GO-COLITIS: Golimumab Utilization and Impact on Ulcerative Colitis (MK-8259-032)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02092285
• Collaborator: (none)
• Enrollment: 205
• Location: 1
• Arm: 1
• Actual Duration (Months): 24.5
• Patients Per Site Per Month: 8.4

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of golimumab in maintaining a clinical response in participants with moderate-to-severe ulcerative colitis.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Golimumab	Phase 4

Detailed Description

This study consists of a 1 week screening period, a 54 week treatment period, and a 12 week follow-up period, requiring a total of 7 trial site visits: Visit 1(screening visit, Week -1), Visit 2 (enrollment visit, Day 0), Visit 3 (Week 2), Visit 4 (Week 6), Visit 5 (Week 30) and Visit 6 (Week 54) and Visit 7 (follow-up visit, Week 66).

Study Design

• Study Type: Interventional
• Actual Enrollment: 205 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Golimumab: A Phase 4, UK, Open Label, Single Arm Study on Its Utilization and Impact in Ulcerative Colitis
• Actual Study Start Date: May 9, 2014
• Actual Primary Completion Date: May 25, 2016
• Actual Study Completion Date: May 25, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Golimumab The first induction dose of subcutaneous (SC) golimumab 200 mg was administered at Day 0. The second induction dose of SC golimumab 100 mg was administered two weeks later at Week 2. Responders at Week 6 received a maintenance dose of golimumab (50 mg for participants with a body weight <80 kg or 100 mg for participants with a body weight ≥80 kg) every 4 weeks during the Maintenance Phase for 48 weeks, yielding a total of 54 weeks treatment.

Drug: Golimumab; 50mg or 100mg solution for injection; subcutaneous injection; Other Names: Simponi®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Meeting Partial Mayo Score Response Criteria Through Week 54 [Baseline (Week 0), Week 6, Week 30, Week 54]

   The Partial Mayo Score (Mayo Score without endoscopy) measures severity of ulcerative colitis. Three sub-scores for stool frequency, rectal bleeding, and physician's global assessment are each graded from 0 to 3 with higher scores indicating more severe disease. Individual sub-scores are then summed to provide the total score ranging from 0 (normal or inactive disease) to 9 (severe disease). Clinical response is defined as a decrease in PMS of ≥2 points and ≥30% from baseline, plus either a decrease in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1. In this outcome measure, the percentage of participants starting treatment at the start of the Induction Phase (Baseline) who obtained clinical response by the end of the Induction Phase (i.e., by Week 6) and maintained clinical response through Week 54 (i.e., had positive clinical responses at both Weeks 30 and 54) are estimated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of ulcerative colitis for at least 3 months with moderate-to-severe disease at enrollment.

• Has a rectal bleeding subscore of 1 or more at baseline.

• No evidence of active, or latent, or inadequately treated infection with Mycobacterium tuberculosis (TB).

• Must be eligible to start golimumab treatment according to the summary of product characteristics.

• Must be naïve to anti-tumor necrosis factor (anti-TNF) therapy.

• Women of childbearing potential or men capable of fathering children must agree to use adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implant, surgical sterilization).

• Women of childbearing potential must test negative for pregnancy at screening.

• Any prior azathioprine / 6-mercaptopurine use was initiated at least 12 weeks prior to enrollment with either stable dosing or discontinued treatment for the 4 weeks immediately prior to enrollment.

Exclusion Criteria:

• Clinical signs of ischaemic colitis, fulminant colitis or toxic megacolon.

• Has evidence of pathogenic bowel infection.

• Has a diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn's disease.

• Has had surgery as a treatment for ulcerative colitis, or is likely to require surgery.

• Has ulcerative colitis which is confined to a proctitis (distal 15 cm or less).

• Has a current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.

• Has a current immunization with any live virus vaccine or history of immunization with any live virus vaccine within 3 months of baseline.

• Pregnant or lactating, or planning pregnancy while enrolled in the study.

• Has received agents that deplete B or T cells (eg, rituximab or alemtuzumab) within 12 months prior to study inclusion, or continue to manifest depletion of B or T cells more than 12 months after completion of therapy with lymphocyte-depleting agents.

