POWER: A Study to Evaluate Efficacy and Safety of Ustekinumab Re-induction Therapy in Participants With Moderately to Severely Active Crohn's Disease

Sponsor

Janssen-Cilag Ltd. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03782376

Collaborator

(none)

215

Enrollment

104

Locations

Arms

51.8

Anticipated Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of this study is to evaluate the efficacy and safety of a single intravenous (IV) re-induction dose of approximately 6 milligram per kilogram (mg/kg) ustekinumab in participants with secondary loss of response (LoR) to subcutaneous (SC) every 8 Weeks (q8w) 90 mg ustekinumab maintenance therapy.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Drug: Ustekinumab approximately 6 mg/kg (IV) Drug: Placebo (SC) Drug: Placebo (IV) Drug: Ustekinumab 90 mg (SC) Group 1 Drug: Ustekinumab 90 mg (SC) Group 2	Phase 3

Detailed Description

This study compares the efficacy and safety of a single weight-tiered based IV re-induction dose of approximately 6 mg/kg ustekinumab versus continuing with regular SC q8w 90 mg ustekinumab administration. It consists of screening (5 weeks); treatment period (Week 0 to 24); and safety follow up visit (20 weeks after last dose). The primary hypothesis is that a single IV re-induction dose of ustekinumab is superior to continuing with regular SC q8w maintenance treatment as measured by clinical response after 16 weeks of treatment. Study assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy, patient-reported outcomes (PROs), laboratory evaluations, biomarkers, review of concomitant medications and adverse events (AEs), and evaluation of serum concentrations of study agent as well as development of antibodies to study agent. All participants will be randomly assigned to receive either ustekinumab IV re-induction or regular SC q8w 90 mg ustekinumab injection at baseline in a double dummy design. No participants will be treated with placebo only.

Study Design

Study Type:

Interventional

Actual Enrollment :

215 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3b, Randomized, Double-blind, Multicenter Study to Evaluate the Safety and Efficacy of Intravenous Re-induction Therapy With Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease

Actual Study Start Date :

Dec 20, 2018

Anticipated Primary Completion Date :

Aug 26, 2022

Anticipated Study Completion Date :

Apr 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: Ustekinumab (IV re-induction) Participants who experience a secondary loss of response (LoR) to 90 mg ustekinumab maintenance treatment, administered subcutaneously every 8 weeks (q8w) will receive a weight-tiered based ustekinumab IV re-induction dose of approximately 6 mg/kg and matching placebo subcutaneously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.	Drug: Ustekinumab approximately 6 mg/kg (IV) Participants will receive ustekinumab approximately 6mg/kg intravenously at Week 0. Other Names: STELARA Drug: Placebo (SC) Participants will receive SC injection of placebo at Week 0. Drug: Ustekinumab 90 mg (SC) Group 1 Participants will receive SC injection of ustekinumab 90 mg at Weeks 8 and 16. Other Names: STELARA
Active Comparator: Group 2: Ustekinumab (Continuous q8w SC maintenance) Participants who experience a secondary LoR to 90 mg ustekinumab maintenance treatment, administered subcutaneously q8w will receive ustekinumab 90 mg subcutaneously and matching placebo intravenously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.	Drug: Placebo (IV) Participants will receive IV infusion of placebo at Week 0. Drug: Ustekinumab 90 mg (SC) Group 2 Participants will receive SC injection of ustekinumab 90 mg at Weeks 0, 8 and 16. Other Names: STELARA

Arm

Intervention/Treatment

Experimental: Group 1: Ustekinumab (IV re-induction)

Participants who experience a secondary loss of response (LoR) to 90 mg ustekinumab maintenance treatment, administered subcutaneously every 8 weeks (q8w) will receive a weight-tiered based ustekinumab IV re-induction dose of approximately 6 mg/kg and matching placebo subcutaneously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.

Drug: Ustekinumab approximately 6 mg/kg (IV)

Participants will receive ustekinumab approximately 6mg/kg intravenously at Week 0.

Other Names:

STELARA

Drug: Placebo (SC)

Participants will receive SC injection of placebo at Week 0.

Drug: Ustekinumab 90 mg (SC) Group 1

Participants will receive SC injection of ustekinumab 90 mg at Weeks 8 and 16.

Other Names:

STELARA

Active Comparator: Group 2: Ustekinumab (Continuous q8w SC maintenance)

Participants who experience a secondary LoR to 90 mg ustekinumab maintenance treatment, administered subcutaneously q8w will receive ustekinumab 90 mg subcutaneously and matching placebo intravenously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.

Drug: Placebo (IV)

Participants will receive IV infusion of placebo at Week 0.

