| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe chronic plaque psoriasis |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | Psoriasis |
|
| 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 |
| To compare the short term and long-term clinical efficacy, safety and tolerability of ABT-874 compared to MTX in the treatment of moderate to severe chronic plaque psoriasis over a 52-week period. |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Males and females 18 years of age and over.
2. Clinical diagnosis of psoriasis for at least 6 months as determined by subject
interview of his/her medical history and confirmation of diagnosis through
physical examination by the Principal Investigator.
3. Stable plaque psoriasis for at least 2 months before Screening and at Baseline
(Week 0) visits as determined by subject interview of his/her medical history.
4. Moderate to severe plaque psoriasis defined by ≥ 10% Body Surface Area (BSA)
involvement at the Baseline (Week 0) visit.
5. PGA of at least moderate disease (defined as PGA ≥ 3) at the Baseline (Week 0)
visit.
6. PASI score of ≥ 12 at the Baseline (Week 0) visit.
7. Subject is a candidate for systemic therapy or phototherapy and has active psoriasis despite treatment with topical agents.
8. Women are eligible to participate in the study if they meet one of the following
criteria:
● Women of childbearing potential must undergo monthly pregnancy testing
during the study and agree to use two of the following methods of
contraception throughout the study and for 6 months after the last dose of study
drug:
○ Oral contraceptives;
○ Transdermal contraceptives;
○ Injectable or implantable methods;
○ Intrauterine devices; and
○ Barrier methods (diaphragm with spermicide, condom with spermicide).
Subjects using oral or parenteral forms of contraceptives must have been
practicing birth control for at least three months prior to study drug
administration.
● Women who are postmenopausal (for at least one year), sterile, or
hysterectomized;
● Women who have undergone tubal ligation will be required to undergo
monthly pregnancy testing during the duration of the study and agree to use a
second form of contraception which includes:
○ Oral contraceptives;
○ Transdermal contraceptives;
○ Injectable or implantable methods;
○ Intrauterine devices; and
○ Barrier methods (diaphragm with spermicide, or condom with
spermicide).
9. Sexually active males subjects (including males who have had a vasectomy) are able to participate in the study if they use effective contraception (ie condoms with spermicide) during the study and for 6 months after study completion.
10. Subject is judged to be in good general health as determined by the Principal
Investigator based upon the results of medical history, laboratory profile, physical
examination, chest X-ray (CXR), and 12-lead electrocardiogram (ECG) performed
at Screening.
11. Able and willing to give written informed consent and to comply with the
requirements of this study protocol.
|
|
| E.4 | Principal exclusion criteria |
1. Previous exposure to systemic anti-IL-12 therapy, including ABT-874.
2. Subject has previous exposure to MTX.
3. Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis,
medication-induced or medication-exacerbated psoriasis, or new onset guttate
psoriasis.
4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or
viral) that may interfere with evaluation of psoriasis.
5. History of an allergic reaction or significant sensitivity to constituents of study
drug (See Section 5.5.2 of the study protocol).
6. Cannot discontinue topical therapies for the treatment of psoriasis such as
corticosteroids, vitamin D analogs, or retinoids at least 2 weeks prior to the
Baseline (Week 0) visit and during the study. Subjects are allowed to use:
● Shampoos that contain no corticosteroid;
● Bland (without beta or alpha hydroxy acids) emollients;
● Low potency (Class VI or Class VII) topical corticosteroids on the palms,
soles, face, inframammary area, and groin only. See Appendix O for a listing
of examples of Class VI or VII topical corticosteroids.
7. Cannot avoid UVB phototherapy for at least 2 weeks prior to the Baseline
(Week 0) visit and during the study.
8. Cannot avoid PUVA phototherapy for at least 4 weeks prior to the Baseline
(Week 0) visit and during the study.
9. Cannot discontinue systemic therapies for the treatment of psoriasis, or systemic
therapies known to improve psoriasis, during the study. See study protocol for further details.
10. Subject is taking or requires oral or injectable corticosteroids during the study.
Inhaled corticosteroids for stable medical conditions are allowed.
11. Poorly controlled medical condition, such as uncontrolled diabetes with
documented history of recurrent infections, unstable ischemic heart disease,
congestive heart failure, recent cerebrovascular accidents and any other condition,
which, in the opinion of the Investigator or medical monitor, would put the subject at risk by
participation in the study.
12. Subject has a history of clinically significant hematologic (e.g. severe anemia,
leukopenia, thrombocytopenia), renal or liver disease (e.g. fibrosis, cirrhosis,
hepatitis).
13. Subject has infection or risk factors for severe infections, for example:
● Excessive immunosuppression or other factors associated with it, including
human immunodeficiency virus infection;
● Severe, recurrent, or persistent infections such as Hepatitis B or C;
● Active tuberculous disease;
● Evidence of latent tuberculosis (TB) infection demonstrated by Purified
Protein Derivative (PPD) ≥ 5 mm of induration and/or chest X-ray (CXR)
findings suggestive of latent TB; EXCEPT if prophylactic treatment, as
recommended by local guidelines, is initiated prior to administration of study
drug or there is documentation that the subject has received prophylactic
treatment for TB previously, see Appendix D of the study protocol (US Center for Disease Control [CDC] Treatment Recommendations for Positive PPD Tuberculosis
Information - Treatment of Latent TB Infection);
● Any other significant infection requiring hospitalization or intravenous (IV)
antibiotics in the month prior to Screening;
● Infection requiring treatment with antibiotics in the two weeks prior to
Screening;
● Subject has received vaccination with Bacille Calmette-Guerin (BCG) within
12 months prior to Screening;
● Subject has received vaccination with a live viral agent one month prior to
Screening or will require vaccination during study participation including up
to one month after the last dose of study drug.
14. History of malignancies other than successfully treated basal cell carcinoma, nonmetastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ.
15. History of major immunologic reaction (such as serum sickness or anaphylactoid
reaction) to an Immunoglobulin G containing agent (such as IV gamma globulin, a
fusion protein, or monoclonal antibody).
16. Exacerbation of asthma requiring hospitalization in the ten years prior to Screening (subjects with asthma not requiring hospitalization should be discussed with the Medical Monitor prior to Baseline [Week 0]).
17. Female subject who is pregnant or breast-feeding or considering becoming
pregnant during the study or for 6 months after study completion.
18. Screening clinical laboratory analyses show abnormal results. See study protocol for further details.
19. Recent history of substance abuse or psychiatric illness that could preclude
compliance with the protocol.
20. Subject has a known allergic hypersensitivity to MTX.
21. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption.
22. For any reason, subject is considered by the Principal Investigator to be an
unsuitable candidate to receive ABT-874.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. The proportion of subjects who achieve a PASI 75 response defined as 75% reduction in PASI score relative to Baseline at Week 24
2. The proportion of subjects who achieve a PGA score of 0 or 1 at Week 24
3. The proportion of subjects who achieve a PASI 75 response defined as at least 75% reduction in PASI score relative to Baseline at Week 52
4. The proportion of subjects who achieve a PGA score of 0 or 1 at Week 52
|
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| E.8.2.3 | Other | No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 43 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| The date of the last subject's last scheduled visit or the actual date of the follow-up contact, whichever is longer. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 18 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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