• Has received cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 8 weeks prior to study inclusion.

• Has used any investigational drugs within 30 days of Screening.

• Has a known hypersensitivity to human immunoglobulin proteins or other components of golimumab.

• Has received methotrexate within 12 weeks prior to enrollment

• Has received rectal corticosteroids or rectal 5-aminosalicylic acid (5-ASA) compounds within 2 weeks prior to enrollment (may be commenced if required after Week 6 in the study)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Merck Sharp & Dohme Ltd.	Hoddesdon		United Kingdom

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02092285
• Other Study ID Numbers: 8259-032; 2013-004583-56
• First Posted: Mar 20, 2014
• Last Update Posted: Mar 15, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Golimumab

Study Results

Participant Flow

Pre-assignment Detail	A total of 225 participants were screened; 205 participants started treatment after meeting eligibility criteria.

Arm/Group Title	Golimumab
Arm/Group Description	The first induction dose of subcutaneous (SC) golimumab 200 mg was administered at Day 0. The second induction dose of SC golimumab 100 mg was administered two weeks later at Week 2. Responders at Week 6 received a maintenance dose of golimumab (50 mg for participants with a body weight <80 kg or 100 mg for participants with a body weight ≥80 kg) every 4 weeks during the Maintenance Phase for 48 weeks, yielding a total of 54 weeks treatment.
Period Title: Induction Phase
STARTED	205
COMPLETED	170
NOT COMPLETED	35
Period Title: Induction Phase
STARTED	170
COMPLETED	60
NOT COMPLETED	110

Baseline Characteristics

Arm/Group Title	Golimumab
Arm/Group Description	The first induction dose of SC golimumab 200 mg was administered at Day 0. The second induction dose of SC golimumab 100 mg was administered two weeks later at Week 2. Responders at Week 6 received a maintenance dose of golimumab (50 mg for participants with a body weight <80 kg or 100 mg for participants with a body weight ≥80 kg) every 4 weeks during the Maintenance Phase for 48 weeks, yielding a total of 54 weeks treatment.
Overall Participants	205
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.3 (15.09)
Age, Customized (Number) [Number]
Adolescents (12-17 years)	3 1.5%
Adults (between 18 and 64 years)	184 89.8%
From 65 to 84 years	18 8.8%
Sex: Female, Male (Count of Participants)
Female	82 40%
Male	123 60%
Partial Mayo Score (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	6.4 (1.40)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Meeting Partial Mayo Score Response Criteria Through Week 54
Description	The Partial Mayo Score (Mayo Score without endoscopy) measures severity of ulcerative colitis. Three sub-scores for stool frequency, rectal bleeding, and physician's global assessment are each graded from 0 to 3 with higher scores indicating more severe disease. Individual sub-scores are then summed to provide the total score ranging from 0 (normal or inactive disease) to 9 (severe disease). Clinical response is defined as a decrease in PMS of ≥2 points and ≥30% from baseline, plus either a decrease in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1. In this outcome measure, the percentage of participants starting treatment at the start of the Induction Phase (Baseline) who obtained clinical response by the end of the Induction Phase (i.e., by Week 6) and maintained clinical response through Week 54 (i.e., had positive clinical responses at both Weeks 30 and 54) are estimated.
Time Frame	Baseline (Week 0), Week 6, Week 30, Week 54

Outcome Measure Data

Analysis Population Description

The analysis population for the evaluation of efficacy during the maintenance period was the Full Analysis Set (FAS205) consisting of participants who received at least 1 dose of golimumab.

