Extension Trial Assessing the Safety and Efficacy of BI 655066/ABBV-066/Risankizumab in Patients With Moderate to Severe Chronic Plaque Psoriasis

• ClinicalTrials.gov Identifier: NCT02203851
• Recruitment Status: Completed
• First Posted: July 30, 2014
• Results First Posted: November 8, 2019
• Last Update Posted: November 8, 2019
• Sponsor: AbbVie
• Collaborator: Boehringer Ingelheim
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: July 29, 2014
• First Posted Date: July 30, 2014
• Results First Submitted Date: May 10, 2019
• Results First Posted Date: November 8, 2019
• Last Update Posted Date: November 8, 2019
• Actual Study Start Date: November 20, 2014
• Actual Primary Completion Date: September 4, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 21, 2019)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug in either the lead-in or extension study until 12 weeks after the last dose of study drug (approximately 4 years from the first dose in either the lead-in or extension study) ]
  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event with an onset after the first dose of risankizumab in this study. See the Adverse Event section for details.
• Number of Participants With Drug-related TEAEs [ Time Frame: From first dose of study drug in either the lead-in or extension study until 12 weeks after the last dose of study drug (approximately 4 years from the first dose in either the lead-in or extension study) ]
  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event with an onset after the first dose of risankizumab in this study. See the Adverse Event section for details.
• Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: From first dose of study drug in either the lead-in or extension study until 12 weeks after the last dose of study drug (approximately 4 years from the first dose in either the lead-in or extension study) ]
  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event with an onset after the first dose of risankizumab in this study. See the Adverse Event section for details.
• Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI90) Score at Week 48 in the Extended Dosing Period [ Time Frame: Baseline, Week 48 ]
  Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. Baseline PASI for this study is defined as the baseline PASI in the lead-in study. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100.

Original Primary Outcome Measures (submitted: July 29, 2014)

• Achievement of a greater than or equal to 90% reduction in PASI (Psoriasis Area and Severity Index) score from baseline (i.e., achieving PASI 90) at the week 12 visit. Baseline PASI for this study is defined as the baseline PASI for the 1311.2 study. [ Time Frame: 12 Weeks ]
• Occurrence of Adverse Events (AEs) [ Time Frame: 54 months ]
• Occurrence of Drug-related AEs [ Time Frame: 54 months ]
• Occurrence of Serious Adverse Events (SAEs) [ Time Frame: 54 months ]

Current Secondary Outcome Measures (submitted: October 21, 2019)

• Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 48 of Extended Dosing Period [ Time Frame: Week 48 ]
  The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. Baseline is defined as the last non-missing value on or before the date of the first dose of study drug in the lead-in study.
• Percentage of Participants Achieving 50% Improvement in PASI (PASI50) Score at Week 48 in the Extended Dosing Period [ Time Frame: Baseline, Week 48 ]
  PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI50 is defined as at least a 50% reduction in PASI score compared with the Baseline PASI score. Baseline PASI for this study is defined as the baseline PASI in the lead-in study. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100.
• Percentage of Participants Achieving 75% Improvement in PASI (PASI75) Score at Week 48 in the Extended Dosing Period [ Time Frame: Baseline, Week 48 ]
  PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. Baseline PASI for this study is defined as the baseline PASI in the lead-in study. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100.
• Percentage of Participants Achieving 100% Improvement in PASI (PASI100) Score at Week 48 in the Extended Dosing Period [ Time Frame: Baseline, Week 48 ]
  PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. Baseline PASI for this study is defined as the baseline PASI in the lead-in study. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100.
• Percentage of Participants Achieving sPGA of Clear at Week 48 of Extended Dosing Period [ Time Frame: Week 48 ]
  The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. Baseline is defined as the last non-missing value on or before the date of the first dose of study drug in the lead-in study.

Original Secondary Outcome Measures (submitted: July 29, 2014)

• Achievement of PASI 50 at the week 12 visit [ Time Frame: 54 months ]
• Proportion of patients achieving an Static Physician Global Assessment (sPGA) of clear or almost clear [ Time Frame: 54 months ]
• Achievement of PASI 75 at the week 12 visit [ Time Frame: 54 months ]
• Achievement of PASI 100 at the week 12 visit [ Time Frame: 54 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Extension Trial Assessing the Safety and Efficacy of BI 655066/ABBV-066/Risankizumab in Patients With Moderate to Severe Chronic Plaque Psoriasis
• Official Title: An Open Label Extension Trial Assessing the Safety and Efficacy of BI 655066/ ABBV-066/Risankizumab Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque Psoriasis
• Brief Summary: The primary objective of Study M16-009 was to investigate the safety of risankizumab in participants with moderate to severe chronic plaque psoriasis who were receiving long-term treatment. Additional study objectives were to further investigate the long-term efficacy, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of risankizumab.

Detailed Description

Participants who had successfully completed Study 1311.2 (NCT02054481; the lead-in study) and met the eligibility criteria for Study M16-009 (extension study) had the option to enter the extension study. Participants were allowed to have the End of Study Visit in the lead in study combined with the Week 0 Visit for the extension study. At the Week 12 visit, participants were assigned to treatment based on 90% improvement in Psoriasis Area and Severity Index (PASI90) Score: participants with ≥PASI90 Score at Week 12 continued to receive risankizumab 90 mg by subcutaneous (SC) injection; participants with <PASI90 Score at Week 12 switched to risankizumab 180 mg by SC injection.

