An Investigation of Oral BT051 in Subjects With Moderately to Severely Active Ulcerative Colitis (UC)

NCT05084261 | Completed Phase 1 FDA Drug

• 1 other identifier: BT051-1-002
• Study Type: interventional
• Target: 24
• Locations: 4 countries
• Sites: 6

Brief Summary

This is a randomised, double-blind, placebo-controlled study to assess the safety and tolerability of multiple ascending doses of BT051 in subjects with moderately to severely active ulcerative colitis. Subjects will be randomised using a 3 active:1 placebo ratio to 3 ascending dose cohorts of 8 subjects and will be dosed daily for 28 days. The 3 initial dose levels will be 200 mg, 800 mg and 3200 mg per day. Progression to the next cohort will be based on the safety and tolerability of the previous cohort.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects experiencing treatment-emergent adverse events (TEAEs)

  Proportion of subjects experiencing a TEAE will be summarized using the MedDRA system organ class and preferred term

  Baseline to Day 58

• Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects observed with a change from baseline in physical examinations, clinical laboratory tests, vital signs, and electrocardiograms (ECG)

  Proportion of subjects with a change from baseline from normal to abnormal in physical examinations, clinical laboratory tests, vital signs, and ECGs will be summarized

  Baseline to Day 58

Secondary Outcomes (13)

• Clinical response defined as a decrease in complete Mayo Score ≥3 points and ≥30% from baseline with a concomitant decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1 point

  Baseline to Day 28

• Clinical response defined as a decrease in complete Mayo Score ≥2 points and ≥30% from baseline with a concomitant decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1

  Baseline to Day 28

• Remission defined as a complete Mayo Score ≤2 points with no subscore >1 point at Day 28

  Baseline to Day 28

• Remission defined as a partial Mayo Score ≤2 points with no subscore >1 point at Days 14 and 28

  Baseline to Days 14 and 28

• Remission according to the adapted Mayo Score without the physician's global assessment, defined as a stool frequency subscore ≤1 point, rectal bleeding subscore of 0, and endoscopic subscore ≤1 point

  Baseline to Day 28

Other Outcomes (5)

• Maximum observed concentration (Cmax) in whole blood

  Baseline to Day 28

• Time to maximum observed concentration (Tmax) in whole blood

  Baseline to Day 28

• Area Under the Concentration-Time Curve (AUC) in whole blood

  Baseline to Day 28

Study Arms (4)

BT051 200 mg

EXPERIMENTAL

Participants will receive oral BT051 200 mg once daily for 28 days.

Drug: BT051 200 mg

BT051 800 mg

EXPERIMENTAL

Participants will receive oral BT051 800 mg once daily for 28 days.

Drug: BT051 800 mg

BT051 3200 mg

EXPERIMENTAL

Participants will receive oral BT051 3200 mg once daily for 28 days.

Drug: BT051 3200 mg

Placebo

PLACEBO COMPARATOR

Participants will receive oral Placebo to match BT051 once daily for 28 days.

Drug: Matching Placebo

Interventions

BT051 200 mg DRUG

Oral BT051 200 mg once daily for 28 days.

Also known as: ADS051

BT051 200 mg

BT051 800 mg DRUG

Oral BT051 800 mg once daily for 28 days.

Also known as: ADS051

BT051 800 mg

BT051 3200 mg DRUG

Oral BT051 3200 mg once daily for 28 days.

