Clinical Trial Results:
A Multicenter, Single Arm, Open-label Study to Investigate the Efficacy and Safety of Ravagalimab (ABBV-323) in Subjects With Moderate to Severe Ulcerative Colitis Who Failed Prior Therapy
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Summary
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EudraCT number |
2018-000930-37 |
Trial protocol |
NL DE GB FR ES HU IT |
Global end of trial date |
10 Jan 2022
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Results information
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Results version number |
v1 |
This version publication date |
25 Jan 2023
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First version publication date |
25 Jan 2023
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
M15-722
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03695185 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AbbVie Deutschland GmbH & Co. KG
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Sponsor organisation address |
AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United States, SL6 4UB
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Public contact |
Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
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Scientific contact |
Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Jan 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jan 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this study is to investigate the efficacy, safety, and tolerability of ravagalimab (ABBV-323) in subjects with moderate to severe ulcerative colitis (UC) who failed prior therapy.
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Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Mar 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 8
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
United States: 7
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Country: Number of subjects enrolled |
Germany: 7
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Spain: 4
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Country: Number of subjects enrolled |
United Kingdom: 6
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Worldwide total number of subjects |
42
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EEA total number of subjects |
27
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
40
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
Total 42 subjects were enrolled in Induction Period to receive ravagalimab 600 mg intravenously(IV) followed by ravagalimab 300 mg subcutaneously(SC) up to Week 12. Those who completed Induction Period and achieved clinical response per partial adapted Mayo score at Week 12 entered Maintenance Period to receive ravagalimab 300 mg SC up to Week 102. | ||||||||||||||
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Period 1
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Period 1 title |
Induction Period (Week 0 to Week 12)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Ravagalimab 600 mg/ 300 mg | ||||||||||||||
Arm description |
Subjects received ravagalimab 600 mg IV at Week 0 followed by ravagalimab 300 mg SC at Weeks 2, 4, 6, 8, and 10 in a 12-week Induction Period. Subjects from double-blind (DB) placebo-controlled (prior to protocol version 4.0 of this study) continued their treatment as randomized in the Induction Period. Subjects who achieved clinical response per partial adapted Mayo score at Week 12 of the Induction Period entered the Maintenance Period to receive ravagalimab 300 mg SC every other week (EOW) from Week 12 through Week 102. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Ravagalimab 600 mg
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Investigational medicinal product code |
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Other name |
ABBV-323
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ravagalimab 600 mg administered by IV infusion.
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Investigational medicinal product name |
Ravagalimab 300 mg
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Investigational medicinal product code |
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Other name |
ABBV-323
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Ravagalimab 300 mg administered by SC injection.
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Period 2
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Period 2 title |
Maintenance Period (Week 12 to Week 102)
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Ravagalimab 600 mg/ 300 mg | ||||||||||||||
Arm description |
Subjects received ravagalimab 600 mg IV at Week 0 followed by ravagalimab 300 mg SC at Weeks 2, 4, 6, 8, and 10 in a 12-week Induction Period. Subjects from DB placebo-controlled (prior to protocol version 4.0 of this study) continued their treatment as randomized in the Induction Period. Subjects who achieved clinical response per partial adapted Mayo score at Week 12 of the Induction Period entered the Maintenance Period to receive ravagalimab 300 mg SC every other week (EOW) from Week 12 through Week 102. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Ravagalimab 600 mg
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Investigational medicinal product code |
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Other name |
ABBV-323
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ravagalimab 600 mg administered by IV infusion.
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Investigational medicinal product name |
Ravagalimab 300 mg
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Investigational medicinal product code |
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Other name |
ABBV-323
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Ravagalimab 300 mg administered by SC injection.
