Efficacy and Long Term Safety of Adalimumab in Pediatric Subjects Who Have Demonstrated Clinical Response in M06-806

NCT00686374 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: M06-8072007-006494-90
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was a multicenter, open-label study to evaluate the human monoclonal anti-TNF-α antibody adalimumab as an effective therapy for maintaining clinical response in pediatric participants with Crohn's disease (CD) and to gather long-term safety and tolerability data in this population. Participants were allowed to enroll in the study if they participated in and successfully completed Study M06-806 (NCT00409682) through Week 52.

Conditions

Crohn's Disease

Keywords

Crohn's Disease; adalimumab

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Achieved Pediatric Crohn's Disease Activity Index (PCDAI) Clinical Remission Over Time

  Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical remission was defined as PCDAI ≤ 10.

  Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408

• Number of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score Over Time

  Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. The baseline PCDAI value was defined as the last non-missing value on or before the date of the first dose of study drug during Study M06-806. Clinical response was defined as a PCDAI ≥ 15 points lower than the Study M06-806 baseline PCDAI value.

  Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408

Secondary Outcomes (6)

• Number of Participants Who Were in Crohn's Disease Activity Index (CDAI) Clinical Remission Over Time

  Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408

• Number of Participants Who Were in Crohn's Disease Activity Index (CDAI) Clinical Response Over Time

  Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408

• Number of Participants in Steroid-free Pediatric Crohn's Disease Activity Index (PCDAI) Remission Over Time

  Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384

• Number of Participants in Steroid-free Crohn's Disease Activity Index (CDAI) Remission Over Time

  Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384

• Mean Change From Baseline in Pediatric Crohn's Disease Activity Index (PCDAI) Over Time

  Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384

Study Arms (1)

Any adalimumab

EXPERIMENTAL

Adalimumab was administered via subcutaneous injection. Dosage was based on body weight and clinical status, and ranged from 10, 20, or 40 mg every other week to 20 or 40 mg every week.

Biological: Adalimumab

Interventions

Adalimumab BIOLOGICAL

Participants who enrolled into the study from blinded therapy in Study M06-806 received open-label (OL) therapy at a dose dependent on their body weight. Participants weighing ≥ 40 kg received 40 mg of adalimumab every other week (eow), and those who weighed \< 40 kg received 20 mg of adalimumab eow. Starting at Week 8, participants who had a disease flare may have been switched to every week (ew) treatment at the same dose of adalimumab received while on eow treatment. Participants who enrolled from OL therapy in Study M06-806 continued to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the Week 52 visit of Study M06-806. Adalimumab dose could have been decreased to the next lower treatment level for those with body weight changes. Participants who responded to treatment may have also had their dosage frequency decreased from ew to eow dosing, as well as a decrease in dosage.

Also known as: ABT-D2E7, Humira

Any adalimumab

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant must have successfully enrolled in and completed Study M06-806 through Week 52.
• Participant must have been a responder at any time point during the M06-806 study (defined as having achieved at least a 15-point reduction in the Pediatric Crohn's Disease Activity Index (PCDAI) from Baseline).
• If female, participants who were sexually active and of child-bearing potential were to be practicing an approved method of birth control throughout the study and for 150 days after study drug administration. Examples of approved methods of birth control included the following:
• Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD)
• Oral, parenteral or intravaginal contraceptives
• A vasectomized partner
• Participant of legal age, parent or legal guardian, as required, voluntarily signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form, after the nature of the study was explained and the participant of legal age, participant's parent, or legal guardian, as required, had the opportunity to ask questions. Participants were to be included in all discussions, and if required, their signature on an assent form was to be obtained.
• Parent or legal guardian of participant who was not of legal age, as required, must have been willing to actively supervise storage and administration of study drug and to ensure that the time of each dose was accurately recorded in the participant's diary.
• Participants of legal age, must have been willing to actively store, administer, and accurately record study drug administration in the participant diary.
• Participant was judged to be in acceptable medical condition, as determined by the Principal Investigator based upon results of clinical and laboratory evaluations done throughout the preceding Crohn's disease study M06-806.

You may not qualify if:

• For any reason, the participant was considered by the Investigator to be an unsuitable candidate for continuing therapy in the M06-807 study.
• Participant had abnormal laboratory or other test results that in the opinion of the Investigator would make the participant unsuitable to participate in this study.
• History of cancer or lymphoproliferative disease other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma in-situ of the cervix.
• Participant with known, symptomatic obstructive strictures.
• Participant who was planning surgical bowel resection at any time point while enrolled in the study.
• Participant who had short bowel syndrome as determined by the Investigator.
• Participant who was receiving total parenteral nutrition (TPN).
• Participant who was unwilling to discontinue growth hormone prior to the first dose of open-label study drug at the Baseline visit of M06-807.
• Female participant who was pregnant or currently breastfeeding.
• Participant with a history of clinically significant drug or alcohol abuse in the last year.
• Participant with a poorly controlled medical condition such as: uncontrolled diabetes, recurrent infections, unstable ischemic heart disease, moderate to severe heart failure, recent cerebrovascular accidents or any other condition which, in the opinion of the Investigator or the Sponsor, would put the participant at risk by participation in the protocol.
• Participant with any prior exposure to Tysabri (natalizumab).
• Participant with a known hypersensitivity to the excipients of adalimumab as stated in the label.
• Participant with a previous history of dysplasia of the gastrointestinal tract.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Related Publications (3)

• Faubion WA, Dubinsky M, Ruemmele FM, Escher J, Rosh J, Hyams JS, Eichner S, Li Y, Reilly N, Thakkar RB, Robinson AM, Lazar A. Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease. Inflamm Bowel Dis. 2017 Mar;23(3):453-460. doi: 10.1097/MIB.0000000000001021.

  PMID: 28129288 RESULT

• Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. J Pediatr. 2018 Oct;201:166-175.e3. doi: 10.1016/j.jpeds.2018.05.042. Epub 2018 Jul 25.

  PMID: 30054164 DERIVED

• Ruemmele FM, Rosh J, Faubion WA, Dubinsky MC, Turner D, Lazar A, Eichner S, Maa JF, Alperovich G, Robinson AM, Hyams JS. Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2. J Crohns Colitis. 2018 Nov 9;12(10):1249-1254. doi: 10.1093/ecco-jcc/jjy087.

  PMID: 29939254 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Crohn Disease

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• Andreas Lazar

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2008
• First Posted: May 29, 2008
• Study Start: May 1, 2008
• Primary Completion: April 4, 2017
• Study Completion: April 4, 2017
• Last Updated: July 2, 2018
• Results First Posted: April 20, 2018

Record last verified: 2018-03