A Study to Test the Efficacy and Safety of Bimekizumab and Certolizumab Pegol in Patients With Active Ankylosing Spondylitis

• ClinicalTrials.gov Identifier: NCT03215277
• Recruitment Status: Completed
• First Posted: July 12, 2017
• Last Update Posted: May 25, 2021
• Sponsor: UCB Biopharma S.P.R.L.
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma S.P.R.L. )

Tracking Information

• First Submitted Date: July 5, 2017
• First Posted Date: July 12, 2017
• Last Update Posted Date: May 25, 2021
• Actual Study Start Date: October 4, 2017
• Actual Primary Completion Date: May 25, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 14, 2019)

• Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12 [ Time Frame: From Baseline to Week 12 ]
  ASDAS is calculated as the sum of the following components:

  • 0.121 x Total spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result)
  • 0.058 x Duration of morning stiffness (BASDAI Question 6 result)
  • 0.110 x Patient's Global Assessment of Disease Activity (PGADA)
  • 0.073 x Peripheral pain/swelling (BASDAI Question 3 result)
  • 0.579 x (natural logarithm of the C-reactive protein (CRP) [mg/L] + 1)

  Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling are all assessed on a numerical scale (0 to 10 units). The results of each of these component calculations are summed to obtain the ASDAS.
• Incidence of adverse events (AE) during the study conduct [ Time Frame: From Screening until Safety Follow-Up Visit (up to Week 64) ]
  An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
• Incidence of serious adverse events (SAEs) during the study conduct [ Time Frame: From Screening until Safety Follow-Up Visit (up to Week 64) ]
  An SAE is any untoward medical occurrence that at any dose:

  • Results in death
  • Is life-threatening
  • Requires in patient hospitalisation or prolongation of existing hospitalisation
  • Is a congenital anomaly or birth defect
  • Is an infection that requires treatment with parenteral antibiotics
  • Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above
• Number of subjects who withdrew due to an adverse event (AE) during the study conduct [ Time Frame: From Screening until Safety Follow-Up Visit (up to Week 64) ]
  An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Original Primary Outcome Measures (submitted: July 11, 2017)

• Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12 [ Time Frame: From Baseline to Week 12 ]
  The ASDAS score is calculated as the sum of the following components: 0.121 × Back pain (BASDAI Question (Q)2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × PtGADA, 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm of the CRP [mg/L] + 1) Spinal pain, PtGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units). The results of these calculations are summed to calculate the ASDAS.
• Incidence of Adverse Events (AE) during the study conduct [ Time Frame: From Screening until Safety Follow-Up Visit (up to Week 64) ]
  An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
• Incidence of Serious Adverse Events (SAEs) during the study conduct [ Time Frame: From Screening until Safety Follow-Up Visit (up to Week 64) ]
  An SAE is any untoward medical occurrence that at any dose:

  • Results in death
  • Is life-threatening
  • Requires in patient hospitalisation or prolongation of existing hospitalisation
  • Is a congenital anomaly or birth defect
  • Is as infection that requires treatment with parenteral antibiotics
  • Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above
• Number of subjects who withdrew due to an Adverse Event (AE) during the study conduct [ Time Frame: From Screening until Safety Follow-Up Visit (up to Week 64) ]
  An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Current Secondary Outcome Measures (submitted: October 14, 2019)

• Percentage of subjects with Ankylosing Spondylitis Disease Activity Score - Inactive Disease (ASDAS-ID) at Week 12 [ Time Frame: Week 12 ]
  ASDAS-ID is defined by ASDAS < 1.3. ASDAS is calculated as the sum of the following components:

  • 0.121 x Total spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result)
  • 0.058 x Duration of morning stiffness (BASDAI Question 6 result)
  • 0.110 x Patient's Global Assessment of Disease Activity (PGADA)
  • 0.073 x Peripheral pain/swelling (BASDAI Question 3 result)
  • 0.579 x (natural logarithm of the C-reactive protein (CRP) [mg/L] + 1)

  Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling are all assessed on a numerical scale (0 to 10 units). The results of each of these component calculations are summed to obtain the ASDAS.
• Percentage of subjects with Ankylosing Spondylitis Disease Activity Score-Major Improvement (ASDAS-MI) at Week 12 [ Time Frame: Baseline, Week 12 ]
  ASDAS-MI is defined by a reduction (improvement) from Baseline in ASDAS >=2 units. ASDAS is calculated as the sum of the following components:

  • 0.121 x Total spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result)
  • 0.058 x Duration of morning stiffness (BASDAI Question 6 result)
  • 0.110 x Patient's Global Assessment of Disease Activity (PGADA)
  • 0.073 x Peripheral pain/swelling (BASDAI Question 3 result)
  • 0.579 x (natural logarithm of the C-reactive protein (CRP) [mg/L] + 1)

  Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling are all assessed on a numerical scale (0 to 10 units). The results of each of these component calculations are summed to obtain the ASDAS.

Original Secondary Outcome Measures (submitted: July 11, 2017)

• Percentage of subjects meeting the Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID) response criteria at Week 12 [ Time Frame: Week 12 ]
  The ASDAS-Inactive Disease score is defined as: ASDAS < 1.3. The ASDAS score is calculated as the sum of the following components: 0.121 × Back pain (BASDAI Question (Q)2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × PtGADA, 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm of the CRP [mg/L] + 1) Spinal pain, PtGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units). The results of these calculations are summed to calculate the ASDAS.
• Percentage of subjects meeting the Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) response criteria at Week 12 [ Time Frame: Week 12 ]
  ASDAS-MI is achieved when there is a reduction (improvement) >= 2.0 in the ASDAS relative to Baseline. The ASDAS is calculated as the sum of the following components: 0.121 × Back pain (BASDAI Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × PtGADA 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm of the CRP [mg/L] + 1) Back pain, PtGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units). The results of these calculations are summed to calculate the ASDAS.
• Osteoblastic activity as detected by imaging techniques at Week 12 [ Time Frame: Week 12 ]
  The 18F-fluoride positron-emission tomography - magnetic resonance imaging (PET-MRIs) of the whole spine will be performed by using a whole-body PET/MRI system. Alternatively, subjects will be examined in supine position on a combined PET-computerized tomography (CT) system permitting the acquisition of co-registered CT and PET images in the same session. The PET-MRI or PET-CT scan will be performed at time points provided in approximately 25 subjects at selected sites.
• Osteoblastic activity as detected by imaging techniques at Week 48 [ Time Frame: Week 48 ]
  The 18F-fluoride positron-emission tomography - magnetic resonance imaging (PET-MRIs) of the whole spine will be performed by using a whole-body PET/MRI system. Alternatively, subjects will be examined in supine position on a combined PET-computerized tomography (CT) system permitting the acquisition of co-registered CT and PET images in the same session. The PET-MRI or PET-CT scan will be performed at time points provided in approximately 25 subjects at selected sites.

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

Descriptive Information

• Brief Title: A Study to Test the Efficacy and Safety of Bimekizumab and Certolizumab Pegol in Patients With Active Ankylosing Spondylitis
• Official Title: A Multicenter, Phase 2A, Randomized, Investigator-Blind, Subject-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of Bimekizumab and Certolizumab Pegol in Subjects With Active Ankylosing Spondylitis
• Brief Summary: The purpose of the study is to evaluate the efficacy and safety of bimekizumab compared to certolizumab pegol in the treatment of subjects with active ankylosing spondylitis (AS).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

This is an investigator-blind and subject-blind study.

Primary Purpose: Treatment

• Condition: Ankylosing Spondylitis

Intervention

• Drug: Bimekizumab
  One bimekizumab dose will be administered.
  Other Names:

  • UCB4940
  • BKZ
• Drug: Certolizumab pegol
  Two certolizumab pegol doses will be administered. One of these doses is a loading dose.
  Other Names:

  • CZP
  • Cimzia
  • CDP870
• Other: Placebo
  Placebo will be provided to maintain the blinding.