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Baseline characteristics reporting groups
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Reporting group title |
Ravagalimab 600 mg/ 300 mg
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Reporting group description |
Subjects received ravagalimab 600 mg IV at Week 0 followed by ravagalimab 300 mg SC at Weeks 2, 4, 6, 8, and 10 in a 12-week Induction Period. Subjects from double-blind (DB) placebo-controlled (prior to protocol version 4.0 of this study) continued their treatment as randomized in the Induction Period. Subjects who achieved clinical response per partial adapted Mayo score at Week 12 of the Induction Period entered the Maintenance Period to receive ravagalimab 300 mg SC every other week (EOW) from Week 12 through Week 102. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ravagalimab 600 mg/ 300 mg
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Reporting group description |
Subjects received ravagalimab 600 mg IV at Week 0 followed by ravagalimab 300 mg SC at Weeks 2, 4, 6, 8, and 10 in a 12-week Induction Period. Subjects from double-blind (DB) placebo-controlled (prior to protocol version 4.0 of this study) continued their treatment as randomized in the Induction Period. Subjects who achieved clinical response per partial adapted Mayo score at Week 12 of the Induction Period entered the Maintenance Period to receive ravagalimab 300 mg SC every other week (EOW) from Week 12 through Week 102. | ||
Reporting group title |
Ravagalimab 600 mg/ 300 mg
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Reporting group description |
Subjects received ravagalimab 600 mg IV at Week 0 followed by ravagalimab 300 mg SC at Weeks 2, 4, 6, 8, and 10 in a 12-week Induction Period. Subjects from DB placebo-controlled (prior to protocol version 4.0 of this study) continued their treatment as randomized in the Induction Period. Subjects who achieved clinical response per partial adapted Mayo score at Week 12 of the Induction Period entered the Maintenance Period to receive ravagalimab 300 mg SC every other week (EOW) from Week 12 through Week 102. | ||
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End point title |
Percentage of Subjects with Endoscopic Improvement During Induction Period [1] | ||||||||
End point description |
Endoscopic Improvement is defined as Mayo endoscopic subscore of 0 or 1. Mayo endoscopic score is classified as 0=Normal or inactive disease; 1=Mild disease (erythema, decreased vascular pattern); 2=Moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3=Severe disease (spontaneous bleeding, ulceration). Higher score indicates worsening of the disease. Full Analysis Set (FAS) included all enrolled subjects who received at least 1 dose of ravagalimab. The number of responders is calculated based on the total number of subjects and estimated response rate, rounding to a nearest whole integer. Data was reported only for the Induction Period.
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End point type |
Primary
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End point timeframe |
At Week 8
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive data are summarized for this end point per protocol |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Clinical Remission per Adapted Mayo Score During Induction Period | ||||||||
End point description |
Clinical remission per Adapted Mayo score is defined as stool frequency subscore (SFS) <=1, and not greater than baseline, rectal bleeding subscore (RBS) = 0, and endoscopic subscore <=1. Adapted Mayo Score is composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal), Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed), Endoscopic subscore confirmed by central reader, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). Overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. FAS included all enrolled subjects who received at least 1 dose of ravagalimab. Number of responders is calculated based on the total number of subjects and estimated response rate, rounding to nearest whole integer. Data was reported only for the Induction Period.
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End point type |
Secondary
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End point timeframe |
At Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Clinical Response Per Adapted Mayo Score During Induction Period | ||||||||
End point description |
Clinical response per Adapted Mayo score is defined as the decrease from Baseline ≥2 points and ≥30%, PLUS a decrease in RBS ≥1 or an absolute RBS ≤1. The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: SFS, scored from 0 (normal number of stools) to 3 (5 or more stools more than normal); RBS, scored from 0 (no blood seen) to 3 (blood alone passed), Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 with higher scores representing more severe disease. FAS included all enrolled subjects who received at least 1 dose of ravagalimab. The number of responders is calculated based on the total number of subjects and estimated response rate, rounding to a nearest whole integer. Data was reported only for the Induction Period.
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End point type |
Secondary
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End point timeframe |
At Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Clinical Response Per Partial Adapted Mayo Score During Induction Period | ||||||||
End point description |
Clinical response per Partial Adapted Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥1 point and ≥30% from Baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1. The Partial Adapted Mayo Score is a composite score of UC disease activity based on the following 2 subscores: SFS, scored from 0 (normal number of stools) to 3 (5 or more stools more than normal); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Adapted Mayo score ranges from 0 to 6 with higher scores representing more severe disease. FAS included all enrolled subjects who received at least 1 dose of ravagalimab. The number of responders is calculated based on the total number of subjects and estimated response rate, rounding to a nearest whole integer. Data was reported only for the Induction Period.
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End point type |
Secondary
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End point timeframe |
Up to Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Clinical Remission per Full Mayo Score During Induction Period in Subjects With a Full Mayo Score of 6 to 12 at Baseline | ||||||||
End point description |
Clinical Remission per full Mayo score (FMS) is defined as Full Mayo score <=2 with no subscore >1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to the nearest whole integer. FAS included all enrolled subjects who received at least 1 dose of ravagalimab. Subjects analysed are the number of subjects available for analyses. Data was reported only for the Induction Period.
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End point type |
Secondary
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End point timeframe |
At Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Endoscopic Remission During Induction Period | ||||||||
End point description |
Endoscopic remission is defined as Mayo endoscopic subscore = 0. Mayo endoscopic subscore is classified as 0=Normal or inactive disease; 1=Mild disease (erythema, decreased vascular pattern, mild friability); 2=Moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3=Severe disease (spontaneous bleeding, ulceration). Higher score indicates worsening of the disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to the nearest whole integer. FAS included all enrolled subjects who received at least 1 dose of ravagalimab. Data was reported only for the Induction Period.
