Ulcerative Colitis: Developing Drugs for Treatment | Guideline Explorer

Description

The purpose of this guidance is to help sponsors in the clinical development of drugs to treat adults with ulcerative colitis (UC). This guidance addresses the Food and Drug Administration’s (FDA’s) current recommendations on clinical trials for drugs being developed under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355), section 351 of the Public Health Service Act (42 U.S.C. 262) and 21 CFR parts 312, 314, and 601 for treating UC. Specifically, this guidance addresses FDA’s current thinking about the necessary attributes of clinical trials for drugs being developed for treating UC, including trial population, trial designs, efficacy considerations, and safety assessments.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

4

Gene Therapy

A type of ATMP involving recombinant nucleic acids or viral vectors.

Cellular Therapy

Additional considerations may exist for cellular therapies.

Biologic

Product of biological origin applicable to prevention or treatment of disease.

Therapeutic protein products

Sponsors should consider immunogenicity assessment for these products.

Stakeholders

1

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

1

Clinical Trial

design of malaria treatment trials

Document Types

4

Charter

Sponsors should draft charters that standardize procedures

PRO instrument development proposal

Submission for FDA review to assess concepts relevant to UC

Informed Consent

Process by which a subject voluntarily confirms his or her willingness to participate in a particular trial; Integral feature of the ethical conduct of a trial

Event log

Tool for patients to capture rectal bleeding and stool frequency assessments

Attributes

3

Moderately to severely active UC

Disease state defined by a score of 5 to 9 on the modified Mayo Score.

Noninferiority margin

Justification essential for trials using a noninferiority design

Washout period

period for prior therapies, typically five half-lives

Technical Details

Substances

1

Corticosteroids

Example of a drug with age-specific safety concerns regarding growth velocity.

Testing Methods

6

Endoscopy

Method used to document healed EE and assess primary endpoints

Histopathology

The standard of truth for measuring diagnostic performance.; Typically used as a truth standard for optical imaging drugs.

Colonoscopy

recommended to document disease activity in all involved segments

Patient-reported outcome

A type of COA reported directly by the patient.

Sensitivity analyses

Used to evaluate the robustness of overall survival results

Anchor-based analyses

Based on three different anchor-based analyses conducted using an independent sample

Clinical Concepts

4

Ulcerative Colitis

type of pediatric IBD predominantly restricted to the mucosa of the large intestine; Disease state mentioned in relation to stool frequency assessments.

Clinical Remission

primary endpoint defined as mMS score of 0 to 2

Corticosteroid-free remission

secondary endpoint defined by clinical remission and no corticosteroid exposure

Endoscopic improvement

defined as centrally read endoscopy subscore of 0 or 1

Identified Hazards

Hazards

1

Serious infections

Potential increased risk in the early portion of the trial

Standards & References

Specifications

2

Modified Mayo Score

A composite endpoint consisting of rectal bleeding, stool frequency, and endoscopy subscores.; Composite endpoint consisting of rectal bleeding, stool frequency, and endoscopy subscores

mMS

modified Mayo Score used for enrollment and efficacy

ICH References (1)

ICH E9(R1)

Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Failure to ensure that the investigation was conducted according to the investigational plan

21

Failure to submit an Investigational New Drug application (IND)

9

Failure to obtain informed consent

5

Unapproved new drug

5

Misbranded drug

4

Failed to ensure that the investigation was conducted according to the investigational plan

3

Enrollment of subjects who do not meet eligibility criteria

3

Failure to submit INDs for the conduct of clinical investigations

3

Unlicensed biological product

2

unapproved new drugs

2

Recent Cases

Related Warning Letters (10)

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics