| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Psoriatic arthritis (PsA) |
|
| E.1.1.1 | Medical condition in easily understood language |
| PsA is a chronic, inflammatory form of arthritis associated with psoriasis. The symptoms are oligoarthritis or polyarthritis, pain, swelling, tenderness and rigidity of soft tissues around the joint. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037160 |
| E.1.2 | Term | Psoriatic arthritis |
| E.1.2 | System Organ Class | 100000004859 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to demonstrate the equivalence of BAT2506 and Simponi® on the efficacy parameter, American College of Rheumatology (ACR) 20 response, in participants with active PsA. |
|
| E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of BAT2506 with Simponi® on additional efficacy parameters in participants with active PsA;
- To compare the PK and PD parameter of BAT2506 with Simponi® in participants with active PsA;
- To compare the safety of BAT2506 with Simponi®;
- To compare the immunogenicity and of BAT2506 with Simponi®
- To assess safety and immunogenicity following transition from Simponi® to BAT2506
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Receipt of a signed/dated informed consent.
•Male or female, aged from 18 to 80 years at Screening.
•PsA for at least 6 months prior to the first IMP dose and compliance with CASPAR at Screening.
•Active PsA defined by the presence of ≥3 of 68 tender joint counts and ≥3 of 66 swollen joint counts at Screening and Randomization.
•Active PsA at Screening despite previous DMARD or NSAID therapy. DMARD therapy is defined as taking a DMARD for at least 3 months, or
evidence of DMARD intolerance. NSAID therapy is defined as taking an NSAID for at least 4 weeks (or have intolerance to or contraindication to
NSAID therapy).
•At least 1 active psoriatic lesion with a qualifying lesion of at least 2 cm in diameter at Screening and Randomization.
•Subject is negative for rheumatoid factor and ACCP antibodies at Screening.
•Female subjects must be: Postmenopausal OR Permanently sterilized OR If of childbearing potential, must be willing to use a highly effective
method of contraception throughout the study until 6 months after last IMP dose, and must have a negative pregnancy test at Screening and
immediately prior to the first dose. Please see "Inclusion criteria".
•Men capable of fathering children must be using adequate birth control measures during the study and for 6 months after receiving the IMP
dose.
•TB testing at the study central lab. (QuantiFERON TB Gold) during the Screening. Eligibility criretia:
-No history of latent or active TB prior to Screening,
-No signs or symptoms suggestive of active TB upon medical history
and/or physical examination.
-No recent close contact with a person with active TB or, if there has
been such contact, will be referred to a physician specializing in TB to
undergo additional evaluation and, if warranted, receive appropriate
treatment for latent TB prior to the first IMP dose, started at least 4
weeks prior to the first dose of study drug and the TB prophylaxis
continues to completion per local TB medical guidelines.
-Either negative diagnostic TB test result (QuantiFERON-TB Gold); or newly identified positive diagnostic TB test result (or 2 indeterminate
test results) during Screening where active TB has been ruled out, and appropriate treatment for latent TB has been finished within 3 years
prior to the first dose of IMP, or this therapy started at least 4 weeks prior to the first dose and the TB prophylaxis continues to completion
per local TB medical guidelines.
-A chest radiograph (both posterior anterior and lateral views), taken within 3 months prior to the first IMP dose and read by a qualified
radiologist and/or pulmonologist, with no evidence of current active TB or old inactive TB.
•If using MTX, the treatment should be started at least 3 months prior to the first IMP dose and in case of no serious toxic side effects to MTX.
MTX routes of administration and doses (not to exceed 25 mg/week) should be stable for at least 4 weeks prior to the first dose of IMP and
throughout the study. If not currently used, it must not have to be received for at least 4 weeks prior to the first dose of IMP.
•In case of use of NSAIDs, including selective cyclooxygenase (COX) 2 inhibitors, and other analgesics, he/she must be on a stable dose for at
least 2 weeks prior to the first dose of IMP.
•If NSAIDs/COX 2 inhibitors/other analgesics are not currently used, he/she must not have received NSAIDs/analgesics for at least 2 weeks
prior to the first administration of the study drug.
•If oral corticosteroids are used, it must not be used for at least 4 weeks prior to Screening with a stable dose equivalent to ≤10 mg of
prednisone/day for at least 2 weeks prior to the first IMP dose. If not currently used, oral corticosteroids must not be used for at least 2 weeks
prior to the first IMP dose.
•Participant must be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at
Screening.
•Screening laboratory test results within the parameters defined in protocol ("Inclusion criteria"). Must be medically stable based on these
tests. If the results of the serum chemistry panel, incl. liver enzymes or hematology are outside the normal ranges, please refer to details given
in "Incl. criteria" of protocol.
•No prolonged sun exposure, tanning booths or other ultraviolet light sources during the study.
•Adherence to the prohibitions and restrictions specified in protocol.
|
|
| E.4 | Principal exclusion criteria |
•Current or previous receipt of any biological agent or targeted DMARDs for the treatment of PsA or psoriasis.
•Receipt of any other nonbiological DMARDs (apart from MTX), including sulfasalazine, hydroxychloroquine or apremilast within 8 weeks prior to
the first drug administration, or has previously received leflunomide within 12 weeks (except at least 4 weeks prior to the first study drug
dose, the subject has documented completion of standard cholestyramine or activated charcoal washout procedure).