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End point type |
Secondary
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End point timeframe |
At Week 8
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug up to safety follow up visit (up to approximately 116 weeks)
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Adverse event reporting additional description |
Safety Analysis Set included all subjects who received at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Maintenance Period: Ravagalimab 300 mg
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Reporting group description |
Subjects who achieved clinical response per partial adapted Mayo score at Week 12 of the Induction Period entered the Maintenance Period to receive ravagalimab 300 mg SC EOW from Week 12 through Week 102. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Induction Period: Ravagalimab 600 mg/ 300 mg
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Reporting group description |
Subjects received ravagalimab 600 mg IV at Week 0 followed by ravagalimab 300 mg SC at Weeks 2, 4, 6, 8, and 10 in a 12-week Induction Period. Subjects from DB placebo-controlled (prior to protocol version 4.0 of this study) continued their treatment as randomized in the Induction Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 Aug 2018 |
The following changes were implemented with Amendment 1: -Clarified where dose and duration requirements was specified in the body text. -Highlighted key secondary endpoints and moved the rest to exploratory endpoints. -Rescreening was added. -"Systemic hypersensitivity reactions" was changed to "anaphylaxis," and text was added in regards to the types of tests to be carried out in the event of a suspected anaphylaxis. -Revised text to remove the requirement of additional consent for the use of biopsy samples for biomarker research. -Specified the only samples that are optional are blood samples and where the biopsies are taken from. -Added text to clarify that the initiation and/or increase of oral aminosalicylates, immunomodulators, IV or oral corticosteroids, and/or UC-related antibiotics is prohibited through Week 12 specifically, and that the initiation and/or increase of the aforementioned drugs is permissible after discussion with the AbbVie TA MD starting at Week 12. -Provided more detailed text around timing of Day 1 and subsequent serum ABBV-323 and anti-drug antibody (ADA)/ neutalizing antibody (nAb) collection. |
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13 Feb 2019 |
The following changes were implemented with Amendment 2: -Deleted secondary objectives and updated the overall objective. -Clarified that primary and secondary
endpoints are efficacy endpoints and changed the terminology of "safety assessments" to "safety endpoints". -Updated language regarding optional continuation from the induction period into the maintenance period. -Included text regarding the provision of a separate study drug administration guideline. -Updated Primary Analysis text for clarification. -Revised wording to clarify that the subject must understand all aspects of the study and personally sign the informed consent. -Revised wording to further clarify that sites should avoid administration of two consecutive doses of ABBV-323 sooner than 7 days apart. -Updated text regarding golimumab induction regimen. -Updated the footnote 'Lab assessments will only need to be repeated at Baseline if the time between Screening and Baseline is greater than 14 days, or if the subject's health status has changed to warrant a repeat test'. -Changed steroid tapering after Week 12 and during the Maintenance Period from mandatory to optional. -Updated the biomarker lab activities to indicate the exact parameters that will be analyzed at each visit. |
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29 May 2019 |
The following changes were implemented with Amendment 3: -Changed the study design from randomized, double-blind, placebo-controlled to open-label. |
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06 May 2020 |
The following changes were implemented with Amendment 4: -Expanded the maintenance period by an additional 52 weeks with similar, although reduced study procedures as during Week 12 through Week 52. |
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04 Dec 2020 |
The following changes were implemented with Amendment 5: -Added ustekinumab to approved therapies list for key eligibility criteria. -Removed text from key eligibility criterion requiring open-label (OL) use of tofacitinib if received in a clinical trial. -Clarified endpoint definitions. -Removed discussion of the data monitoring committee (DMC) from the study design. -Clarified text regarding primary and interim analysis and the timing of termination of study enrollment, and explicitly permit additional statistical analysis if needed. -Update eligibility criterion, with details regarding subject eligibility with regards to COVID-19 (coronavirus SARS-CoV-2) infection, to remove requirement for tofacitinib and ustekinumab to have been given in open label fashion if received in a clinical trial, and corrected language on, prohibiting pregnancy and breastfeeding. -Clarified discontinuation of study drug as well as study participation. -Clarified that active tuberculosis (TB) is an adverse event of special interest. -Removed sensitivity analysis for the primary efficacy endpoint. -Added Hepatitis B screening, Hepatitis C screening, HIV test, and SARSCoV-2 molecular test to the list of clinical tests which may be performed during the study. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
