Ulcerative Colitis: Efficacy, Safety, and Pharmacokinetics of Upadacitinib in Pediatric Subjects with Moderately to Severely Active Ulcerative Colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abbvie Deutschland GmbH & Co. KG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

14 Nov 2023 → ongoing

Decision date (initial)

2023-10-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

The primary efficacy objective for the open-label induction and double-blind maintenance portion of Study M14-658 (Period 1) is to demonstrate efficacy based on a higher rate of subjects who achieve Adapted Mayo Score (AMS) clinical remission at Week 8, as well as a higher rate of subjects who achieve AMS clinical remission at Week 52 among Week 8 responders per AMS in above specified pediatric subjects based on the intent-to-treat (ITT) population (consisting of all subjects who enrolled into the induction phase; for the induction endpoint) / modified ITT (mITT) population (consisting of all subjects who were randomized into the maintenance phase; for the maintenance endpoint) when compared to external placebo.

Secondary objectives 1

1. The key secondary efficacy objectives for Period 1 are to demonstrate efficacy based on a higher rate of subjects who achieve the ranked secondary endpoints, as specified in Section 3.3, in above specified pediatric subjects based on the ITT population (for induction efficacy) or mITT population (for maintenance efficacy) when compared to external placebo.

Conditions and MedDRA coding

Ulcerative Colitis

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-001741-PIP02-16

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Pediatric male or female subjects 2 to 17 years of age at screening and Baseline visits
2. Eligible subjects must have moderately to severely active UC, defined as an AMS of 5 to 9 points and endoscopy subscore of 2 or 3 (confirmed by central reader) and an inadequate response, loss of response, intolerance, or medical contraindications to corticosteroids, immunosuppressants, and/or biologic therapy.
3. Subject must have total body weight at time of screening and Baseline of ≥ 10 kg.
4. Documented diagnosis of UC prior to Baseline, confirmed by colonoscopy during the screening period, with exclusion of current infection, colonic dysplasia and/or malignancy.
5. Subjects must have discontinued: The biologic agents infliximab and adalimumab, including biosimilars, 2 half-lives prior to Baseline. Any other biologic agent or procedure within 30 days or 5 half-lives prior to Baseline, whichever is longer, and no longer be currently enrolled in another interventional clinical study. Note: No minimum washout prior to Baseline is required for any biologic therapy if there is proper documentation of an undetectable drug level measured by a commercially available assay.

Exclusion criteria 7

1. Subject have had previous exposure to JAK inhibitors (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib).
2. Subject have a history of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months. Urine drug screen can be performed at screening, per investigator's discretion.
3. Subject have received fecal microbial transplantation within 30 days prior to Baseline.
4. Subject have current or past history of infection.
5. The investigator has reason to believe that the subject is an unsuitable candidate to participate in the study, receive study drug, or would be placed at risk by participating in the study
6. Subjects have any of the following medical diseases or disorders: a) Disease limited to the rectum (ulcerative proctitis) during the screening endoscopy. b) History of colectomy (total or subtotal), ileoanal pouch, Kock pouch, or ileostomy or planned bowel surgery. c) Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery; d) History of an organ transplant which requires continued immunosuppression; e) History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class; f) History of gastrointestinal (GI) perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment, including history of volvulus and/or intussusception (telescoping of bowels); g) Diagnosis of Crohn's Disease or indeterminant colitis; h) Current diagnosis of fulminant colitis and/or toxic megacolon
7. Principal Exclusion Criteria 6 –(continued) i) Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; subjects with a history of gastric banding/segmentation are not excluded; j) History of malignancy except for successfully treated NMSC or localized carcinoma in situ of the cervix; k) A participant who has had extensive colitis for ≥ 8 years, or disease limited to the left side of the colon for ≥ 12 years, must: a) Have had a full colonoscopy to assess for the presence of dysplasia within 1 year before the first administration of study intervention, or b) Have a full colonoscopy with surveillance for dysplasia as the Baseline endoscopy during the screening period. Results from these surveillance biopsies must be negative for dysplasia (low-grade, high-grade, or indeterminant) prior to the first administration of study intervention; l) Primary immune deficiency.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Induction: AMS clinical remission at Week 8.
2. Maintenance: AMS clinical remission at Week 52 among Week 8 responders per AMS.

Secondary endpoints 9

1. Achievement of endoscopic improvement (defined as Mayo Endoscopic Score [MES] ≤ 1) at Week 8.
2. Achievement of Partial Mayo Score (PMS) clinical remission (defined as a PMS ≤ 2 and no individual subscore > 1) at Week 8.
3. Achievement of AMS clinical response (defined as decrease in AMS by ≥ 2 points and ≥ 30% from Baseline with a decrease in Rectal Bleeding Subscore [RBS] of ≥ 1 or an absolute RBS of 0 or 1) at Week 8.
4. Achievement of endoscopic improvement at Week 52 among Week 8 responders per AMS.
5. Achievement of PMS clinical remission at Week 52 among Week 8 responders per AMS.
6. Achievement of AMS clinical response at Week 52 among Week 8 responders per AMS.
7. Achievement of PMS clinical response (defined as decrease in PMS by ≥ 2 points and ≥ 30% from Baseline with a decrease in RBS ≥ 1 or an absolute RBS of 0 or 1) at Week 52 among Week 8 clinical responders per AMS.
8. Ability to discontinue corticosteroids prior to Week 52 and achievement of AMS clinical remission (achievement of CS-free AMS clinical remission) at Week 52 among Week 8 responders per AMS.
9. Achievement of AMS clinical remission at Week 52 among Week 8 remitters per AMS.

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abbvie Deutschland GmbH & Co. KG

Sponsor organisation

Abbvie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 8

Locations

11 EU/EEA countries · 25 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

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 161 files

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

Application history

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