Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001092987
Ethics application status
Approved
Date submitted
17/08/2020
Date registered
20/10/2020
Date last updated
18/06/2021
Date data sharing statement initially provided
20/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to test different doses of BI 730357 and find out the effect they have on symptoms in people with active psoriatic arthritis
Scientific title
A Phase II, randomised, double-blind, placebo-controlled, parallel-group, dose-ranging, efficacy and safety trial of BI 730357 given for 12 weeks in patients with active psoriatic arthritis
Secondary ID [1] 302042 0
1407-0004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psoriatic Arthritis 318628 0
Condition category
Condition code
Inflammatory and Immune System 316649 316649 0 0
Rheumatoid arthritis
Musculoskeletal 317056 317056 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised, double-blind, placebo-controlled, parallel group, doseranging, of treatment over 12 weeks with three BI 730357 dose levels compared to placebo. 160 patients globally will be randomised in a 1:1:1:1 ratio in the following groups:
Arm 1: 100 mg, n=40
Arm 2: 200 mg, n=40
Arm 3: 400 mg, n=40
The doses listed above will be administered in tablet form. Every patient will be required to take 3 tablets, once per day for 12 weeks. The patient's adherence to taking the trial medication will be checked by clinical trial staff at study visits. The patient will be required to complete a diary to document their compliance.
Arm 4: matching placebo, n=40
Intervention code [1] 318338 0
Treatment: Drugs
Comparator / control treatment
A placebo-control design is required for evaluation of evaluation of BI 730357 efficacy and safety. In addition, a placebo arm is needed in order to avoid potential confounding factors, such as:
-placebo effect,
-potential investigator bias in safety and efficacy assessment or,-regression to the mean in endpoint scoring.

Placebo tablets have been developed that contain mannitol, microcrystalline cellulose, magnesium stearate, and the same film coating (as the verum). The clinical trial supplies are provided in aluminum/aluminum blisters. Patient are permitted to continue taking concomitant medication for their psoriatic arthritis, so as long as this dose has been stable prior to and during the clinical trial.
For patients receiving methotrexate (MTX): patient has received treatment for greater than or equal to 3 months, with stable dose and stable route of administration (not to exceed 20 mg MTX per week) for greater than or equal to 4 weeks prior to randomisation to EOO; patients on MTX should be taking folic acid supplementation according to local standard of care before randomisation and during the trial to minimize the likelihood of MTX associated toxicity
For patients receiving oral corticosteroids: the patient must be on a stable dose (not to exceed the equivalent of 10 mg of prednisone per day) for greater than or equal to 2 weeks prior to randomisation to follow-up visit,
For patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol/acetaminophen as required: the patient must be on stable dose for greater than or equal to 2 weeks prior to randomisation to follow-up visit.

In addition, as a risk mitigation strategy, if the patient experiences an intolerable increase in diseases activity of psoriatic arthritis during the course of the trial treatment, the patient will be discontinued from the trial treatment and will receive a standard of care treatment as deemed appropriate by the investigator. Examples of standard of care that patients may be offered are approved injectable biologic drugs (such as TNF-alpha inhibitors or IL-17 inhibitors) or oral medication (such as apremilast or tofacitinib), methotrexate, paracetamol and non-steroidal anti-inflammatory drugs. The patient will be offered this standard of care for the duration with which they require it.
Control group
Placebo

