Clinical trial NCT06109441: Efficacy/Safety of ALTB-268 in Subjects w/Moderately to Severely Active UC Refractory to Biologics
Official title: Phase 2a, Multicenter, Open-Label Study Evaluating the Efficacy and Safety of ALTB-268 in Subjects With Moderately to Severely Active Ulcerative Colitis Refractory to Biologic Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
Efficacy
Safety
Lead sponsor: AltruBio Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-31
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: ALTB-268-201 is a Phase 2a, multicenter, single arm, multiple-dose, open-label study evaluating the efficacy and safety of ALTB-268 in subjects with moderately to severely active UC. The study consists of a Screening Phase, an Induction Phase, a Maintenance Phase, and an OLE.

Detailed description: ALTB-268-201 is a Phase 2a, multicenter, single arm, multiple-dose, open-label study evaluating the efficacy and safety of ALTB-268 in subjects with moderately to severely active UC.

The study consists of a Screening Phase, an Induction Phase, a Maintenance Phase, and an OLE. Upon successful completion of the Screening Phase, subjects will return to the clinic for their first visit, which must occur within 28 days of the initial Screening Visit. Eligible subjects will be enrolled to receive a SC loading dose of ALTB-268, followed by a weekly maintenance dose of ALTB-268 in the 12-week Induction Study Phase. Participants entering the maintenance study phase will continue to receive the SC dose of ALTB-268 every two weeks, up to week 52. Upon completion of the maintenance study phase, study participants will be asked to return for an end of study visit in approximately 4 weeks unless they continue in an open-label extension (OLE).

Eligibility criteria: Inclusion Criteria:

1. Adult participants 18 to 75 years old, inclusive, at Screening.
2. Willing to provide informed consent and to be compliant with the schedule of study visits and protocol assessments.
3. Diagnosis of UC established at least 12 weeks prior to Screening by standard clinical and endoscopic evidence and corroborated by a histopathology report.
4. Moderately to severely active UC, at the time of Screening, defined as a modified Mayo Score (mMS) of 5-9, inclusive, with an endoscopic subscore of ≥ 2 (from central reading), and a rectal bleeding (RB) subscore of ≥ 1.
5. Evidence of active UC, extending proximal to the rectum with ≥ 15 cm of involved colon.
6. Stable doses of concomitant medications:

   1. Subjects receiving oral corticosteroids for the treatment of UC must be on a stable dose of ≤ 20 mg/day (prednisone or equivalent), or ≤ 9 mg/day budesonide. This dose must be stable from the initial Screening visit until the end of the Induction Phase.
   2. Subjects receiving oral 5-aminosalicylic acid (5-ASA) must be on a stable dose from the initial Screening visit until the end of study.
   3. Subjects receiving immunosuppressants (azathioprine, 6-mercaptopurine \[6-MP\] or methotrexate) must be on a stable dose for 4 weeks prior to Screening until the end of study treatment. Subjects taking methotrexate are also advised to take folic acid 5 mg/week (or equivalent) if there is no contraindication.
   4. Subjects receiving probiotics must be on a stable dose from the initial Screening visit until the end of study.
   5. Subjects receiving an anti-diarrhetic must be on a stable dose for ≥ 2 weeks prior to Screening until the end of study.
7. Previous treatment with one or two advanced therapy that demonstrated an inadequate response and/or loss of response.
8. Negative pregnancy test during Screening and Day 1 (V0) in females of childbearing potential.
9. Females with reproductive potential must be sexually abstinent or be willing to use a highly effective method of contraception from study start to ≥ 3 months after the final dose of the study drug. Highly effective methods of contraception include:

   1. Hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); male partner should use a condom;
   2. Intrauterine device or system; or
   3. Surgical sterilization or partner sterile (must have documented proof).
10. Male subjects must be either surgically sterile (must have documented proof), agree to be sexually abstinent, or use a double-barrier method of birth control (e.g., condom and diaphragm with spermicide, condom with cervical cap and spermicide) from first study drug administration to ≥ 3 months after the final dose administration.
11. Male subjects must agree to refrain from donating sperm from first study drug administration to ≥ 3 months after final dose administration.