Drug: Ustekinumab 90 mg (SC) Group 2

Participants will receive SC injection of ustekinumab 90 mg at Weeks 0, 8 and 16.

Other Names:

STELARA

Outcome Measures

Primary Outcome Measures

Percentage of Participants with Clinical Response at Week 16 [Week 16]
Percentage of participants with clinical response at Week 16 will be assessed. Clinical response is defined as a greater than or equal to (>=) 100 point reduction from the baseline Crohn's Disease Activity Index (CDAI) score or a CDAI score less than (<) 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). CDAI will be assessed by collecting information on 8 different Crohn's disease-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being). A decrease in CDAI over time indicates improvement in disease activity.

Secondary Outcome Measures

Percentage of Participants with Clinical Remission at Week 16 [Week 16]
Percentage of participants with clinical remission at Week 16 will be assessed. Clinical remission is defined as a CDAI score of < 150 points.
Percentage of Participants with Clinical Response at Week 8 [Week 8]
Percentage of participants with clinical response at Week 8 will be assessed. Clinical response is defined as a >=100 point reduction from the baseline CDAI score or a CDAI score <150 points.
Percentage of Participants with Clinical Remission at Week 8 [Week 8]
Percentage of participants with clinical remission at Week 8 will be assessed. Clinical remission is defined as a CDAI score of < 150 points.
Percentage of Participants with Normalization of CRP at Week 16 [Week 16]
Normalization of C-reactive protein is defined as C-reactive protein (CRP) <=3 milligram/liter (mg/L). Percentage of participants with normalization of CRP will be measured at Week 16 among the participants having abnormal baseline CRP (> 3 mg/L).
Percentage of Participants with Normalization of Fecal Calprotectin Concentration at Week 16 [Week 16]
Percentage of Participants with Normalization of Fecal Calprotectin Concentration (<250 mg/kg) at Week 16 will be assessed. Fecal Calprotectin will be monitored as a sensitive and specific marker measured by assay.
Percentage of Participants with Clinical Remission at Week 24 [Week 24]
Percentage of participants with clinical remission at Week 24 will be assessed. Clinical remission is defined as a CDAI score of < 150 points.
Percentage of Participants with Clinical Response at Week 24 [Week 24]
Percentage of participants with clinical response at Week 24 will be assessed. Clinical response is defined as a >=100 point reduction from the baseline CDAI score or a CDAI score <150 points.
Percentage of Participants with Normalization of CRP at Week 24 [Week 24]
Normalization of C-reactive protein is defined as C-reactive protein (CRP) <=3 milligram/liter (mg/L). Percentage of participants with normalization of CRP will be measured at Week 24 among the participants having abnormal baseline CRP (> 3 mg/L).
Percentage of Participants with Normalization of Fecal Calprotectin Concentration at Week 24 [Week 24]
Percentage of Participants with Normalization of Fecal Calprotectin Concentration (<250 mg/kg) at week 24 will be assessed. Fecal Calprotectin will be monitored as a sensitive and specific marker measured by assay.
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Week 36]
The percentage of participants with at least one adverse event and subcategories of adverse events will be assessed. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Percentage of Participants with Infections and Serious Infections [Up to Week 36]
Percentage of participants with infections and serious infections will be reported.
Number of Participants with Clinical Laboratory Abnormalities [Up to Week 24]
Number of participants with laboratory abnormalities will be reported. Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

A history of Crohn's disease or fistulizing Crohn's disease of at least 3 months' duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
Currently receiving subcutaneous 90 mg every 8 weeks (q8w) ustekinumab maintenance therapy and initially responded to ustekinumab induction therapy, administered according to the local label, followed by secondary loss of response (LoR) to ustekinumab. Secondary LoR to ustekinumab is defined as active disease at study baseline, proven by a Crohn's Disease Activity Index (CDAI) score of greater than or equal to (>=) 220 and <=450 with at least one of the following: Elevated C-reactive protein (CRP) (>3.0 milligram per liter [mg/L]); and/or elevated Fecal calprotectin (fCal) >250 milligram per kilogram [mg/kg]); and/or endoscopy (performed less than or equal to (<=) 3 months before baseline) with evidence of active Crohn's disease, (defined as one or more ulcerations in the ileum and/or colon)
Participants receiving either oral 5-aminosalicylic acid (5-ASA) compounds, oral corticosteroids (for example , prednisone, budesonide) at a prednisone-equivalent dose of <=40 mg/day or <=9 mg/day of budesonide, antibiotics used as the primary treatment of Crohn's disease, or conventional immunomodulators (i.e., azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) are permitted providing the doses indicated are stable before baseline or have been discontinued before baseline within the protocol defined durations