Arm/Group Title	Golimumab
Arm/Group Description	The first induction dose of SC golimumab 200 mg was administered at Day 0. The second induction dose of SC golimumab 100 mg was administered two weeks later at Week 2. Responders at Week 6 received a maintenance dose of golimumab (50 mg for participants with a body weight <80 kg or 100 mg for participants with a body weight ≥80 kg) every 4 weeks during the Maintenance Phase for 48 weeks, yielding a total of 54 weeks treatment.
Measure Participants	205
Number (95% Confidence Interval) [Percentage of Participants]	24.9 12.1%

Adverse Events

Time Frame	Up to 66 weeks
Adverse Event Reporting Description	The analysis population for the evaluation of safety was the All Participants as Treated population consisting of any participant who received study medication.
Arm/Group Title	Golimumab
Arm/Group Description	The first induction dose of SC golimumab 200 mg was administered at Day 0. The second induction dose of SC golimumab 100 mg was administered two weeks later at Week 2. Responders at Week 6 received a maintenance dose of golimumab (50 mg for participants with a body weight <80 kg or 100 mg for participants with a body weight ≥80 kg) every 4 weeks during the Maintenance Phase for 48 weeks, yielding a total of 54 weeks treatment.
All Cause Mortality
	Golimumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Golimumab
	Affected / at Risk (%)	# Events
Total	49/205 (23.9%)
Cardiac disorders
BRADYCARDIA	1/205 (0.5%)	1
MYOCARDIAL INFARCTION	1/205 (0.5%)	2
Eye disorders
CORNEAL EROSION	1/205 (0.5%)	1
ULCERATIVE KERATITIS	1/205 (0.5%)	1
Gastrointestinal disorders
ABDOMINAL TENDERNESS	1/205 (0.5%)	1
ANAL FISSURE	1/205 (0.5%)	1
COLITIS	5/205 (2.4%)	6
COLITIS ULCERATIVE	23/205 (11.2%)	23
CONSTIPATION	1/205 (0.5%)	1
PANCREATITIS	1/205 (0.5%)	1
RECTAL FISSURE	1/205 (0.5%)	1
Immune system disorders
ANAPHYLACTIC REACTION	1/205 (0.5%)	1
Infections and infestations
ANAL ABSCESS	1/205 (0.5%)	1
APPENDICITIS	1/205 (0.5%)	1
CLOSTRIDIUM BACTERAEMIA	1/205 (0.5%)	1
DIVERTICULITIS	1/205 (0.5%)	1
LOWER RESPIRATORY TRACT INFECTION	1/205 (0.5%)	1
PNEUMONIA	1/205 (0.5%)	1
RESPIRATORY TRACT INFECTION	1/205 (0.5%)	1
SEPSIS	1/205 (0.5%)	1
WOUND INFECTION	1/205 (0.5%)	1
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE	3/205 (1.5%)	3
GASTROINTESTINAL STOMA COMPLICATION	1/205 (0.5%)	2
POST PROCEDURAL COMPLICATION	1/205 (0.5%)	1
Investigations
INTERNATIONAL NORMALISED RATIO INCREASED	1/205 (0.5%)	1
LIVER FUNCTION TEST ABNORMAL	1/205 (0.5%)	1
Musculoskeletal and connective tissue disorders
BACK PAIN	1/205 (0.5%)	1
BURSITIS	1/205 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PANCREATIC CARCINOMA METASTATIC	1/205 (0.5%)	1
Nervous system disorders
MIGRAINE	1/205 (0.5%)	1
Pregnancy, puerperium and perinatal conditions
ABORTION SPONTANEOUS	1/205 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
EMPHYSEMA	1/205 (0.5%)	1
PULMONARY EMBOLISM	2/205 (1%)	2
Vascular disorders
DEEP VEIN THROMBOSIS	1/205 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Golimumab
	Affected / at Risk (%)	# Events
Total	82/205 (40%)
Gastrointestinal disorders
COLITIS	15/205 (7.3%)	15
COLITIS ULCERATIVE	28/205 (13.7%)	29
NAUSEA	15/205 (7.3%)	15
Infections and infestations
NASOPHARYNGITIS	20/205 (9.8%)	22
Nervous system disorders
HEADACHE	15/205 (7.3%)	18
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN	14/205 (6.8%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Investigator agrees to provide to the Sponsor 45 days prior to submission, review copies of abstracts or manuscripts for publication that report any results of the trial. The Sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation with regards to proprietary information, data accuracy, fairness, and compliance with federal regulations.