Clinical trial NCT01235689: Efficacy and Safety of Two Treatment Algorithms in Adults With Moderate to Severe Crohn's Disease
Official title: An Open-Label, Multicenter, Efficacy and Safety Study to Evaluate Two Treatment Algorithms in Subjects With Moderate to Severe Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2010-11-05
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to demonstrate that tight control of disease activity, using stringent criteria based on Crohn's disease activity Index (CDAI), biomarkers (high sensitivity C-reactive protein \[hs-CRP\] and fecal calprotectin), and corticosteroid use, improves the rate of mucosal healing 48 weeks after randomization compared with management using less stringent criteria based only on CDAI and corticosteroid use.

Detailed description: The study included a 1- to 3-week screening period, up to 8 weeks of prednisone run-in treatment, a 48-week post-randomization treatment period, and a 70 day follow-up phone call or clinic visit, for a total duration of up to 69 weeks.

Participants who met entry criteria were enrolled and initiated an oral prednisone regimen at Baseline (Week 0). At the first key visit, participants were randomized into 1 of 2 groups (Tight Control group or Clinically Driven group), with stratification according to screening smoking status, weight, and disease duration.

The first key visit was the randomization visit; subsequent key visits occurred every 12 weeks following the first key visit. Randomization normally took place 9 weeks after Baseline. However, participants who fulfilled the early randomization criteria may have been randomized as early as the Baseline (Week 0) visit. Therapeutic option changes, if appropriate, occurred at key visits based on results from previous success criteria visits.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of ileal, colonic (including rectal), or ileocolonic Crohn's disease (CD) confirmed using imaging technology or endoscopy not more than 6 years prior to Baseline.
* CDAI score of greater than or equal to 220 and less than or equal to 450 at the Baseline visit in participants not receiving prednisone or equivalent at Baseline. CDAI score of greater than or equal to 200 and less than or equal to 450 at the Baseline visit if the participant is receiving prednisone less than or equal to 20 mg or equivalent for at least 7 days before Baseline. CDAI score of greater than 150 and less than or equal to 450 at the Baseline visit if the participant is receiving prednisone higher than 20 mg or equivalent for greater than or equal to 7 days before Baseline
* Participant or his/her legal representative have voluntarily signed and dated an informed consent approved by and compliant with the requirements of this study protocol which has been approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
* Adequate cardiac, renal and hepatic function as determined by the Principal Investigator and demonstrated by Screening laboratory evaluations, questionnaires and physical examination results that do not indicate an abnormal clinical condition which would place the participant at undue risk and thus preclude participation in the study.
* Participant must be able to self-inject and orally administer study medication or have a designee or Healthcare Professional who can assist

Exclusion Criteria:

* Previous or current biologic use for Crohn's disease or participation in a biologic study
* Previous or current use of immunomodulators (e.g., methotrexate, azathioprine, 6-mercaptopurine, JAK inhibitor, alpha-integrin) for Crohn's disease or participation in a Crohn's disease study with immunomodulator(s). Current use of immunomodulators for non-Crohn's disease at Baseline.
* Greater than two previous courses of corticosteroid (systemic corticosteroid) or budesonide) for Crohn's Disease. A course is defined as 1) total duration for burst and taper ≥ 4 weeks and 2) prednisone or equivalent ≥ 40 mg (or budesonide ≥ 9 mg) for at least 2 weeks.
* Participants with a poorly controlled medical condition such as: uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, moderate to severe congestive heart failure (New York Heart Association \[NYHA\] class III or IV), recent cerebrovascular accident and any other condition which, in the opinion of the Investigator or the sponsor, would put the participant at risk by participation in the protocol
* Participants with positive C. difficile stool assay at Screening.