Efficacy results are summarized by the 4 treatment groups from the lead-in study, which included the following: Participants who received risankizumab 18 mg in the lead-in study and risankizumab in the extension study (Risankizumab 18 mg/Risankizumab); participants who received risankizumab 90 mg in the lead-in study and risankizumab in the extension study (Risankizumab 90 mg/Risankizumab); participants who received risankizumab 180 mg in the lead-in study and risankizumab in the extension study (Risankizumab 180 mg/Risankizumab); and participants who received ustekinumab (Stelara) 45 or 90 mg in the lead-in study and risankizumab in the extension study (Ustekinumab/Risankizumab).

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Psoriasis

Intervention

Drug: Risankizumab

Risankizumab administered by subcutaneous (SC) injection

Other Names:

• BI 655066
• ABBV-066
• SKYRIZI

Study Arms

• Experimental: Risankizumab 90 mg
  Participants entered the study receiving risankizumab 90 mg by subcutaneous (SC) injection and had achieved ≥90% improvement in Psoriasis Area and Severity Index (PASI90) Score at Week 12 continued to receive open-label (OL) risankizumab 90 mg by SC injection at Week 12 and every 12 weeks for approximately 4 years from the first dose in either the lead-in or extension study.
  Intervention: Drug: Risankizumab
• Experimental: Risankizumab 180 mg
  Participants entered the study receiving risankizumab 90 mg by subcutaneous (SC) injection and had achieved <90% improvement in Psoriasis Area and Severity Index (PASI90) Score at Week 12 switched to open-label (OL) risankizumab 180 mg by SC injection at Week 12 and every 12 weeks for approximately 4 years from the first dose in either the lead-in or extension study.
  Intervention: Drug: Risankizumab

• Publications *: Papp KA, de Vente S, Zeng J, Flack M, Padilla B, Tyring SK. Long-Term Safety and Efficacy of Risankizumab in Patients with Moderate-to-Severe Chronic Plaque Psoriasis: Results from a Phase 2 Open-Label Extension Trial. Dermatol Ther (Heidelb). 2021 Jan 29. doi: 10.1007/s13555-021-00490-3. [Epub ahead of print]

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 5, 2018): 110
• Original Estimated Enrollment (submitted: July 29, 2014): 136
• Actual Study Completion Date: September 4, 2018
• Actual Primary Completion Date: September 4, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

• Participants with moderate to severe chronic plaque psoriasis, who have successfully completed Study 1311.2 (NCT02054481; the lead-in study). Successful completion of the lead-in study is defined as either of the following:

  1. Completion of the entire follow up period, thus reaching End-of-study (EOS) visit.
  2. Loss of response, defined as decrease in response to achieving < 50% improvement in Psoriasis Area and Severity Index Score (PASI50) at any time from Week 24.
• Participant must give informed consent and sign an approved consent form prior to any study procedures in accordance with Good Clinical Practice (GCP) and local legislation
• Applicable only for female participants:
• Negative urine pregnancy dip stick test at the roll-over visit, and if available at roll-over visit, negative Serum ß-Human Chorionic Gonadotropin (ß-HCG) test.

In addition:

Women of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopausal), that, if sexually active agree to use one of the appropriate medically accepted methods of birth control in addition to the consistent and correct use of a condom from date of the roll-over visit until 12 weeks after last treatment in this study. Medically accepted methods of contraception are: ethinyl estradiol containing contraceptives, diaphragm with spermicide substance, and intra-uterine-device.

OR

Female participants which have vasectomized sexual partner(s) (vasectomy at least 1 year prior to enrollment).

OR

Surgically sterilized female participants with documentation of prior hysterectomy, tubal ligation or complete bilateral oophorectomy.

OR

Postmenopausal women with postmenopausal is defined as permanent cessation ≥ 1 year of previously occurring menses.

Exclusion criteria:

• Participants who experienced any drug related serious adverse event (SAE) in the lead-in study
• Participants who have developed guttate, erythrodermic or pustular psoriasis or drug-induced psoriasis (as diagnosed by the investigator), during the lead-in study.
• Evidence of current or previous clinically significant disease, medical condition other than psoriasis, or finding of the medical examination (including vital signs and electrocardiography [ECG]), that in the opinion of the investigator, would compromise the safety of the participant or the quality of the data.
• Known clinically important acute or chronic infections including hepatitis, human immunodeficiency virus (HIV). In regards to tuberculosis (TB), the following applies:
• Signs or symptoms suggestive of current active or latent TB upon medical history, physical examination and/or a chest radiograph (both posterior-anterior and lateral views, taken within 3 months prior to the first administration of study drug and read by a qualified radiologist).
• History of latent or active TB prior to screening, except for participants with documented completion of an adequate treatment regimen, at least 6 months prior to the first administration of study agent.
• Positive QuantiFERON-TB Gold In-Tube test (IGRA) within 2 months prior to the roll-over visit (if available), in which active TB has not been ruled out. This does not apply to participants with history of latent TB with documented completion of an adequate treatment regimen, at least 6 months prior to the first administration of study agent.
• Participants who have developed malignancy, or suspicion of active malignant disease during the lead-in study (except treated cutaneous squamous cell or basal cell carcinoma or carcinoma in situ of the cervix that have been adequately treated).
• Intake of restricted medications or other drugs considered likely to interfere with the safe conduct of this study, as assessed by the investigator.
• Alcohol or drug abuse within 3 months prior to the roll-over visit that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures in the opinion of the investigator.
• Any clinically significant laboratory abnormalities based on the last available laboratory results received during the lead-in study (according to the investigator's medical assessment).
• Pre-menopausal woman who is pregnant or nursing.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Canada, France, Germany, United States

Administrative Information

• NCT Number: NCT02203851
• Other Study ID Numbers: M16-009; 2014-001687-36 ( EudraCT Number ); 1311.13 ( Other Identifier: Boehringer Ingelheim )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Responsible Party: AbbVie
• Study Sponsor: AbbVie
• Collaborators: Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: AbbVie
• Verification Date: October 2019