TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600, AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04413617
• Collaborator: (none)
• Enrollment: 460
• Locations: 144
• Arms: 5
• Actual Duration (Months): 18.3
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Dual objectives of increased efficacy compared to currently available SoC RA drugs and maintaining a favourable benefit - risk relationship.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: PF-06650833; Drug: PF-06651600; Drug: Tofacitinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 460 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 24-WEEK RANDOMIZED, DOUBLE-BLIND, PARALLEL GROUP, ACTIVE COMPARATOR, MULTICENTER STUDY TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600 (RITLECITINIB) AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH MODERATELY-SEVERELY ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
• Actual Study Start Date: Jul 29, 2020
• Actual Primary Completion Date: Feb 7, 2022
• Actual Study Completion Date: Feb 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-06650833 + tofacitinib	Drug: PF-06650833; 400 mg; Drug: Tofacitinib; 11 mg
Experimental: PF-06650833 + PF-06651600	Drug: PF-06650833; 400 mg; Drug: PF-06651600; 100 mg
Experimental: PF-06650833	Drug: PF-06650833; 400 mg
Experimental: PF-06651600	Drug: PF-06651600; 100 mg
Experimental: Tofacitinib	Drug: Tofacitinib; 11 mg

Outcome Measures

Primary Outcome Measures

1. Change from baseline in Disease Activity Score (DAS)28-C Reactive protein (CRP) [Week 12]

Secondary Outcome Measures

1. DAS28-CRP remission (<2.6) [Week 24]

2. Change from baseline in Disease Activity Score (DAS)28-C Reactive protein (CRP) [Week 24]

3. American College of Rheumatology (ACR)20, ACR 50, ACR 70, and ACR 90 responder rates [Weeks 12 and 24]

4. Change from baseline in the Tender/Painful and Swollen Joint Count [Weeks 12 and 24]

5. Change from baseline in the Physician's Global Assessment (PhGA) of Arthritis [Weeks 12 and 24]

6. Incidence and severity of adverse events, serious adverse events, and withdrawals due to adverse events. [Baseline through Week 28]

7. Incidence of abnormality in clinical chemistry parameters [Baseline through Week 28]

8. Incidence of abnormality in hematological parameters [Baseline through Week 28]

9. Change from baseline in blood pressure measurement [Baseline through Week 28]

10. Change from baseline in pulse rate measurement [Baseline through Week 28]

11. Change from baseline in temperature measurement [Baseline through Week 28]

12. Incidences of targeted medical adverse events [Baseline through Week 28]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female participants between the ages of 18 and 70 years.

• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

• Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/10.

• The participant has active disease at both Screening and Randomization, as defined by both: ≥6 joints tender or painful on motion, AND ≥6 joints swollen; and fulfills 1 of the following 2 criteria: High sensitivity C reactive protein (hsCRP) >7 mg/L at Screening (Visit 1) as performed by the central laboratory OR Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm h.

Exclusion Criteria:

• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

• Participants with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.

• Participants with any active or latent infections.

• Participants with positive hepatitis B surface antigen (HBsAg).

• Participants with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA).

• Any history of either untreated or inadequately treated latent or active tuberculosis (TB) infection, current treatment for active or latent TB infection or evidence of currently active TB,

• History of a major organ transplant (eg, heart, lung, kidney and liver) or hematopoietic stem cell/marrow transplant.

• History of severe allergic or anaphylactoid reaction to kinase inhibitors, or corticosteroid preparations.

• Known history of diverticulitis or symptomatic diverticulosis, perineal abscess or fistulae.

• Participants with malignancy or history of malignancy (including lymphoma, leukemia, or lymphoproliferative disease).

• Pre-existing chronic autoimmune disease (eg, inflammatory bowel disease, systemic lupus erythematosus, moderate-severe atopic dermatitis, dermatomyositis) other than RA. Secondary Sjogren's Syndrome (due to RA) may be included.

• Participants with fibromyalgia will be excluded.

• Previous treatment with total lymphoid irradiation.

• Participants with an oral, tympanic, or temporal temperature of 38°C (100.4°F) or higher at baseline.

• Participants may not receive any live/attenuated vaccine from 30 days prior to randomization during the course of the study, or for 30 days after the last dose of study medication. Participants who have current routine household contact with children who have received varicella or oral polio vaccine within 2 months of first study dose are also excluded.

• History of any lymphoproliferative disorder.

• Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease.

• History of any prior deep vein thrombosis (DVT) or pulmonary embolism [PE].

• Recent (within 6 months of screening) myocardial infarction, coronary revascularization, or percutaneous angioplasty with or without placement of a coronary artery stent; acute coronary syndrome; chronic uncompensated heart failure or New York Heart Association Functional Class III or IV; left ventricular assist devices; implanted defibrillators.