Exclusion Criteria:

Complications of Crohn's disease, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with ustekinumab
Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks before baseline (or 8 weeks before baseline for intra-abdominal abscesses) provided there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified
Any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before baseline
A draining (i.e., functioning) stoma or ostomy
Received ustekinumab intravenous re-induction after the initial weight-tiered-based IV induction dose of ustekinumab
Any known history of shortened frequency of SC dose administration (<q8w) for a secondary loss of response where the participant did not, in the opinion of the treating physician, benefit from the dose interval shortening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego	La Jolla	California	United States	92093
2	Peak Gastroenterology Associates	Colorado Springs	Colorado	United States	80907
3	Florida Research Network, LLC	Gainesville	Florida	United States	32605
4	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
5	Advent Health	Orlando	Florida	United States	32803
6	Florida Hospital Tampa	Tampa	Florida	United States	33613
7	Emory University	Atlanta	Georgia	United States	30322
8	Atlanta Gastroenterology Associates, (AGA) LLC - Emory Saint Joseph's	Atlanta	Georgia	United States	30342-5020
9	Atlanta Gastroenterology Specialists	Suwanee	Georgia	United States	30024
10	University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536
11	Chevy Chase Clinical Research	Chevy Chase	Maryland	United States	20815
12	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
13	University of Mississippi Medical Center	Jackson	Mississippi	United States	39202
14	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
15	Mount Sinai School of Medicine	New York	New York	United States	10029
16	Ohio State University Hospital	Hilliard	Ohio	United States	43026
17	Northshore Gastroenterology Research, LLC	Westlake	Ohio	United States	44145
18	Oklahoma Digestive Disease Specialists	Oklahoma City	Oklahoma	United States	73112
19	Medical University of South Carolina	Charleston	South Carolina	United States	29425
20	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
21	Texas Digestive Disease Consultants	Cedar Park	Texas	United States	78613
22	Baylor College of Medicine	Houston	Texas	United States	77025
23	Houston Methodist Hospital	Houston	Texas	United States	77030-2740
24	Gastroenterology Research of America, LLC	San Antonio	Texas	United States	78229
25	Tyler Research Institute, LLC	Tyler	Texas	United States	75701
26	Virginia Mason Medical Center	Seattle	Washington	United States	98101
27	University of Washington	Seattle	Washington	United States	98195
28	Washington Gastroenterology, PLLC	Tacoma	Washington	United States	98405
29	Krankenhaus der Barmherzigen Brüder	Wien		Austria	1020
30	Medizinische Universität Wien	Wien		Austria	1090
31	Hepato-gastroenterologie HK, s.r.o.	Hradec Kralove		Czechia	500 12
32	Klinicke centrum ISCARE	Praha 9		Czechia	190 00
33	Hôpital Beaujon	Clichy		France	92110
34	CHRU de Lille - Hôpital Claude Huriez	Lille		France	59037
35	CHRU Montpellier - Hopital Saint-Eloi	Montpellier		France	34295
36	CHU Hôpital Saint Antoine	Paris cedex 12		France	75571
37	Hospices Civils de Lyon HCL	Pierre Bénite		France	69495
38	CHRU Hôpital de Pontchaillou	Rennes		France	35033
39	CHU de Nancy_ Hôpital Brabois	Vandoeuvre-les-Nancy		France	54511
40	Klinikum Augsburg	Augsburg		Germany	D-86158
41	GASTRO-Studien	Berlin		Germany	10825
42	Charite - Universitatsmedizin Berlin (CCM)	Berlin		Germany	12203
43	Medizinisches Versorgungszentrum (MVZ) Dachau	Dachau		Germany	85221
44	University Hospital Dresden	Dresden		Germany	1307
45	Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus	Frankfurt		Germany	60431
46	Universitätsklinikum Frankfurt/ Medizinische Klinik 1	Frankfurt		Germany	60590
47	Universitatsklinikum Freiburg	Freiburg		Germany	79106
48	Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH	Halle		Germany	06120