Also known as: ADS051

BT051 3200 mg

Matching Placebo DRUG

Placebo Matching BT051

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written documentation of informed consent to participate in the study.
• Male or female aged 18 to 75 years.
• Subjects with a confirmed diagnosis of UC of at least 3 months' disease duration prior to Screening (diagnosis established by endoscopy and histology).
• Moderately to severely active UC, defined as a Mayo Score ≥6 points with a rectal bleeding subscore ≥1 point, a stool frequency subscore ≥1 point, and moderate to severe disease on endoscopy (Mayo endoscopic subscore \[MES\] ≥2 points).
• Subjects treated with stable doses (\>4 weeks) of the following UC treatments prior to randomization: 6-mercaptopurine, azathioprine, sulfasalazine or 5-aminosalicylic acid. Subjects will need to maintain stable doses of these drugs for at least 4 weeks during study treatment and an additional 7 days of follow-up.
• Subjects treated with oral corticosteroids will be eligible if the dose is ≤20 mg/day prednisone (≤9 mg/day budesonide) or equivalent. The corticosteroid therapy will have to be stable for at least 2 weeks prior to the Screening sigmoidoscopy, throughout study treatment and an additional 7 days of follow-up.
• Colonoscopy within the past 1 year to exclude adenomas, dysplasia, and colon cancer for subjects with 1/3 of colon involved and 8 years of disease; those without a colonoscopy in the past year may use the Screening colonoscopy to confirm eligibility.
• Female subjects must be surgically sterile, postmenopausal (i.e., no menses for at least 2 years or documented by follicle stimulating hormone), or if of child-bearing potential must have a negative pregnancy test and must be willing to use a highly effective form of contraceptive through 30 days after the last dose of study drug. The following are considered highly effective contraceptives: combined and progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal, injectable, implantable), intrauterine device/hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or abstinence. Abstinence should only be used as a contraceptive method if it is in line with the subject's usual and preferred lifestyle. Periodic abstinence (calendar, symptothermal, post ovulation methods) is not an acceptable method of contraception.
• Male subjects must be surgically sterile, abstinent, agree to use an appropriate contraception method (i.e., condom), or have a female sexual partner who is surgically sterile, postmenopausal, or using a highly effective form of contraceptive as noted above through 30 days after the last dose of study drug. Abstinence should only be used as a contraceptive method if it is in line with the subject's usual and preferred lifestyle.

You may not qualify if:

• Any clinically significant disease: renal, hepatic, neurological, cardiovascular, pulmonary, endocrinology, psychiatric, hematologic, urologic, or other acute or chronic disease that in the opinion of the Investigator would not make the subject a suitable candidate for this study.
• Subjects with planned hospitalization or surgery during the course of the study.
• Female subjects who have a positive pregnancy test, are breast feeding, or intend to become pregnant during the course of the study. Male subjects who intend female partner pregnancy during the course of the study.
• Known hypersensitivity to any of the components of BT051 drug product including cyclosporine A and polyethylene glycol.
• Relative to upper limit of normal (ULN):
• Serum bilirubin \>1.5×
• Serum creatinine \>1.5×
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \>2.0×
• International normalized ratio (INR) \>1.5
• Hemoglobin \<8 g/dL
• Cell counts (/μL):
• Platelets \<100,000 or \>800,000
• White blood cells \<3500
• Absolute neutrophil count \<1500
• Systemic antibiotic, antiviral, or anti-fungal therapy within the 2 weeks prior to Screening.

Sponsors & Collaborators

• Adiso Therapeutics: lead

Study Sites (6)

Inland Empire Clinical Trials, LLC

Rialto, California, 92377, United States

Location

I.H.S. Health, LLC

Kissimmee, Florida, 34741, United States

Location

Research Institute of Clinical Medicine Todua Clinic

Tbilisi, Georgia

Location

Republican Clinical Hospital - Timofei Mosneaga

Chisinau, Moldova

Location

WIP Warsaw IBD Point

Warsaw, Poland

Location

PlanetMed Gastroenterology

Wroclaw, Poland

Location

Related Publications (1)

• Allegretti JR, Cheifetz AS, Dulai PS, Stevens AC, Chapas-Reed J, Chesnel L, Dixit B, Farquhar R, Ghahramani P, Miller BW, Murphy CK, Quintas M, Tanase R, Telia T, Wozniak-Stolarska B, Gupta R. Safety, Pharmacokinetics, and Clinical Efficacy of ADS051, a Neutrophil Modulator, in Ulcerative Colitis: Results of a Randomized Phase 1b Trial. Am J Gastroenterol. 2024 Dec 31;120(7):1624-1635. doi: 10.14309/ajg.0000000000003269.

  PMID: 39787364 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Renu Gupta, MD

  Adiso Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: October 19, 2021
• Study Start: November 30, 2021
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

US (2); GE (1); PL (2); MO (1)