• Current severe chronic renal insufficiency or renal failure as defined by persistent (on repeated measurements) eGFR <60 mL/min per 1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation.

• Any known coagulopathy or hypercoagulant syndrome.

• Presence of any of the following laboratory abnormalities at screening or within the 3 months prior to first study dose:

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥1.5 x the upper limit of normal (ULN); Participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN and other liver function assessments are normal; Absolute neutrophil count of <1.5 x 109/L (<1500/mm3). Participants with cyclic (benign ethnic) neutropenia will be excluded; Absolute lymphocyte count of <0.5 x 109/L (<500/mm3); Absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3); Hemoglobin <9.0 g/dL (90 g/L); Platelet count ≤100 x 109/L (100,000 cells/mm3) or ≥1000 x 109/L (1,000,000 cells/mm3); Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3) at screening visit or within the 3 months prior to first study dose. [Screening laboratory tests with abnormal results may be repeated once to confirm abnormal results. If results return to normal protocol acceptable limits within the 4-week screening period, the participant may enter the study].

• Grade 3 or greater laboratory abnormality based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity scale, except for the following that are allowed: Grade 3 prothrombin time (PT) secondary to warfarin treatment; Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy.

• Participants previously treated with a biologic DMARD (except for up to 25% of participants who may have been treated with 1, and only 1 prior TNF inhibitor) or any other recent DMARD treatment (eg, a JAK inhibitor), or participants currently treated with any other prohibited medications will be excluded.

• Prior use of tofacitinib or other JAK inhibitor in the context of a clinical trial is excluded. Concomitant use of tofacitinib (other than as prescribed by the randomization scheme) or other JAK inhibitor is prohibited.

• Participants who have previously been treated with other, non-TNFa inhibiting biologic DMARDs [including, abatacept (Orencia®), tocilizumab (Actemra®), Sarilumab (Kevzara®), anakinra (Kineret®), rituximab (Rituxan®) or other selective B lymphocyte depleting agents, or other lymphocyte depleting agents/therapies (such as alemtuzab [CamPath®], natalizumab (Tysabri®), alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation) are excluded from participation in the study.

• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of IP used in this study (whichever is longer).