Exclusion Criteria:

1. Diagnosis of Crohn's colitis, colitis yet to be classified, ischemic colitis, nonsteroidal anti-inflammatory drug (NSAID)-induced colitis, idiopathic colitis (i.e., colitis not consistent with UC), or radiation-induced colitis.
2. Ulcerative colitis limited to the rectum (ulcerative proctitis).
3. Presence of short bowel syndrome.
4. History of colectomy, or presence of an ileostomy or colostomy.
5. History of, or active colonic mucosal dysplasia.
6. Treatment with any intravenous (IV) corticosteroid or rectal therapy during the Screening period.
7. Treatment with any calcineurin inhibitor (e.g., cyclosporine, tacrolimus) from the initial Screening visit.
8. Treatment with NSAIDs within 4 weeks prior to Screening. Short-term use (\<7 days) of NSAIDs for non-UC related symptoms is allowed.
9. Treatment with tofacitinib or other Janus Kinase (JAK) inhibitors from the initial Screening visit.
10. Treatment with sphingosine-1-phosphate receptor (S1PR) modulators from the initial Screening visit.
11. Biologic therapy within 56 days or 5 half-lives (whichever is longer) prior to Screening. Confirmation of undetectable or non-therapeutic serum levels, as assessed by the Investigator, will allow for eligibility.
12. Tube feeding, defined formula diets, or parenteral alimentation/nutrition within 3 weeks of first dosing.
13. Treatment with oral antibiotics within 4 weeks prior to Screening or IV antibiotics within 8 weeks prior to Screening.
14. Vaccination with a live or live-attenuated vaccine within 4 weeks prior to Screening.
15. History of dysplasia or malignancy in the past 5 years, except completely excised basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
16. 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, or any other severe comorbidity that, in the opinion of the Investigator, could confound the study results or put the subject at unreasonable risk.
17. Significant screening electrocardiogram (ECG) abnormalities, including evidence of acute myocardial infarction, complete left bundle branch block, second-degree heart block, or complete heart block.
18. For males, a QTc interval (Fridericia's correction) of \>450 ms, and for females, a QTc interval (Fridericia's correction) of \>470 ms.
19. Any of following laboratory abnormalities during the Screening period. If values are initially outside prescribed limits, the evaluation may be repeated once within the Screening period to determine eligibility:

    1. Calculated creatinine clearance \< 60 mL/min
    2. Serum transaminases \> 2.0x Upper Limit Normal (ULN)
    3. Alkaline phosphatase (ALP) \> 2.0x ULN
    4. Bilirubin \> 1.5x ULN; does not apply to subjects with Gilbert's Syndrome (Meulengracht Syndrome)
    5. Hemoglobin \< 8g/dL
    6. Platelets \< 75,000/μL
    7. Absolute neutrophil count \< 1,500/ μL
    8. Absolute lymphocyte count \< 800/ μL
20. Human immune deficiency virus (HIV) infection or known HIV-related malignancy.
21. Acute or chronic hepatitis B (HBV) or hepatitis C (HCV), or carrier status. Subjects with anti-HBc (hepatitis B core) antibodies (Ab) but with undetectable anti-HBs (hepatitis B surface) Ab should be excluded.
22. Positive immunoglobulin M (IgM) Ab titers in the presence of negative immunoglobulin G (IgG) Ab titers to Epstein-Barr virus (EBV).
23. Positive stool test for ova or parasites, positive stool culture for pathogens, or positive stool toxin assay for Clostridium difficile at Screening.
24. Active cytomegalovirus (CMV) infection at Screening, as assessed by the Investigator.
25. Positive QuantiFERON® TB test at Screening for latent Mycobacterium tuberculosis (TB) infection. If a QuantiFERON® TB test is indeterminate, the test should be repeated. If the result is again indeterminate, the subject should be excluded.

