A Phase II, Clinical Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of LNP1955 in Patients with Moderate to Severe Rheumatoid Arthritis.

• Register: EUCTR
• Last refreshed on: 30 October 2017
• Main ID: EUCTR2016-001532-35-HU
• Date of registration: 15/06/2016
• Prospective Registration: Yes
• Primary sponsor: Lupin Limited
• Public title: A Phase II, Clinical Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of LNP1955 in Patients with Moderate to Severe Rheumatoid Arthritis.
• Scientific title: A Phase II, Dose Ranging, Exploratory Clinical Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of LNP1955 in Patients with Moderate to Severe Rheumatoid Arthritis.
• Date of first enrolment: 08/08/2016
• Target sample size: 64
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001532-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: The study has 2 parts. Main part is randomised and MTX addon part is open label If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Hungary

Contacts

• Name: Project Director
• Affiliation: Lupin Limited

• Name: Project Director
• Affiliation: Lupin Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Patients will be entered in the study only if they meet all of the following criteria
1.All patients must sign and date an informed consent form consistent with International Council for Harmonisation Good clinical practice (ICH GCP) guidelines and local legislation prior to participation in the trial (i.e., prior to any trial procedures) and be willing to follow the protocol.
2.Ambulatory male or female participants, between 18 and 65 years of age, meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for RA; with at least 6 swollen joints (66 joint count) and at least 6 tender joints (68 joint count).
3.Moderate to severe RA with DAS28 score =3.2 (based on swollen joint count (SJC)/TJC using 28 joints).
4.Patients with RA who are treatment naïve or who have failed therapy with at-least 1 DMARD: non-biologic/biologic, due to lack of efficacy or toxicity.
5.Patient should not have received biologic therapy for at least 6 months prior to first dose of IP.
6.Patient has completed washout of minimum 7 days for Azathioprine, Sulfasalazine and Cyclosporine, 4 weeks for hydroxychloroquine and Auranofin (oral gold), and 6 weeks for MTX (except for MTX Add on part) prior to first dose of IP.
7.Patients who have not taken leflunomide within 2 months, unless the patient has completed a Cholestyramine washout at least 4 weeks prior to first dose of IP.
8.Patients who have not taken alkylating agents (e.g., cyclophosphamides) within 6 months prior to first dose of IP.
9.Participants of reproductive potential (males and females), must be willing to use a reliable means of contraception (e.g., combined or progesterone only hormonal contraception, intrauterine devices, surgical sterilization, double barrier methods, or vasectomized partner) throughout trial participation and 2 months after the last dose of IP OR Women if postmenopausal (aged greater than 45 years) must have a history of amenorrhea for at least 1 year from the time of last menstrual cycle and have follicle stimulating hormone (FSH) value indicating menopause with high reliability.
Additional Inclusion Criteria for MTX Add on part:
1.Patients who are MTX naïve and eligible to receive 7.5 mg MTX per week after having tolerated at least one dose; (OR) Patients who are on stable dose of MTX 7.5 mg/week.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
Patients will not be entered in the study for any of the following reasons:
1.Patients who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care).
2.Primary or secondary immunodeficiency (e.g., human immunodeficiency virus [HIV]). Evidence of positive serology for hepatitis B (HBsAg) or hepatitis C.
3.Patients with active tuberculosis (TB), prior history of incompletely treated TB, latent TB or evidence of TB as shown positive by QuantiFERON® TB Gold test or appropriate test or those who are at risk of developing TB.
4.Evidence of coronary artery disease or cardiac arrhythmias or severe congestive heart failure (New York Heart Association Classes III and IV), history of stroke, uncontrolled hypertension (systolic blood pressure [BP] =160 mmHg and diastolic BP =95 mmHg) or any clinically significant abnormalities in the ECG.
5.Treatment with intra-articular or systemic corticosteroids within 4 weeks prior to the first dose of IP (except oral doses = 10.0 mg prednisolone daily or equivalent.
6.History of malignancy within 5 years prior to the Screening Visit, except curatively treated basal cell carcinoma or squamous cell carcinoma of the skin and Grade 1 cervical cancer.
7.Patient has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, and thrombocytopenia), renal, or liver disease (e.g., fibrosis, cirrhosis, and hepatitis), or gastroenteric ulcer or any other uncontrolled disease or has clinically relevant deviations in laboratory tests at Screening such as the following:
-Serum transaminases, alanine transaminase (ALT) and/or aspartate transaminase (AST) >3 times upper limit of normal (ULN).
-Bilirubin >2 times ULN.
-Alkaline phosphatase (ALP) >3 times ULN.
-Renal insufficiency as defined by creatinine level =1.5 mg/dL (132 µmol/L) for females or = 2.0 mg/dL (177 µmol/L) for males.
-Albumin -Platelets < 100×109/L (<100,000/mm3).
-White blood cell count < 3.5×109/L.
-Neutrophil count < 2000×106/L (<2000/mm3).
-Hemoglobin level = 8 gm/dL.
-Glycosylated hemoglobin level = 8%.
8.Receipt of live/attenuated vaccinations within 30 days prior to the first dose of IP or planned vaccinations throughout the study or 30 days after study completion.
9.History of known and significant drug allergies (such as Steven-Johnson syndrome, anaphylaxis) or any hypersensitivities that can have potential impact on patient’s participation as determined by the Investigator.
10.Have current or recent history of a severe, progressive, or uncontrolled disease, which in the opinion of Investigator makes the patient inappropriate for inclusion in this study.
11.History of, or current, other rheumatic diseases, autoimmune inflammatory joint disease other than RA (e.g., gout, psoriatic arthritis, and Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, or Felty’s syndrome, scleroderma, inflammatory myopathy, mixed connective tissue disease, or any overlap syndrome). Secondary Sjögren’s syndrome or secondary limited cutaneous vasculitis with RA is permitted.
12.Any major surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to the Screening visit or planned during the study period or patients with a history of septic arthritis of any joints within 12 months prior to sc

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to Severe Rheumatoid Arthritis.
MedDRA version: 19.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Code: LNP1955
Pharmaceutical Form: Capsule, soft
Current Sponsor code: LND400111
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at Week 12

Secondary Objective: •To assess the pharmacodynamics (PD) and safety of LNP1955 in comparison to placebo;
•To explore the pharmacokinetics (PK) of LNP1955 and synergy with MTX in patients with moderate to severe RA in an open label study arm.

Main Objective: •The primary objective is to assess the proof of efficacy of LNP1955 and find an optimum dose in patients with moderate to severe rheumatoid arthritis (RA).

Timepoint(s) of evaluation of this end point: 12 weeks after treatment

Secondary Outcome(s)

Secondary end point(s): • The proportion of patients meeting ACR20 response criteria after 4 weeks and 8 weeks of treatment.
• The proportion of patients meeting ACR50 and ACR70 response after 4 weeks, 8 weeks, and 12 weeks of treatment.
• The change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Week 4, Week 8, and Week 12.

Timepoint(s) of evaluation of this end point: after 4 and 8 weeks of treatment for ACR 20
4,8 and 12 weeks after treatment for ACR 50 and ACR 70
4, 8 and 12 weeks from baseline for DAS28 (CRP)and DAS 28( ESR)

Secondary ID(s)

LRP/LNP1955/2016/002

Source(s) of Monetary Support

Lupin Limited