocorticoids , must be on a stable dose for at least 14 days prior to screening.
17. Confirmed or suspected infection of the intestinal tract, including positive Clostridioides difficile stool test at screening
18. Have acute or chronic hepatitis B infection or test positive for hepatitis B virus (HBV) at screening
19. Have current hepatitis C infection or test positive for hepatitis C virus (HCV) at screening
20. Have known infection with human immunodeficiency virus as confirmed by medical history
21. Live virus vaccination within 4 weeks prior to randomization (Note: no currently available vaccine for SARS-CoV-2 is a live virus vaccine)
22. Fecal microbial transplantation within 30 days prior to screening
23. Known primary or secondary immunodeficiency
24. Previously received stem cell transplantation
25. Has been a previous recipient of an organ transplant, which requires continued immunosuppression
26. Any surgical procedure requiring general anesthesia within 4 weeks prior to randomization, or planned elective surgery during the study
27. History of malignant neoplasms or carcinoma within 5 years prior to screening (except basal cell and in situ squamous cell carcinomas of the skin that have been fully excised and resolved)
28. Requirement for regular dosing of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) or inducers (e.g., rifampin, phenytoin, carbamazepine) or CYP2C19 inhibitors (e.g., fluconazole, fluoxetine, fluvoxamine, ticlopidine) or inducers (e.g., rifampin).
29. Current or recent history of alcohol dependence or recreational drug use that, in the opinion of the investigator, may interfere with the individual’s ability to comply with the study procedures
30. Mental or legal incapacitation at the time of screening or a history of clinically significant psychiatric disorders that would impact the individual’s ability to participate in the study, according to the investigator
31. Any concurrent clinically significant medical condition that, in the judgment of the investigator, may pose an unacceptable risk to the participant, including any known hypersensitivity to the drug product or any of its excipients
32. Participants with evidence of active or latent infection with Mycobacterium tuberculosis (TB) or participants with this history who have not completed a generally accepted full course of treatment (with completion of this treatment at least 6 months prior to start of screening) are excluded. All other participants must have either the Mantoux (purified protein derivative [PPD]) tuberculin skin test or interferon gamma release assay (IGRA) performed. See Section 12.7 for details.
33. Unable to comply with study activities (e.g., swallow 3 whole tablets per day without crushing, breaking, or chewing)
34. Concurrent participation in any other investigational study, or individuals who have received any investigational therapy within 4 weeks or 5 elimination half-lives (whichever is longer) prior to screening
35. Women who are pregnant, breastfeeding, or contemplating pregnancy, from the time of informed consent until at least 30 days after the last dose of investigational product.
36. Estimated absolute glomerular filtration rate of < 30 mL/minute
37. Liver transaminases (ALT, AST) > 1.5× ULN at screening
38. Total bilirubin > 1.5× ULN at screening, or > 2.0× ULN for individuals with Gilbert’s syndrome
39. Hemoglobin < 9g/dL (< 5.6 mmol/L) at screening
40. Individuals who are investigational site staff members or relatives of those site staff members or are Sponsor or CRO employees directly involved in the conduct of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in Modified Mayo Score (MMS) at Week 12

Secondary endpoints 7

1. Safety and tolerability - Proportion of participants with TEAEs in induction period - Proportion of participants with SAEs in induction period - Change from baseline in clinical laboratory results, vital signs, and ECGs over time in induction period
2. Clinical remission - Proportion of participants with MMS ≤2 at Week 12
3. Clinical response - Proportion of participants with ≥2 points and ≥30% decrease from baseline in MMS with ≥1 point decrease in rectal bleeding subscore RBS or RBS ≤1 at Week 12
4. Endoscopic response - Proportion of participants with endoscopic subscore ES ≤1 at Week 12
5. Endoscopic remission - Proportion of participants with endoscopic subscore ES = 0 at Week 12
6. Endoscopic-histologic mucosal improvement - Proportion of participants with ES ≤1 and Geboes score <2.0 at Week 12
7. Symptomatic remission - Proportion of participants with RBS = 0 and (i) stool frequency subscore SFS = 0 or (ii) SFS = 1 with baseline SFS ≥2, at Week 12

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Landos Biopharma Inc.

Sponsor organisation

Landos Biopharma Inc.

Address

4727 Valley View Boulevard Northwest

City

Roanoke

Postcode

24012-2000

Country

United States

Scientific contact point

Organisation

Landos Biopharma Inc.

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

Landos Biopharma Inc.

Contact name

Global Clinical Trials Helpdesk

Third parties 7

Locations

3 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 26 files

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

Application history

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