A PHASE 11, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER, WORLDWIDE, DOSE-RANGING CLINICAL TRIAL WITH A PROOF-OF-CONCEPT LEAD COHORT TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF MK-8457 + MTX IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS DESPITE METHOTREXATE THERAPY

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-036-12
• Date of registration: 06/11/2012
• Prospective Registration: Yes
• Primary sponsor: MERCK SHARP & DOHME PERU S.R.L.,
• Public title: A PHASE 11, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER, WORLDWIDE, DOSE-RANGING CLINICAL TRIAL WITH A PROOF-OF-CONCEPT LEAD COHORT TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF MK-8457 + MTX IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS DESPITE METHOTREXATE THERAPY
• Scientific title: A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER, WORLDWIDE, DOSE-RANGING CLINICAL TRIAL WITH A PROOF-OF-CONCEPT LEAD COHORT TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF MK-8457 + MTX IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS DESPITE METHOTREXATE THERAPY
• Target sample size: 30
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=036-12
• Study type: Interventional
• Study design: THIS IS A PHASE IT, MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, WORLDWIDE STUDY TO ASSESS THE SAFETY, TOLERABILITY, AND EFFICACY OF MK-8457 IN SUBJECTS WITH ACTIVE RA DESPITE MTX TREATMENT.
• Phase: II

Countries of recruitment

Canada, Chile, Denmark, Germany, Hungary, Japan, Korea North, Lithuania, Peru, Poland, South Africa, United Kindgdom, United States

Contacts

• Name: Rodolfo Alarcon Lozano
• Affiliation: MERCK SHARP & DOHME PERU S.R.L

• Name: Rodolfo Alarcon Lozano
• Affiliation: MERCK SHARP & DOHME PERU S.R.L

Key inclusion & exclusion criteria

Inclusion criteria:
1. SUBJECT MUST BE ≥ 18 YEARS OF AGE ON THE DAY OF SIGNING THE INFORMED CONSENT.
RA DIAGNOSIS AND DISEASE ACTIVITY:
2. SUBJECT HAS A DIAGNOSIS OFRA (ACCORDING TO REVISED 1987 CRITERIA OFTHE ARA) FOR AT LEAST 6 MONTHS PRIOR TO SCREENING. (SEE APPENDIX 6.3)
3. SUBJECT HAS ACTIVE RA AS DEFINED BY THE PRESENCE OF 6 SWOLLEN JOINTS (OF 66 JOINT COUNT) AND 6 TENDER JOINTS (OF 68 JOINT COUNT) AT SCREENING (VISIT 1) AND BASELINE (VISIT 2).
4. SUBJECT HAS A C-REACTIVE PROTEIN (CRP) BLOOD LEVEL > 0.9 MG/DL FROM THE CENTRAL REFERENCE LABORATORY AT SCREENING. (SEE APPENDIX 6.3)
5. SUBJECT IS ANTI-CYCLIC CITRULLINATED ANTIBODY POSITIVE AND/OR RHEUMATOID FACTOR POSITIVE AT SCREENING. (SEE APPENDIX 6.3)
6. SUBJECT IS ACR FUNCTIONAL CLASS I, II, OR III. (SEE APPENDIX 6.4)
7. SUBJECTS HAS RECEIVED MTX FOR A MINIMUM OF 3 MONTHS WITH A REGIONALLY APPROPIATE STABLE WEEKLY DOSE (15-25 MG/WK FOR REGIONS OUTSIDE OF ASIA 6-16 MG/WEEK FOR ASIA) FOR AT LEAST 4 WKS PRIOR TO ENTERING STUDY. DOSE OF WEEKLY METHOTREXATE MUST REMAIN STABLE THROUGH WEEK 24. THE INVESTIGATOR MUST ASSESS THE SUBJECT AS HAVING AN INADEQUATE RESPONSE TO MTX.

