Optimization of Golimumab Treatment in Ulcerative Colitis

Colitis, Ulcerative Clinical Trial

Official title:

Optimization of Golimumab Treatment in Ulcerative Colitis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03669029
• Other study ID #: JHV-GOL-2018-01
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: October 1, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: September 2018
• Source: Hospital de Manises
• Contact: Joaquín Hinojosa del Val, MD
• Phone: +34 651184296
• Email: jhinojosad[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, prospective study of dose adjustment of golimumab in patients with ulcerative colitis who will initiate golimumab treatment (naïve to anti-TNF) or after failure (or exposure) to one anti-TNF, which aims to analyze serum golimumab levels and anti- golimumab antibody (ADA) levels during the induction (week 6) and maintenance phases (week 14, 30 and 54) and correlate them with efficacy parameters.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Adult subjects (18 years or older, both sexes and any race) who will be treated with Golimumab according to clinical criteria.

Exclusion Criteria:

• Patients with Crohn's disease or colitis pending classification

• Patients with ileoanal pouch

• Patients with perianal fistulas related to the disease

• Patients with a history of hypersensitivity to golimumab, other murine proteins, or to any of the excipients included in the golimumab datasheet.

• Patients with tuberculosis or other serious infections such as septicemia, abscesses and opportunistic infections.

• Patients with moderate or severe heart failure (NYHA grade III / IV)

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Golimumab 50 mg in patients <80 kg and Golimumab 100 mg in patients >80 kg
Clinical response at week 6,14, 30 and 54 will be correlated to serum golimumab levels and anti-golimumab antibody levels.
• Golimumab treatment optimization.
Golimumab dosing will be optimized in patients without clinical response at week 6.

Locations

Country	Name	City	State
Spain	Joaquín Hinojosa del Val	Manises	Valencia

Sponsors (10)

Lead Sponsor	Collaborator
Hospital de Manises	Hospital Arnau de Vilanova, Hospital Clínico Universitario de Valencia, Hospital de Sagunt, Hospital General Universitario de Alicante, Hospital Provincial de Castellon, Hospital Universitario Doctor Peset, Hospital Universitario La Fe, Merck Sharp & Dohme Corp., Valencia University General Hospital

Country where clinical trial is conducted

Spain, 

References & Publications (11)

Adedokun OJ, Xu Z, Marano CW, Strauss R, Zhang H, Johanns J, Zhou H, Davis HM, Reinisch W, Feagan BG, Rutgeerts P, Sandborn WJ. Pharmacokinetics and Exposure-response Relationship of Golimumab in Patients with Moderately-to-Severely Active Ulcerative Colitis: Results from Phase 2/3 PURSUIT Induction and Maintenance Studies. J Crohns Colitis. 2017 Jan;11(1):35-46. doi: 10.1093/ecco-jcc/jjw133. Epub 2016 Jul 20. — View Citation

Berends S, Strik A, van Egmond P, Brandse H, Mathôt R,D`Haens G, Löwenberg M. Pharmacokinetics of golimumab in patients with moderate tosevere ulcerative colitis. J Crohn´s Colitis 2016; 10 (suppl 1):s424 AP637

Dostalek M, Gardner I, Gurbaxani BM, Rose RH, Chetty M. Pharmacokinetics, pharmacodynamics and physiologically-based pharmacokinetic modelling of monoclonal antibodies. Clin Pharmacokinet. 2013 Feb;52(2):83-124. doi: 10.1007/s40262-012-0027-4. Review. — View Citation

Fasanmade AA, Adedokun OJ, Blank M, Zhou H, Davis HM. Pharmacokinetic properties of infliximab in children and adults with Crohn's disease: a retrospective analysis of data from 2 phase III clinical trials. Clin Ther. 2011 Jul;33(7):946-64. doi: 10.1016/j.clinthera.2011.06.002. Epub 2011 Jul 7. — View Citation

Fasanmade AA, Adedokun OJ, Ford J, Hernandez D, Johanns J, Hu C, Davis HM, Zhou H. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Clin Pharmacol. 2009 Dec;65(12):1211-28. doi: 10.1007/s00228-009-0718-4. Epub 2009 Sep 16. — View Citation

Hutas G. Berends S, Strik A, van Egmond P, Brandse H, Mathôt R,D`Haens G, Löwenberg M. Pharmacokinetics of golimumab in patients with moderate tosevere ulcerative colitis. J Crohn´s Colitis 2016; 10 (suppl 1):s424 AP637

Ordás I, Mould DR, Feagan BG, Sandborn WJ. Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther. 2012 Apr;91(4):635-46. doi: 10.1038/clpt.2011.328. Epub 2012 Feb 22. Review. — View Citation

Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel JF, Reinisch W, Gibson PR, Collins J, Järnerot G, Hibi T, Rutgeerts P; PURSUIT-SC Study Group. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014 Jan;146(1):85-95; quiz e14-5. doi: 10.1053/j.gastro.2013.05.048. Epub 2013 Jun 2. — View Citation

Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel JF, Reinisch W, Gibson PR, Collins J, Järnerot G, Rutgeerts P; PURSUIT-Maintenance Study Group. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014 Jan;146(1):96-109.e1. doi: 10.1053/j.gastro.2013.06.010. Epub 2013 Jun 14. — View Citation

Steenholdt C, Al-khalaf M, Brynskov J, Bendtzen K, Thomsen OØ, Ainsworth MA. Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2012 Dec;18(12):2209-17. doi: 10.1002/ibd.22910. Epub 2012 Feb 16. — View Citation

Vande Casteele N, Ballet V, Van Assche G, Rutgeerts P, Vermeire S, Gils A. Early serial trough and antidrug antibody level measurements predict clinical outcome of infliximab and adalimumab treatment. Gut. 2012 Feb;61(2):321; author reply 322. doi: 10.1136/gut.2010.236869. Epub 2011 Feb 17. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between serum Golimumab levels and clinical response.	Serum Golimumab levels will be measured and clinical activity evaluation will be assessed according to the partial Mayo score and biochemical parameters such as C-reactive protein and calprotectin.	Week 6.
Primary	Correlation between anti-Golimumab antibody levels and clinical response.	Anti-golimumab antibody levels will be measure and clinical activity evaluation will be performed according to the partial Mayo score and biochemical parameters such as C-reactive protein and calprotectin.	Week 6.
Secondary	Treatment optimization outcome.	Analyze the percentage of non-responder patients or patients with partial response at week 6 who achieve response/remission at week 14 after treatment optimization.	Week 14
Secondary	Correlation between mucosal healing and serum Golimumab levels.	An endoscopy will be performed at the end of the treatment and serum Golimumab levels will be measured.	Week 54
Secondary	Identification of cut-off values of serum golimumab concentration	Identify useful cut-off values of serum golimumab concentration for use in ulcerative colitis practice.	Week 6
Secondary	Correlation between mucosal healing and anti-Golimumab antibody levels.	An endoscopy will be performed at the end of the treatment and anti-Golimumab antibody levels will be measured.	Week 54