Outcomes
Primary outcome [1] 324766 0
Response to treatment assessed as >/= 20% change in symptoms determined by the American College of Rheumatology rheumatoid arthritis response to treatment criteria (ACR). The ACR criteria is a validated criteria and is a composite endpoint as it requires assessment of a number of different factors, It involves both a physical assessment and also the completion of questionnaires by both the patient and assessor. ACR is assessed as at least 20% improvement in swollen joint count compared to baseline, at least 20% improvement in TJC* compared to baseline and a least 20% improvement in at least 3 out of the following 5 variables:
Patient’s assessment of pain on VAS (patient questionnaire )
Patient’s global assessment of the disease on VAS (patient questionnaire)
Investigator’s global assessment of the disease on VAS (questionnaire)
Patient’s assessment of disability on HAQ (patient questionnaire)
Acute phase reactant (serum CRP) (blood test)
Timepoint [1] 324766 0
Baseline, Day 1, Week 1, Week 2, Week 4 and Week 8, Week 12 and then one month post-completion of intervention period
Secondary outcome [1] 385708 0
Response to treatment assessed as >/= 50% change in symptoms determined by the American College of Rheumatology rheumatoid arthritis response to treatment criteria (ACR). The ACR criteria is a validated criteria and is a composite endpoint as it requires assessment of a number of different factors, It involves both a physical assessment and also the completion of questionnaires by both the patient and assessor. ACR is assessed as at least 50% improvement in swollen joint count compared to baseline, at least 50% improvement in TJC* compared to baseline and a least 50% improvement in at least 3 out of the following 5 variables:
Patient’s assessment of pain on VAS (patient questionnaire )
Patient’s global assessment of the disease on VAS (patient questionnaire)
Investigator’s global assessment of the disease on VAS (questionnaire)
Patient’s assessment of disability on HAQ (patient questionnaire)
Acute phase reactant (serum CRP) (blood test)
Timepoint [1] 385708 0
Baseline, Day 1, Week 1, Week 2, Week 4 and Week 8, Week 12 and then one month post-completion of intervention period
Secondary outcome [2] 387265 0
Response to treatment assessed as >/= 70% change in symptoms determined by the American College of Rheumatology rheumatoid arthritis response to treatment criteria (ACR). The ACR criteria is a validated criteria and is a composite endpoint as it requires assessment of a number of different factors, It involves both a physical assessment and also the completion of questionnaires by both the patient and assessor. ACR is assessed as at least 70% improvement in swollen joint count compared to baseline, at least 50% improvement in TJC* compared to baseline and a least 70% improvement in at least 3 out of the following 5 variables:
Patient’s assessment of pain on VAS (patient questionnaire )
Patient’s global assessment of the disease on VAS (patient questionnaire)
Investigator’s global assessment of the disease on VAS (questionnaire)
Patient’s assessment of disability on HAQ (patient questionnaire)
Acute phase reactant (serum CRP) (blood test)
Timepoint [2] 387265 0
Baseline, Day 1, Week 1, Week 2, Week 4 and Week 8, Week 12 and then one month post-completion of intervention period
Secondary outcome [3] 387266 0
Response will be measured by change in Tender Joint Count at Week 12 as compared to baseline
Timepoint [3] 387266 0
Baseline, Day 1, Week 1, Week 2, Week 4 and Week 8 and Week 12
Secondary outcome [4] 387268 0
Response will be measured by change in Swollen Joint Count at Week 12 as compared to baseline.
Timepoint [4] 387268 0
Baseline, Week 1, Week 2, Week 4 and Week 8 and Week 12
Secondary outcome [5] 387269 0
Change in patient's physical function/disability determined by patient completion of the twenty- item Health Assessment Questionnaire Disability Index (HAQ-DI).
Timepoint [5] 387269 0
Baseline, Week 1, Week 2, Week 4 and Week 8, Week 12 and then one month post-completion of intervention period
Secondary outcome [6] 387270 0
Response to treatment for patients with a greater than or equal to 3% baseline psoriasis body surface area assessed according to the Psoriasis Area and Severity Index (PASI75). Four areas of the patient's skin will be reviewed and assessed for psoriasis at Week 12.
Timepoint [6] 387270 0
PASI will be assessed at Day 1, Week 1, Week 4 and Week 8 and Week 12.
Secondary outcome [7] 387271 0
The safety of the treatment will be assessed by the number of adverse events (AE)s, treatment urgent AEs, Serious AEs (SAEs), intensity of the events assessed according to the Rheumatology Common Toxicity Criteria (RCTC) version 2.0), measurement of patient vital signs and safety laboratory values.
Timepoint [7] 387271 0
Baseline, Day 1, Week 1, Week 2, Week 4, Week 8, Week 12 and one month post completion of treatment
Secondary outcome [8] 387272 0
Tolerability of the treatment will be assessed by the number of patients who discontinue drug due to drug-related adverse events.
Timepoint [8] 387272 0
Baseline, Day 1, Week 1, Week 2, Week 4 and Week 8 and Week 12