Exclusion criteria:
1. SUBJECT HAS INFLAMMATORY DISEASE OTHER THAN RA, INCLUDING BUT NOT LIMITED TO PSORIATIC ARTHRITIS, ANKYLOSING SPONDYLITIS, SYSTEMIC LUPUS ERYTHEMATOSUS, OR LYME DISEASE.
2. SUBJECT HAS SIGNS OR SYMPTOMS OF SEVERE, PROGRESSIVE, OR UNCONTROLLED RENAL, HEPATIC, HEMATOLOGIC, ENDOCRINE, PULMONARY, CARDIAC, NEUROLOGIC, OR CEREBRAL DISEASE, THAT AFFECTS THE SUBJECT´S ABILITY TO PARTICIPATE IN THE TRIAL.
3. SUBJECT HAS BEEN HOSPITALIZED DUE TO AN ACUTE CARDIOVASCULAR EVENT, CARDIOVASCULAR ILLNESS OR CARDIOVASCULAR SURGERY WITHIN 6 MONTHS OF SCREENING.
4. SUBJECT HAS SUSTAINED, UNCONTROILED HYPERTENSION (SYSTOLIC BLOOD PRESSURE OF ≥ 160 MM HG AND/OR DIASTOLIC BLOOD PRESSURE OF ≥ 100 MM HG AT BASELINE), OR UNCONTROLLED DIABETES.
5. SUBJECTS HAS A TRANSPLANTED ORGAN, EXCLUDING CORNEAL TRANSPLANT PERFORMED >3 MONTHS PRIOR TO FIRST DOSE OF TRIAL MEDICATION.
6. SUBJECT HAS HAD A PRIOR MALIGNANCY OR CONCURRENT MALIGNANCY (EXCLUDING SUCCESSFULLY TREATED BASAL CELL CARCINOMA, SQUAMOUS CELL CARCINOMA OF THE SKIN IN SITU, SQUAMOUS CELL CARCINOMA WITH NO EVIDENCE OF RECURRENCE WITHIN 5 YEARS, OR CARCINOMA IN SITU OF THE CERVIX THAT HAS BEEN ADEQUATELY TREATED).


Age minimum: 18
Age maximum: 75
Gender: --

Intervention(s)

THE FIRST THREE TREATMENT VISITS WILL OCCUR AT A ONE WEEK INTERVALS. VISIT 4 TO VISIT 6 WILL OCCUR AT A 2 WEEK INTERVALS AND EVERY 6 WEEKS THEREAFTER FOR A TOTAL OF 24 WEEKS.
GIVEN THE ADAPTIVE NATURE OF THE BASE STUDY, APPROXIMATELY 72 TO 434 MALE AND FEMALE SUBJECTS ≥ 18 YEARS OF AGE, WITH AT LEAST 3 MONTHS DIAGNOSIS OF ACTIVE RA MAY BE ENROLLED IN THE STUDY. SUBJECTS MUST HAVE BEEN TREATED WITH MTX FOR AT LEAST 3 MONTHS IMMEDIATELY PRIOR TO SCREENING. SUBJECTS WILL BE STRATIFIED BASED ON GEOGRAPHIC LOCATION AND CRP.
IN PHASE IIA/PERIOD 1, SUBJECTS WILL BE DOSED WITH MK-8457 100 MG BID + MTX OR PLACEBO + MTX FOR A TOTAL OF 24 WEEKS. SUBJECTS WILL ENROLL IN THE SAFETY EXTENSION (PERIOD 3) AT THE END OF PERIOD 1. AFTER APPROXIMATELY 58 SUBJECTS (29 SUBJECTS PER TREATMENT GROUP) HAVE COMPLETED 6 WEEKS OF TREATMENT IN PERIOD 1, AN INTERIM ANALYSIS (IA) WILL BE CONDUCTED TO EVALUATE FOR EFFICACY. EFFICACY IS DEFINED AS SUPERIORITY OF MK-8457 100 MG BID + MTX VERSUS PLACEBO ON CHANGE FROM BASELINE IN DAS28 SCORE.

Ethics review

Status: Approved
Approval date: 27/03/2012
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]

Status: Approved
Approval date: 13/09/2012
Contact:

[e-mail]

Instituto Regional de Oftalmologia - Trujillo

044-249066

[e-mail]

Status: Approved
Approval date: 26/09/2012
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]