    Subjects with a history of latent TB infection who received or are receiving an appropriate and documented course of therapy can be included if the screening examination and a chest x-ray performed within 3 months prior to Screening revealed no evidence of current active infection.
26. History of any opportunistic infection within 12 weeks of first dosing.
27. Any current or recent symptoms/signs of infection, except nasopharyngitis, within 4 weeks of first dosing.
28. Cirrhosis or active alcohol abuse, pr the judgment of the Investigator.
29. History of drug abuse according teo the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria within 12 months prior to Screening or a positive drug screening test.
30. Currently breast feeding, or pregnant.
31. Known hypersensitivity or intolerance to ALTB-268 or any of its excipients.
32. Participation in another clinical trial AND having received investigational medication within 30 days or 5 half-lives (whichever is longer) prior to Screening or having used an investigational device treatment within 30 days prior to Screening. Concurrent participation in an observational or long-term follow-up study and not actively receiving an investigational drug or device treatment may be eligible for participation in this study.
33. Inability to comply with the study protocol, in the opinion of the Investigator.

Primary outcomes:
measure: Efficacy - change in mMS
timeFrame: week 12
Secondary outcomes:
measure: Efficacy - clinical response
timeFrame: week 12 and week 52
measure: Efficacy - clinical remission
timeFrame: week 12 and week 52
measure: Efficacy - endoscopic improvement
timeFrame: week 12 and week 52
measure: Efficacy - endoscopic remission
timeFrame: week 12 and week 52
measure: Efficacy - histological remission (RHI)
timeFrame: week 12 and week 52
measure: Efficacy- change from baseline in RHI score
timeFrame: week 12 and week 52
measure: Efficacy - Histological remission (Geboes)
timeFrame: week 12 and week 52
measure: Efficacy - change from baseline in Geboes score
timeFrame: week 12 and week 52
measure: Efficacy -Change from baseline in mMS
timeFrame: week 52
measure: Efficacy - Clinical response and /or clinical remission
timeFrame: week 52
measure: Efficacy - corticosteroid free clinical remission
timeFrame: week 52
measure: Efficacy - corticosteroid free clinical response
timeFrame: week 52
measure: Efficacy - change from baseline in pMS
timeFrame: week 12 and week 52
measure: Efficacy - change in mMS
timeFrame: week 12 and week 52
measure: Efficacy - change in IBDQ score
timeFrame: week 12 and week 52
Other outcomes:
Locations:
city: San Diego
country: United States
facility: San Diego Gastroenterology
state: California
city: Littleton
country: United States
facility: Rocky Mountain Gastroenterology
state: Colorado
city: Miami
country: United States
facility: Gastro Health Research
state: Florida
city: Orlando
country: United States
facility: Digestive and Liver Center of Florida, LLC
state: Florida
city: Tampa
country: United States
facility: Alliance Clinical Research of Tampa, LLC.
state: Florida
city: New Albany
country: United States
facility: Gastro Health Partners Southern Indiana
state: Indiana
city: Louisville
country: United States
facility: Gastro Health Partners Louisville
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC.
state: Louisiana
city: Oxford
country: United States
facility: Gastroenterology Associates of North Mississippi
state: Mississippi
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill Cornell Medical Colllege
state: New York
city: Rochester
country: United States
facility: Gastroenterology Group of Rochester
state: New York
city: Utica
country: United States
facility: Digestive Disease Medicine of Central New York
state: New York
city: Beavercreek
country: United States
facility: Dayton Gastroenterology, LLC
state: Ohio
city: Liberty Township
country: United States
facility: Gastro Health Ohio
state: Ohio
city: Uniontown
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: Greenville
country: United States
facility: Gastroenterology Associates, P.A.
state: South Carolina
city: Garland
country: United States
facility: DHAT / GI Aliance
state: Texas
city: Lubbock
country: United States
facility: Caprock Gastro Reasearch
state: Texas
city: Mansfield
country: United States
facility: GI Alliance
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute LLC
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute
state: Texas
city: Webster
country: United States
facility: GI Alliance
state: Texas
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research
state: Wisconsin
city: Vega Baja
country: Puerto Rico
facility: Wellness Clinical Research, LLC
Study officials:
affiliation: AltruBio Inc.
name: David Lin, MD, PhD
role: STUDY_DIRECTOR
References: