Efficacy and Safety of Rosnilimab in Subjects with Ulcerative Colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Anaptysbio 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

30 Jul 2024 → 8 Jan 2026

Decision date (initial)

2024-04-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AnaptysBio, Inc.

External identifiers

EU CT number

2023-508679-34-00

WHO UTN

U1111-1300-1630

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Pharmacodynamic, Safety, Efficacy

To assess the clinical efficacy of rosnilimab versus placebo in subjects with moderate to severe UC

Secondary objectives 4

1. 1. Safety Objective • To evaluate the safety and tolerability of rosnilimab versus placebo in subjects with moderate to severe UC
2. 2. PK Objectives • To evaluate the PK of rosnilimab in subjects with moderate to severe UC
3. 3. PD Objectives • To evaluate the PD of rosnilimab in subjects with moderate to severe UC
4. 4. Immunogenicity Objective • To evaluate the immunogenicity of rosnilimab in subjects with moderate to severe UC

Conditions and MedDRA coding

Ulcerative Colitis

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Male or female who is ≥18 years
2. 2. Clinical diagnosis of UC for > 90 days prior to Day 1, including appropriate documentation of biopsy results that are consistent with UC, based on the assessment of the Investigator. Note: For subjects with no documented histological confirmation of UC diagnosis or if previous diagnosis is not deemed conclusive, UC diagnosis must be confirmed at time of screening colonoscopy by local histological assessment.
3. 3. Moderate to severe active UC defined as a mMS ≥ 5 with an endoscopy subscore ≥ 2 (based on a central reader review) at Baseline.
4. 5. Surveillance colonoscopy did not detect potential dysplasia or colon cancer performed within 1 year of Day 1
5. 6. Subject has completed at least 3 consecutive or 4 nonconsecutive eDiary entries within 7 days before Day 1 (excluding days during bowel preparation for endoscopy)
6. 4. Subject has a history of an inadequate response, loss of response, or intolerance to any combination of at least 2 UC therapy classes. Note: For this study, UC therapy classes are defined as, but not limited to, [1] aminosalicylates (e.g., sulfasalazine, mesalamine, etc.), [2] corticosteroids, (e.g., prednisone, budesonide, dexamethasone, etc.), [3] immunomodulators(e.g., azathioprine, methotrexate, etc.), [4] calcineurin inhibitors (e.g., cyclosporine, tacrolimus, etc.) , [5] advanced UC therapies (e.g., biologics, JAK inhibitors, oral S1P receptor modulators, etc.)

Exclusion criteria 9

1. 1. Clinical diagnosis of Crohn’s disease, indeterminate colitis, fulminant colitis, and/or toxic megacolon
2. 2. Disease limited to the rectum (within 15 cm from anal verge; ulcerative proctitis) during the Screening endoscopy
3. 3. History of colectomy, ileoanal pouch, Kock pouch, or ileostomy or is planning bowl surgery
4. 4. Prior exposure to a PD-1 or PD-L1 agonist, antagonist, or modulator
5. 5. Clostridioides difficile infection within 30 days before Screening or a positive C. difficile toxin stool assay result at Screening, or infection with other intestinal pathogens within the 30 days before Screening
6. 6. Prior or current gastrointestinal (GI) dysplasia in any biopsy performed before or during the Screening endoscopy
7. 7. Evidence of colonic infection during Screening
8. 8. History of an inadequate response, loss of response, or intolerance to any combination of 4 or more advanced UC therapy classes defined as, but not limited to [1] anti-TNF antibodies (e.g., adalimumab, golimumab, infliximab), [2] anti-IL-12/23 biologics (e.g., ustekinumab, mirikizumab, risankizumab), [3] anti-integrins (e.g., vedolizumab), [4] oral JAK inhibitors (e.g., tofacitinib, upadacitinib), and [5] oral S1P receptor modulators (e.g., ozanimod, etrasimod)
9. 9. Current treatment with any of the following: o Oral corticosteroids equivalent to prednisone > 20 mg per day o Oral corticosteroids equivalent to prednisone ≤ 20 mg per day that have been at a stable dose for < 4 weeks before Day 1 o Immunomodulatory biologic agents (including investigational biologics) received within 8 weeks or 5 half-lives (whichever is longer) before Day 1. o Live or live-attenuated vaccines within 12 weeks before Day 1. o Fecal-microbial transplantation within 30 days prior to Day 1

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary Efficacy Endpoint • Mean change from Baseline in mMS at Week 12

Secondary endpoints 13

1. 1. Secondary Efficacy Endpoints • Proportion of subjects achieving clinical remission (defined as a mMS ≤ 2, with a stool frequency subscore (SFS) ≤ 1, RBS = 0, and endoscopic subscore ≤ 1 without friability) at Week 12
2. 2. Secondary Efficacy Endpoints •Proportion of subjects showing endoscopic improvement (defined as an endoscopy subscore ≤ 1 without friability) at Week 12
3. 3. Secondary Efficacy Endpoints •Proportion of subjects achieving a clinical response (defined as a decrease from Baseline in mMS ≥ 2 points and ≥ 30% with a decrease from Baseline in RBS ≥ 1 point or an absolute RBS ≤ 1) at Week 12
4. 4. Exploratory Efficacy Endpoints • Proportion of subjects achieving endoscopic remission (defined as an endoscopy subscore = 0) at Weeks 12, 24 and 50
5. 5. Exploratory Efficacy Endpoints • Proportion of subjects achieving histologic-endoscopic mucosal improvement (defined as an endoscopic subscore of 0 and a Geboes score ≤2) at Weeks 12, 24 and 50
6. 8. Exploratory Efficacy Endpoints • Mean change from Baseline in the following assessments at each time point indicated in the SoAs (Table 1 and Table 2): o mMS o pmMS o IBDQ o Individual mMS subscores (RBS, SFS, and endoscopy subscore) o Geboes score
7. 9. Safety Endpoints • Incidence, type, and severity of AEs, SAEs, and AEs leading to treatment discontinuation and study withdrawal
8. 10. Safety Endpoints • Change from Baseline in vital signs and clinical laboratory parameters
9. 11. Exploratory PK Endpoints • Mean observed predose (trough) rosnilimab concentration (Ctrough) at each time point indicated in the SoAs (Table 1 and Table 2)
10. 12. Exploratory PD Endpoints • Mean change from Baseline in exploratory biomarkers at each time point indicated in the SoAs (Table 1 and Table 2)
11. 13. Exploratory Immunogenicity Endpoints • Number and percentage of subjects at each time point indicated in the SoAs (Table 1 and Table 2) with confirmed positive ADA status and corresponding titer
12. 6. Exploratory Efficacy Endpoints • Proportion of subjects achieving clinical remission (defined as a mMS ≤ 2, with a stool frequency subscore (SFS) ≤ 1, RBS = 0, and endoscopic subscore ≤ 1 without friability) at Weeks 24 and 50
13. 7. Exploratory Efficacy Endpoints • Proportion of subjects showing endoscopic improvement (defined as an endoscopy subscore ≤ 1 without friability) at Weeks 24 and 50

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Anaptysbio Inc.

Sponsor organisation

Anaptysbio Inc.

Address

10770 Wateridge Circle Suite 210

City

San Diego

Postcode

92121-5801

Country

United States

Scientific contact point

Organisation

Anaptysbio Inc.

Contact name

Giles Hulley

Public contact point

Organisation

Anaptysbio Inc.

Contact name

Giles Hulley

Third parties 12

Locations

10 EU/EEA countries · 63 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 191 files

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

Application history

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