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

Ankylosing Spondylitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03215277
• Other study ID #: AS0013
• Secondary ID: 2017-000957-37
• Status: Completed
• Phase: Phase 2
• Start date: October 4, 2017
• Est. completion date: May 25, 2020

Study information

• Verified date: July 2023
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: May 25, 2020
• Est. primary completion date: May 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (TNFa) 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-TNFa agent. Subjects may not have been on more than 1 anti-TNFa 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 TNFa 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 TNFa 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

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylarthritis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Drug:
• Bimekizumab
One bimekizumab dose will be administered.
• Certolizumab pegol
Two certolizumab pegol doses will be administered. One of these doses is a loading dose.

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

Locations

Country	Name	City	State
Czechia	As0013 202	Kladno
Czechia	As0013 205	Ostrava
Czechia	As0013 201	Praha 2
Czechia	As0013 203	Praha 3
Germany	As0013 302	Berlin
Germany	As0013 306	Berlin
Germany	As0013 304	Erlangen
Germany	As0013 303	Hamburg
Germany	As0013 301	Herne
Greece	As0013 405	Athens
Greece	As0013 404	Heraklion
Greece	As0013 401	Patra
Greece	As0013 402	Thessaloníki
Greece	As0013 406	Thessaloníki
Moldova, Republic of	As0013 501	Chisinau
Netherlands	As0013 601	Amsterdam
Poland	As0013 708	Bialystok
Poland	As0013 709	Kraków
Poland	As0013 706	Olsztyn
Poland	As0013 703	Poznan
Poland	As0013 702	Torun
Poland	As0013 701	Warsaw
Poland	As0013 704	Warszawa
Poland	As0013 707	Wroclaw
Russian Federation	As0013 801	Kazan
Russian Federation	As0013 803	Kemerovo
Russian Federation	As0013 806	Moscow
Russian Federation	As0013 807	Moscow
Russian Federation	As0013 802	Yaroslavl
Russian Federation	As0013 805	Yaroslavl
United States	As0013 903	Lincoln	Nebraska
United States	As0013 906	Memphis	Tennessee
United States	As0013 902	Oklahoma City	Oklahoma
United States	As0013 908	Ormond Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Greece,  Moldova, Republic of,  Netherlands,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12	ASDAS was calculated as the sum of the results from the following components: 0.121xTotal spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result), 0.058xDuration of morning stiffness (BASDAI Question 6 result), 0.110xPGADA, 0.073xPeripheral pain/swelling (BASDAI Question 3 result), 0.579x(natural logarithm of the CRP [mg/L] + 1), Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.980 for ASDAS (as a fixed value of 2 was assumed for values of hs-CRP below the LLOQ), but no defined upper score. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. Posterior means and 95% credible intervals in each group are presented.	From Baseline to Week 12
Primary	Number of Participants With Adverse Events (AE) During the Study Conduct	An AE was any untoward medical occurrence in a patient or clinical investigation participant 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. A treatment-emergent adverse event (TEAE) was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP.	From Baseline until Safety Follow-Up Visit (up to Week 64)
Primary	Number of Participants With Serious Adverse Events (SAEs) During the Study Conduct	An SAE was any untoward medical occurrence that at any dose: - Resulted in death - Is life-threatening - Required 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 jeopardised the participants, or may require medical or surgical intervention to prevent any of the above. A TEAE was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP.	From Baseline until Safety Follow-Up Visit (up to Week 64)
Primary	Number of Participants Who Withdrew Due to an Adverse Event (AE) During the Study Conduct	An AE was any untoward medical occurrence in a patient or clinical investigation participant 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. A TEAE was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP.	From Baseline until Safety Follow-Up Visit (up to Week 64)
Secondary	Number of Participants With Ankylosing Spondylitis Disease Activity Score - Inactive Disease (ASDAS-ID) at Week 12	ASDAS-ID was defined by ASDAS < 1.3. ASDAS was calculated as the sum of the results from the following components: 0.121xTotal spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result), 0.058xDuration of morning stiffness (BASDAI Question 6 result), 0.110xPGADA, 0.073xPeripheral pain/swelling (BASDAI Question 3 result), 0.579x(natural logarithm of the CRP [mg/L] + 1), Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.980 for ASDAS (as a fixed value of 2 was assumed for values of hs-CRP below the LLOQ), but no defined upper score.	Week 12
Secondary	Number of Participants With Ankylosing Spondylitis Disease Activity Score-Major Improvement (ASDAS-MI) at Week 12	ASDAS-MI was defined by a reduction (improvement) from Baseline in ASDAS >=2 units. ASDAS was calculated as the sum of the results from the following components: 0.121xTotal spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result), 0.058xDuration of morning stiffness (BASDAI Question 6 result), 0.110xPGADA, 0.073xPeripheral pain/swelling (BASDAI Question 3 result), 0.579x(natural logarithm of the CRP [mg/L] + 1), Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.980 for ASDAS (as a fixed value of 2 was assumed for values of hs-CRP below the LLOQ), but no defined upper score.	Baseline, Week 12

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