• Any 12-lead electrocardiogram (ECG) performed prior to randomization that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	,,UMHAT - Georgi Stranski" EAD	Pleven		Bulgaria	5800
2	Medical Diagnostic Laboratory Rusev EOOD	Plovdiv		Bulgaria	4000
3	MHAT Plovdiv AD	Plovdiv		Bulgaria	4000
4	DCC Sveti Georgi EOOD	Plovdiv		Bulgaria	4002
5	Independent Medical Diagnostic Laboratory Mediscan EOOD	Plovdiv		Bulgaria
6	"Medical Center-Teodora" EOOD	Ruse		Bulgaria	7002
7	UMHAT "Kanev" AD	Ruse		Bulgaria	7002
8	Medical Center "Spectar" OOD	Sofia		Bulgaria	1113
9	MHAT "Lyulin" EAD	Sofia		Bulgaria	1336
10	"DCC 17 - Sofia" EOOD	Sofia		Bulgaria	1505
11	Medical Center "N.I. Pirogov" EOOD	Sofia		Bulgaria	1612
12	UMHAT "Sveti Ivan Rilski" EAD	Sofia		Bulgaria	1612
13	Manitoba Clinic	Winnipeg	Manitoba	Canada	R3A 1M3
14	Centre de Rhumatologie de l'Est du Quebec (CREQ)	Rimouski	Quebec	Canada	G5L 8W1
15	Centro Radiologico San Vicente de Paul	Santiago	Region Metropolitana	Chile	7500509
16	CTR Estudios	Santiago	Region Metropolitana	Chile	7500571
17	Enroll SpA	Santiago	Region Metropolitana	Chile	7500587
18	Centro Radiologico Plaza Baquedano	Santiago	Region Metropolitana	Chile	7500906
19	IMARED	Santiago	Region Metropolitana	Chile	7501070
20	Centro de Estudios Reumatologicos (CER)	Santiago	Region Metropolitana	Chile	7501126
21	CCR Czech a.s.	Pardubice	Vychodocesky KRAJ	Czechia	53002
22	REVMACLINIC s.r.o.	Brno		Czechia	61141
23	Revmacentrum MUDr. Mostera, s.r.o.	Brno		Czechia	615 00
24	HV Medical s.r.o., ORL ambulance pro deti a dospele	Brno		Czechia	635 00
25	MRI Lekarsky servis s.r.o.	Havirov		Czechia	736 01
26	Poliklinika AMO - Audiologie	Ostrava - Kuncice		Czechia	70702
27	CCR Ostrava, s.r.o.	Ostrava		Czechia	702 00
28	Vesalion s.r.o.	Ostrava		Czechia	702 00
29	Mestka nemocnice Ostrava	Ostrava		Czechia	728 80
30	ORL - sluchadla s.r.o.	Pardubice		Czechia	530 02
31	Poliklinika Vektor	Pardubice		Czechia	530 02
32	Revmatologicky ustav	Praha 2		Czechia	128 50
33	Thomayerova nemocnice	Praha 4		Czechia	140 59
34	ORL ambulance	Uherske Hradiste		Czechia	686 01
35	Uherskohradistska nemocnice, a.s.	Uherske Hradiste		Czechia	686 68
36	Medical Plus s.r.o.	Uherske Hradiste		Czechia	68601
37	JSC "Evex Hospitals"	Tbilisi		Georgia	0159
38	LTD "Cardioclinic - Digomi Medical Center"	Tbilisi		Georgia	0159
39	LTD "Institute of Clinical Cardiology"	Tbilisi		Georgia	0159
40	LTD "MediClub Georgia"	Tbilisi		Georgia	0160
41	LTD "Multi-Profile Clinic Consilium Medulla"	Tbilisi		Georgia	0186
42	Trial Pharma Kft.	Bekescsaba		Hungary	5600
43	Vasutegeszsegugyi Nonprofit Kozhasznu Tarsasag	Bekescsaba		Hungary	5600
44	Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz	Budapest		Hungary	1023
45	Mammut Egeszsegkozpont, Ful-orr- gegeszet	Budapest		Hungary	1024
46	Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz	Budapest		Hungary	1027
47	Budai Irgalmasrendi Korhaz	Budapest		Hungary	1027
48	Revita Reumatologiai Rendelo	Budapest		Hungary	1027
49	Qualiclinic Kft.	Budapest		Hungary	1036
50	Affidea Magyarorszag Kft.	Budapest		Hungary	1054
51	Affidea Magyarország Kft. Bank Center Központ	Budapest		Hungary	1054
52	Magyar Honvédség Egészségügyi Központ	Budapest		Hungary	1062
53	Affidea Magyarorszag Kft. Vaci Greens Egeszsegkozpont	Budapest		Hungary	1138
54	Mediszintech Audiologia Kft.	Budapest		Hungary	1148
55	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
56	Debreceni Egyetem Klinikai Központ	Debrecen		Hungary	4032
57	Sanitas Diagnosztikai es Rehabilitacios Kozpont	Gyula		Hungary	5700
58	Pest Megyei Flór Ferenc Kórház Fül- Orr- Gégészet és Gyermek Fül-Orr-Gégészet	Kistarcsa		Hungary	2143
59	Pest Megyei Flór Ferenc Kórház Reumatológiai es Fizioterápiás Osztály	Kistarcsa		Hungary	2143
60	Huniko Kereskedelmi és Egészségügyi Szolgáltató Kft.	Miskolc		Hungary	3530
61	Szegedi Tudomanyegyetem Reumatologiai Klinika	Szeged		Hungary	6725
62	Szegedi Tudomanyegyetem	Szeged		Hungary	6725
63	Szent-Gyorgyi Albert Klinikai Kozpont	Szeged		Hungary	6725
64	Csolnoky Ferenc Korhaz, Ful- Orr- Gegeszeti Osztaly	Veszprem		Hungary	8200
65	VITAL MEDICAL CENTER (VITÁL-MEDICINA Kft.)	Veszprém		Hungary	8200