Eligibility
Key inclusion criteria
- Males or females, aged >/= 18 years and <= 75 years at screening
- Have PsA symptoms for at least 6 months prior to screening, as assessed by the investigator
- Have PsA on the basis of the CASPAR with peripheral symptoms at screening visit, as assessed by the investigator
- Have at least 3 tender joints and at least 3 swollen joints at screening and randomisation visits, as assessed by the investigator
- At least one PsO skin or nail lesion or a documented personal history of PsO at screening, as assessed by the investigator
- Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Major chronic inflammatory or connective tissue disease other than PsA (e.g. rheumatoid arthritis, systemic lupus
erythematosus, ankylosing spondylitis, Lyme disease, gout) or fibromyalgia, as assessed by the investigator
- Active uveitis or uveitis within 4 weeks prior to randomisation disease assessed by the investigator
- Suspected or diagnosed inflammatory bowel disease assessed by the investigator
- Previous exposure to BI 730357
- Prior use of any therapeutic agent directly targeted to IL-12/23, IL-23 or IL-17
- Prior use of more than two different TNFi agents

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer-based Interactive Web Response System will be performed at Visit 2.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
After the assessment of all in- and exclusion criteria, each eligible patient will be randomised to treatment groups according to a randomisation plan in a 1:1:1:1 ratio stratified based on:
- prior TNF inhibitor use. The proportion of patients with previous TNF inhibitor use will be capped at 30%.
- concurrent methotrexate use (yes or no),
- Location of clinical sites: Japan and other countries and
- patient participation to MRI sub-study (yes or no) Australia and New Zealand are not taking part in the MRI sub-study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
The main objectives of this study are to assess efficacy, safety and tolerability of BI 730357 in treatment of patients with active PsA. The proof-of-clinical-concept (PoCC) and doseranging will be achieved through the primary endpoint comparison (ACR 20 rates at Week12). For this purpose, the primary analysis uses methodology for PoCC and doseranging employing both multiple comparison procedures and modelling techniques (MCPMod).

The following patient analysis sets are defined:
The efficacy analyses will be based on the intent-to-treat principle, comprising all
participants who were randomised and received at least one dose during the trial. The
efficacy analyses will be based on the planned treatment; this set of patients is called the
Full Analysis Set (FAS). Safety analyses will be based on the actual treatment received; this set of patients is called the Treated Set (TS). Data from patients who were screened but not randomised will be listed but not included in any summary or inferential statistics.
Specifications of important protocol deviations will be provided in the TSAP.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
4/04/2022
Actual
Date of last participant enrolment
Anticipated
31/03/2023
Actual
Date of last data collection
Anticipated
3/07/2023
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS
Recruitment outside Australia
Country [1] 22828 0
New Zealand
State/province [1] 22828 0
Auckland
Country [2] 22829 0
United Kingdom
State/province [2] 22829 0
Country [3] 22830 0
Belgium
State/province [3] 22830 0
Country [4] 22831 0
Luxembourg
State/province [4] 22831 0
Country [5] 22832 0
Poland
State/province [5] 22832 0
Country [6] 22833 0
Czech Republic
State/province [6] 22833 0
Country [7] 22834 0
Spain
State/province [7] 22834 0
Country [8] 22835 0
Germany
State/province [8] 22835 0
Country [9] 22836 0
Ukraine
State/province [9] 22836 0
Country [10] 22837 0
Hungary
State/province [10] 22837 0
Country [11] 22838 0
Moldova, Republic Of
State/province [11] 22838 0
Country [12] 22839 0
Georgia
State/province [12] 22839 0
Country [13] 22840 0
United States of America
State/province [13] 22840 0
Country [14] 22841 0
Japan
State/province [14] 22841 0
Country [15] 22842 0
Mexico
State/province [15] 22842 0
Country [16] 22843 0
Russian Federation
State/province [16] 22843 0
Country [17] 22844 0
Bulgaria
State/province [17] 22844 0