Primary outcomes:
measure: Percentage of Participants With Mucosal Healing and No Deep Ulcerations
timeFrame: 48 weeks after Randomization
Secondary outcomes:
measure: Percentage of Participants in Deep Remission 48 Weeks After Randomization
timeFrame: 48 weeks after Randomization
measure: Percentage of Participants in Biologic Remission 48 Weeks After Randomization
timeFrame: 48 weeks after Randomization
measure: Percentage of Participants With Mucosal Healing 48 Weeks After Randomization
timeFrame: 48 weeks after Randomization
measure: Percentage of Participants With Mucosal Healing and CDEIS < 4 in Every Segment 48 Weeks After Randomization
timeFrame: 48 weeks after Randomization
measure: Percentage of Participants With Complete Mucosal Healing 48 Weeks After Randomization
timeFrame: 48 weeks after Randomization
measure: Percentage of Participants With Endoscopic Response 48 Weeks After Randomization
timeFrame: 48 weeks after Randomization
measure: Change From Baseline in CDEIS at 48 Weeks After Randomization
timeFrame: Baseline and 48 weeks after Randomization
measure: Change From Baseline in CDAI Over Time
timeFrame: Baseline and 4 and 8 weeks during the prednisone run-in, and 2, 6, 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization.
measure: Time to Crohn's Disease Flare
timeFrame: From Randomization to 48 weeks after Randomization
measure: Time to Clinical Remission
timeFrame: From Randomization through 48 weeks after Randomization
measure: Time to Steroid-free Remission
timeFrame: From Randomization through 48 weeks after Randomization
measure: Percentage of Participants in Clinical Remission Over Time
timeFrame: Baseline and 4 and 8 weeks during the prednisone run-in, and 2, 6, 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization.
measure: Percentage of Participants in Steroid-free Remission Over Time
timeFrame: 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization.
measure: Time to All-cause Hospitalization
timeFrame: From Randomization through 48 weeks after Randomization
measure: Time to Crohn's Disease-related Hospitalization or Hospitalization Due to Adverse Event Relating to Study Medication
timeFrame: From Randomization through 48 weeks after Randomization
measure: Number of Major Crohn's Disease-related Surgeries After Randomization
timeFrame: From Randomization through 48 weeks after Randomization
measure: Number of Crohn's Disease-related Hospitalizations After Randomization
timeFrame: From Randomization through 48 weeks after Randomization
measure: Number of All-cause Hospitalizations After Randomization
timeFrame: From Randomization through 48 weeks after Randomization
measure: Total Length of Stay in Hospital for All-cause Hospitalizations
timeFrame: From Randomization through 48 weeks after Randomization
measure: Total Length of Stay in Hospital for Crohn's Disease-related Hospitalizations
timeFrame: From Randomization through 48 weeks after Randomization
measure: Number of Crohn's Disease-related Surgical Procedures After Randomization
timeFrame: From Randomization through 48 weeks after Randomization
measure: Time to Crohn's Disease-related Hospitalization Due to Emergency
timeFrame: From Randomization through 48 weeks after Randomization
measure: Number of Crohn's Disease-related Hospitalizations Due to Emergency
timeFrame: From Randomization through 48 weeks after Randomization
measure: Change in Crohn's Disease Behavior According to Montreal Classification
timeFrame: From Baseline to 48 weeks after Randomization
measure: Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Over Time
timeFrame: Baseline and 8 weeks during the prednisone run-in, and 11, 23, 35, and 48 weeks after Randomization.
measure: Change in Fecal Calprotectin From Baseline to 48 Weeks After Randomization
timeFrame: Baseline and 48 weeks after Randomization
measure: Total Dose of Prednisone
timeFrame: From Baseline through 48 weeks after Randomization
measure: Change From Baseline in Quality of Life in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score
timeFrame: Baseline and 48 weeks after Randomization
measure: Change From Baseline in Work Productivity Activity Index - Crohn's Disease (WPAI:CD)
timeFrame: Baseline and 48 weeks after Randomization
measure: Change From Baseline in Patient Health Questionnaire - 9 (PHQ9)
timeFrame: Baseline and 48 weeks after Randomization
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score
timeFrame: Baseline and 48 weeks after Randomization
measure: Change From Baseline in Short-Form 36 (SF-36) Physical Component Summary and Mental Component Summary Scores
timeFrame: Baseline and 48 weeks after Randomization
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: Anne Robinson, Pharm.D.
role: STUDY_DIRECTOR
References:
citation: Lakatos PL, Kaplan GG, Bressler B, Khanna R, Targownik L, Jones J, Rahal Y, McHugh K, Panaccione R. Cost-Effectiveness of Tight Control for Crohn's Disease With Adalimumab-Based Treatment: Economic Evaluation of the CALM Trial From a Canadian Perspective. J Can Assoc Gastroenterol. 2022 Mar 10;5(4):169-176. doi: 10.1093/jcag/gwac001. eCollection 2022 Aug.
citation: Ungaro RC, Yzet C, Bossuyt P, Baert FJ, Vanasek T, D'Haens GR, Joustra VW, Panaccione R, Novacek G, Reinisch W, Armuzzi A, Golovchenko O, Prymak O, Goldis A, Travis SP, Hebuterne X, Ferrante M, Rogler G, Fumery M, Danese S, Rydzewska G, Pariente B, Hertervig E, Stanciu C, Serrero M, Diculescu M, Peyrin-Biroulet L, Laharie D, Wright JP, Gomollon F, Gubonina I, Schreiber S, Motoya S, Hellstrom PM, Halfvarson J, Butler JW, Petersson J, Petralia F, Colombel JF. Deep Remission at 1 Year Prevents Progression of Early Crohn's Disease. Gastroenterology. 2020 Jul;159(1):139-147. doi: 10.1053/j.gastro.2020.03.039. Epub 2020 Mar 26.
citation: Panaccione R, Colombel JF, Travis SPL, Bossuyt P, Baert F, Vanasek T, Danalioglu A, Novacek G, Armuzzi A, Reinisch W, Johnson S, Buessing M, Neimark E, Petersson J, Lee WJ, D'Haens GR. Tight control for Crohn's disease with adalimumab-based treatment is cost-effective: an economic assessment of the CALM trial. Gut. 2020 Apr;69(4):658-664. doi: 10.1136/gutjnl-2019-318256. Epub 2019 Jul 8.
citation: Colombel JF, Panaccione R, Bossuyt P, Lukas M, Baert F, Vanasek T, Danalioglu A, Novacek G, Armuzzi A, Hebuterne X, Travis S, Danese S, Reinisch W, Sandborn WJ, Rutgeerts P, Hommes D, Schreiber S, Neimark E, Huang B, Zhou Q, Mendez P, Petersson J, Wallace K, Robinson AM, Thakkar RB, D'Haens G. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet. 2017 Dec 23;390(10114):2779-2789. doi: 10.1016/S0140-6736(17)32641-7. Epub 2017 Oct 31.