•Epidural, intra-articular, intramuscular, or IV corticosteroids during the 4 weeks prior to first IMP administration.
•Treatment with cytotoxic agents, (including but not limited to azathioprine, cyclosporine, cyclophosphamide), nitrogen mustard,
chlorambucil, or other alkylating agents within 6 months prior to the dose administration.
•Receipt of PUVA or systemic retinoids within 4 weeks prior to the first dose administration.
•Topical treatments for psoriasis (eg, corticosteroids, keratolytics, coal tar, anthralin, vitamin D3 analogues, or topical tacrolimus, and retinoids)
within 2 weeks prior to the first dose of IMP.
•Any complementary therapies including ayurvedic medicine, traditional Chinese medication(s), acupuncture, or other unapproved medication for
the treatment of PsA within 4 weeks prior to the first dose.
•BCG vaccination received within 12 months prior Screening or expected to be received during the study or within 12 months following last IMP
dose.
•Any live vaccinations received or planned to be received from 3 months before first dose of IMP and up to 3 months after the last IMP dose.
•Other therapeutic infectious agents received within 8 weeks prior to first dose or expected to receive other therapeutic infectious agents
during the study until SFU.
•IV immunoglobulins or plasmapheresis received within 6 months prior to the first dose of IMP.
•Current participation in another study of a medication (systemic) under investigation. Previous participation in another study of a medication
(systemic) under investigation within 12 weeks or at least 5 half-lives prior to the first administration of IMP, whichever is longer.
•Previous participation in another study of a medical device under investigation within 4 weeks prior to the Screening Visit or current
participation in another study of a medical device under investigation.
•Subject has a history of substance abuse.
•A diagnosis of inflammatory conditions other than psoriasis or PsA including, but not limited to rheumatoid arthritis, sarcoidosis, systemic
lupus erythematosus, reactive arthritis, and Lyme disease.
•An active infection or history of infections as follows:
-Any active infection (except common cold) within 2 weeks prior to the first dose.
-An infection, treated with an IV anti-infective within 2 months or oral anti infectives within 2 weeks prior to the first dose.
-A history of opportunistic, recurrent or chronic infections that might cause this study to be detrimental to the participant.
•Concurrent acute or chronic viral hepatitis B or C or HIV infection. For details please refer to "Excl.criteria' section in Protocol.
•Acute anterior uveitis within 6 weeks prior to the first dose of IMP.
•Clinical signs and symptoms consistent with COVID-19, within the last 4 weeks prior to Screening or during Screening.
•Severe course of COVID-19.
•A history of hypersensitivity to human Ig proteins or other components of golimumab.
•A major surgery (including joint surgery) which took place within the 3 months prior to the first dose, or a planned surgery during the study.
•Myocardial infarction or stroke within the 6 months prior to the Screening.
•Fibromyalgia or osteoarthritis symptoms that may have potential to interfere with efficacy assessments.
•A known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease,
such as lymphadenopathy of unusual size or location, clinically significant splenomegaly, or monoclonal gammopathy of undetermined
significance.
•A history of known demyelinating diseases such as multiple sclerosis or optic neuritis.
•A history of malignancy (exceptions are given in protocol section "Excl.criteria').
•Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk to participate in the
study, or confounds the ability to interpret data from the study.
•Any systemic disease (ie, cardiovascular, neurological, renal, liver, metabolic, gastrointestinal, hematological, immunological, etc)
considered to be uncontrolled, unstable, or likely to progress to a clinically significant degree during the course of the study.
•Any other unsuitable condition (medical or psychiatric).
•Pregnancy, nursing, or planning pregnancy or fathering within 6 months after last dose of IMP.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| ACR 20 response at Week 8 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- ACR 20/50/70 over time
- PASI 75/PASI 90/PASI 100 response over time (in a subset of participants with at least 3% body surface area psoriasis involvement at baseline)
- Change from baseline in DAS28-CRP over time
- DAS28 CRP response (good or moderate response) over time
- Change from baseline in HAQ DI over time
- Change from baseline in NAPSI over time
- Change from baseline in ACR core components: swollen joint count, tender joint count, Patient's assessment of Arthritis Pain
(VAS), Participant's Global Assessment of Disease Activity (VAS), Physician's Global Assessment of Disease Activity (VAS), HAQ-DI, and
CRP over time
- Change from baseline in PASI over time.
- PK parameters; truncated AUC after first administration until second administration (AUC0 t), AUC over dosage interval at steady state (AUC0
τ), maximum concentration at steady state (Cmax) and trough concentration before next dosing of study drug at steady state
(Ctrough), determined using a population PK modeling approach.
- Change from baseline in CRP over time. Impact of CRP changes on efficacy and safety.
- AEs, clinical laboratory values, vital signs, ECG, injection site reactions.
- Incidence of ADAs (including an estimate of titer), and neutralizing antibodies overal and overtime. Assessment of the impact of immunogenicity on PK, efficacy, and safety.
- Incidence of AE, ADAs, neutralizing antibodies. Assessment of the impact of immunogenicity on PK, efficacy, and safety. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please refer to section E.5.2 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| China |
| Russian Federation |
| Ukraine |
| Poland |
| Bulgaria |
| Czechia |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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