49	Hamburgisches Forschungsinstitut fuer CED, HaFCED e.K.	Hamburg		Germany	20251
50	Gastroenterologie Opernstraße	Kassel		Germany	34117
51	Universitatsklinikum Schleswig-Holstein - Kiel	Kiel		Germany	24105
52	Städtisches Klinikum Lüneburg	Lueneburg		Germany	21339
53	Universitätsklinikum Otto-von-Guericke-Universität Magdeburg	Magdeburg		Germany	39120
54	Medizinische Fakultät Mannheim der Universität Heidelberg	Mannheim		Germany	68167
55	Gastroenterologische Gemeinschaftspraxis Minden	Minden		Germany	32423
56	Klinikum der Universität München	München		Germany	81377
57	Praxis Dr. med. Ulf Helwig	Oldenburg		Germany	26123
58	Zentrum für Gastroenterologie Saar MVZ GmbH	Saarbrücken		Germany	66111
59	Universitaetsklinik Tuebingen	Tübingen		Germany	72076
60	Universitätsklinikum Ulm, Klinik für Innere Medizin II	Ulm		Germany	89081
61	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano		Italy	20122
62	Ospedale Villa Sofia-Cervello	Palermo		Italy	90146
63	Azienda Ospedaliera G.Salvini Ospedale di Rho	RHO		Italy
64	Fondazione Policlinico Gemelli Università Cattolica	Roma		Italy	168
65	Istituto Clinico Humanitas	Rozzano		Italy	20089
66	AO Ordine Mauriziano	Torino		Italy	10128
67	Inje University Haeundae Paik Hospital	Busan		Korea, Republic of	48108
68	Seoul National University Hospital	Seoul		Korea, Republic of	03080
69	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
70	Asan Medical Center	Seoul		Korea, Republic of	05505
71	KyungHee University Hospital	Seoul		Korea, Republic of	102-1703
72	Onze Lieve Vrouwe Gasthuis	Amsterdam		Netherlands	1091 AC
73	Leiden University Medical Center	Leiden		Netherlands	2333 ZA
74	Maastricht Universitair Medisch Centrum	Maastricht		Netherlands	6229 HX
75	Radboudumc	Nijmegen		Netherlands	6525 GA
76	Erasmus MC	Rotterdam		Netherlands	3015 GD
77	Sint Franciscus Gasthuis	Rotterdam		Netherlands	3045 PM
78	Irkutsk State Medical Academy of Postgraduate Education	Irkutsk		Russian Federation	664079
79	Olla-Med, Llc	Moscow		Russian Federation	105554
80	City Clinical Hospital #31	St. Petersburg		Russian Federation	197110
81	GBUZ Respublican Clinical Hospital n.a. GG Kuvatova	Ufa		Russian Federation	450005
82	Hosp. Univ. Fundacion Alcorcon	Alcorcón		Spain	28922
83	Hosp. Arquitecto Marcide	Ferrol		Spain	15405
84	Hosp. Gral. Univ. Gregorio Marañon	Madrid		Spain	28007
85	Hosp. Univ. La Paz	Madrid		Spain	28046
86	Hosp. Univ. Virgen de La Arrixaca	Murcia		Spain	30120
87	Hosp. Virgen de La Victoria	Málaga		Spain	29010
88	Hosp. de Navarra	Pamplona		Spain	31008
89	Hosp. Montecelo	Pontevedra		Spain	36071
90	Corporacio Sanitari Parc Tauli	Sabadell		Spain	08208
91	Hosp. Clinico Univ. de Salamanca	Salamanca		Spain	37007
92	Hosp. Univ. Marques de Valdecilla	Santander		Spain	39008
93	Hosp. Clinico Univ. de Valencia	Valencia		Spain	46010
94	Hosp. Alvaro Cunqueiro	Vigo		Spain	36213
95	Hosp. Clinico Univ. Lozano Blesa	Zaragoza		Spain	50009
96	Hosp. Univ. Miguel Servet	Zaragoza		Spain	50009
97	Gastromottagningen	Malmö		Sweden	20502
98	Gastromottagningen	Stockholm		Sweden	18288
99	Pennine Acute Hospitals-Fairfield General Hospital	Bury		United Kingdom	BL9 7TD
100	Gloucestershire Hospitals NHS Foundation Trust - Cheltenham	Cheltenham		United Kingdom	GL53 7AN
101	Royal Devon & Exeter Hospital	Exeter		United Kingdom	EX2 5DW
102	King's College Hospital NHS Foundation Trust	London		United Kingdom	SE5 9RS
103	St George's Hospital	London		United Kingdom	SW17 OQT
104	Southampton University Hospitals NHS Trust	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

Janssen-Cilag Ltd.

Investigators

Study Director: Janssen-Cilag Ltd. Clinical Trial, Janssen-Cilag Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Janssen-Cilag Ltd.

ClinicalTrials.gov Identifier:

NCT03782376

Other Study ID Numbers:

CR108533
2018-002629-51
CNTO1275CRD3008

First Posted:

Dec 20, 2018

Last Update Posted:

Aug 18, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Crohn Disease

Ustekinumab

Study Results

No Results Posted as of Aug 18, 2022