Funding & Sponsors
Funding source category [1] 306465 0
Commercial sector/Industry
Name [1] 306465 0
Boehringer Ingelheim Pty Ltd
Country [1] 306465 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim Pty Ltd
Address
Level 1, 78 Waterloo Rd, North Ryde, NSW 2113, Australia
Country
Australia
Secondary sponsor category [1] 306986 0
None
Name [1] 306986 0
None
Address [1] 306986 0
Country [1] 306986 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306670 0
Bellberry HREC
Ethics committee address [1] 306670 0
123 Glen Osmond Rd, Eastwood SA 5063, Australia
Ethics committee country [1] 306670 0
Australia
Date submitted for ethics approval [1] 306670 0
24/08/2020
Approval date [1] 306670 0
26/11/2020
Ethics approval number [1] 306670 0
Ethics committee name [2] 306673 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [2] 306673 0
Research & Education Network building
Darcy Rd
Westmead Hospital
Westmead NSW 2145
Ethics committee country [2] 306673 0
Australia
Date submitted for ethics approval [2] 306673 0
27/08/2020
Approval date [2] 306673 0
19/11/2020
Ethics approval number [2] 306673 0

Summary
Brief summary
This trial is designed to evaluate safety, tolerability, PK and PD of BI 730357 in male and female patients with psoriatic arthritis using multiple escalation schemes and doses, and will support dose selection for phase 3 clinical development of BI 730357. Although effective treatments for psoriatic arthritis are approved, the unmet medical need remains for safer oral therapy that works well, improves joint and skin inflammation, prevents structural damage and maintains the efficacy over time.

This trial is a randomised, double-blind, placebo-controlled trial in which three dose regiments of BI 730357 will be compared to placebo over a 12-week treatment period. Only approximately 40 patients out of total 160 patients will be randomized to receive placebo treatment. A placebo-control design is required for evaluation of evaluation of BI 730357 efficacy and safety. In addition, a placebo arm is needed in order to avoid potential confounding factors, such as placebo effect, potential investigator bias in safety and efficacy assessment or regression to the mean in endpoint scoring. In addition, as a risk mitigation strategy, if the patient experiences an intolerable increase in diseases activity of psoriatic arthritis during the course of the trial treatment, the patient will be discontinued from the trial treatment and will receive a standard of care treatment as deemed appropriate by the investigator.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104622 0
Dr Jane Zochling
Address 104622 0
Southern Clinical Research
4 Warneford Street,
Hobart TAS 7000
Australia
Country 104622 0
Australia
Phone 104622 0
+61362238802
Fax 104622 0
Email 104622 0
[email protected]
Contact person for public queries
Name 104623 0
Dr Jane Zochling
Address 104623 0
Southern Clinical Research
4 Warneford Street,
Hobart TAS 7000
Australia
Country 104623 0
Australia
Phone 104623 0
+61362238802
Fax 104623 0
Email 104623 0
[email protected]
Contact person for scientific queries
Name 104624 0
Mrs Fiona Shepheard
Address 104624 0
Boehringer Ingelheim Pty Ltd
Level 1, 78 Waterloo Rd, North Ryde, NSW 2113, Australia
Country 104624 0
Australia
Phone 104624 0
+61288758774
Fax 104624 0
Email 104624 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
8810Clinical study report    A lay summary of the results of the clinical trial... [More Details]



Results publications and other study-related documents

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