Study Arms

• Experimental: Bimekizumab
  Subjects will receive several bimekizumab administrations on pre-defined time points. Placebo will be provided in this arm to mask the certolizumab pegol loading dose.
  Interventions:

  • Drug: Bimekizumab
  • Other: Placebo
• Experimental: Certolizumab pegol
  Subjects will receive several certolizumab pegol administrations on pre-defined time points.
  Intervention: Drug: Certolizumab pegol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 6, 2019): 76
• Original Estimated Enrollment (submitted: July 11, 2017): 60
• Actual Study Completion Date: May 25, 2020
• Actual Primary Completion Date: May 25, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Documented diagnosis of active adult-onset ankylosing spondylitis (AS) as defined by documented radiologic evidence (X-ray) fulfilling the Modified New York criteria for AS (1984) of at least 3 months' symptom duration and age of onset <45 years

• Subject has moderate to severe active disease at the Screening Visit as defined by each of the following:

  1. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >=4
  2. Spinal pain >=4 on a 0 to 10 numeric rating scale (NRS) (from BASDAI Item 2)
• Subjects must have had an inadequate response to, have a contraindication to, or have been intolerant to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs)
• Subjects taking corticosteroids must be on a maximum daily dose of <=10mg/day oral prednisolone or equivalent
• Subjects taking methotrexate (MTX; <=25 mg/week) are allowed to continue their medication if they received a stable dose for at least 12 weeks before randomization
• Subjects taking sulfasalazine (up to 3 grams/day) or hydroxychloroquine (up to 400 mg per day total) are allowed to continue their medication if started at least 12 weeks prior to randomization
• Subject who has been on an anti-tumor necrosis factor alpha (TNFα) agent must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months or have been intolerant to at least 1 administration of an anti-TNFα agent. Subjects may not have been on more than 1 anti-TNFα agent
• Subject has high-sensitive C-Reactive Protein (hsCRP) levels >=3 mg/L at the Screening Visit
• Female subjects must be postmenopausal, permanently sterilized or, if of childbearing potential, must be willing to use a highly effective method of contraception up till 20 weeks after last administration of investigational medicinal product (IMP)
• Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active, up till 20 weeks after the last administration of IMP

Exclusion Criteria:

• Subject has received previous or current biological treatment other than TNFα inhibitor treatment
• Subjects with a total ankylosis of the spine, or a diagnosis of any other inflammatory arthritis eg, rheumatoid arthritis (RA), sarcoidosis, systemic lupus erythematosus, or reactive arthritis
• Subjects with any current sign or symptom that may indicate an active infection (except for the common cold)
• Subject has received previous or current biological treatment other than TNFα inhibitor treatment
• Subject has chronic, recurrent, recent serious / life-threatening or current infection, as defined in the protocol
• Subject has history of certain atypical infections, viral hepatitides, human immunodeficiency virus (HIV) infection, tuberculosis, as defined in the protocol
• Subjects receiving any live vaccination within the 8 weeks prior to Baseline
• Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, with latent TB infection or current or history of nontuberculous mycobacteria (NTMB) infection
• Subject has immunosuppressive condition or treatment, recent history of malignancy (some exceptions) or demyelinating disease

• Subjects with concurrent malignancy or a history of malignancy during the past 5 years will be excluded, with following exceptions that may be included:

  1. <= 3 excised or ablated basal cell carcinomas of the skin
  2. One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of recurrence or metastases for more than 2 years prior to Screening
  3. Actinic keratosis (-es)
  4. Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening
• Subject has history of psychiatric disorder, including suicidality (as defined in the protocol
• Subject has major abnormalities on laboratory testing, as defined in the protocol

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: Czechia, Germany, Greece, Moldova, Republic of, Netherlands, Poland, Russian Federation, United States
• Removed Location Countries: Australia

Administrative Information

• NCT Number: NCT03215277
• Other Study ID Numbers: AS0013; 2017-000957-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.clinicalstudydatarequest.com and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if a determination is made that the data cannot be adequately anonymized.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.clinicalstudydatarequest.com and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• URL: http://clinicalstudydatarequest.com

• Current Responsible Party: UCB Pharma ( UCB Biopharma S.P.R.L. )
• Original Responsible Party: Same as current
• Current Study Sponsor: UCB Biopharma S.P.R.L.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; +1-844-599-2273 (UCB)

• PRS Account: UCB Pharma
• Verification Date: May 2021