66	Podlaskie Centrum Sluchu i Mowy Sluchmed	Bialystok		Poland	15-222
67	Nzoz Zdrowie Osteo-Medic	Bialystok		Poland	15-351
68	Lar-Med	Bialystok		Poland	15-369
69	NZOZ Kendron	Bialystok		Poland	15-402
70	Tomma Diagnostyka obrazowa	Bialystok		Poland	15-471
71	ClinicMed Daniluk, Nowak Sp. J.	Bialystok		Poland	15-879
72	Nzoz McD Voxel	Bydgoszcz		Poland	85-015
73	Klinika Foniatrii i Audiologii, Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy	Bydgoszcz		Poland	85-168
74	Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej	Bydgoszcz		Poland	85-168
75	Centrum Medyczne Pratia Gdynia	Gdynia		Poland	81-338
76	Portowy Zaklad Opieki Zdrowotnej Sp. z o.o.	Gdynia		Poland	81-338
77	Centrum Medyczne Enel-Med., Oddzial Alfa Plaza - Gdynia	Gdynia		Poland	81-366
78	MCBK	Grodzisk Mazowiecki		Poland	05-825
79	Samodzielny Publiczny Specjalistyczny Szpital Zachodni im. sw. Jana Pawla II	Grodzisk Mazowiecki		Poland	05-825
80	Malopolskie Badania Kliniczne	Krakow		Poland	30-002
81	LUX MED.	Krakow		Poland	30-004
82	Centrum Badan Klinicznych JCI	Krakow		Poland	30-348
83	Centrum medyczne PLEJADY	Krakow		Poland	30-363
84	LUXMED	Krakow		Poland	30-421
85	Pratia MCM Krakow	Krakow		Poland	30-510
86	Centrum Medycyny Profilaktycznej Sp. z o. o.	Krakow		Poland	31-513
87	Centrum Medyczne iMed24	Krakow		Poland	31-864
88	FONMED	Nowa Sol		Poland	67-100
89	Twoja Przychodnia - Centrum Medyczne Nowa Sol	Nowa Sol		Poland	67-100
90	LIVMED Sp. z.o.o.	Nowy Tomysl		Poland	64-300
91	Ai Centrum Medyczne	Poznan		Poland	61-113
92	Tomma Diagnostyka Obrazowa S.A.	Poznan		Poland	61-361
93	GEERS Dobry Sluch	Poznan		Poland	61-397
94	Prywatna Praktyka Lekarska Prof. dr hab. med. Pawel Hrycaj	Poznan		Poland	61-397
95	Pracownia Rezonansu Magnetycznego i RTG	Poznan		Poland	61-545
96	Centrum Mowy i Sluchu Medincus	Warszawa		Poland	00-024
97	Rex Medica Sport	Warszawa		Poland	00-838
98	Medycyna Kliniczna	Warszawa		Poland	00-874
99	Tomma Diagnostyka Obrazowa	Warszawa		Poland	01-201
100	"MTZ CLINICAL RESEARCH" Spolka z ograniczona odpowiedzialnoscia	Warszawa		Poland	02-106
101	"Reumatika - Centrum Reumatologii" NZOZ	Warszawa		Poland	02-691
102	ArtAna Anna Piotrowska	Warszawa		Poland	02-691
103	Spoldzielnia Pracy Specjalistow Rentgenologow im. prof. W. Zawadowskiego	Warszawa		Poland	02-796
104	Szpital LUX MED	Warszawa		Poland	02-801
105	Dermatovenerologicka ambulancia	Bratislava		Slovakia	83103
106	ROMJAN, s.r.o.	Bratislava		Slovakia	85101
107	ORL ambulancia RHINO s.r.o.	Bratislava		Slovakia	85104
108	Klinika dermatovenerologie UNLP	Kosice		Slovakia	040 11
109	ARTROMAC n. o.	Kosice		Slovakia	04011
110	Oddelenie radiodiagnostiky a zobrazovacich metod, UNLP	Kosice		Slovakia	04011
111	Poliklinika Terasa s.r.o.	Kosice		Slovakia	04011
112	Dermabene, s.r.o	Martin		Slovakia	03601
113	MEDMAN, s. r. o.,	Martin		Slovakia	03601
114	ORL ML, s.r.o	Martin		Slovakia	03601
115	Jessenius - Diagnosticke centrum	Nitra		Slovakia	949 01
116	Otorinolaryngologicka ambulancia MUDr. Olga Salgova	Partizanske		Slovakia	95801
117	PARDERM, s. r. o., Dermatovenerologicka ambulancia	Partizanske		Slovakia	95801
118	REUMACENTRUM s.r.o.	Partizanske		Slovakia	95801
119	MEDICENTRUM Piestany, s.r.o.	Piestany		Slovakia	92101
120	Narodny ustav reumatickych chorob	Piestany		Slovakia	92112
121	Nemocnica Alexandra Wintera n.o.	Piestany		Slovakia	92163
122	Vseobecna nemocnica Rimavska Sobota	Rimavska Sobota		Slovakia	979 12
123	AZIMED-ORL s.r.o.	Rimavska Sobota		Slovakia	97901
124	Dg.s.r.o. - Diagnosticke- centrum	Rimavska Sobota		Slovakia	97901
125	REUMEX s.r.o.	Rimavska Sobota		Slovakia	97901
126	Spinn, s.r.o.	Ruzomberok		Slovakia	034 01
127	Zdravomak s.r.o. Topoľčany	Topolcany		Slovakia	95501
128	Clinica Gaias - Santiago	Santiago de Compostela	A Coruna	Spain	15702
129	Grupo Hospitalario La Rosaleda - Hospital Nuestra Senora de la Esperanza	Santiago de Compostela	A Coruna	Spain	15705
130	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
131	Clinica Sagrada Familia	Barcelona		Spain	08022
132	Hospital Clinico Universitario Santiago de Compostela	Santiago de Compostela		Spain	15706
133	Hospital Quironsalud Infanta Luisa	Sevilla		Spain	41010
134	Communal non-profit enterprise "Chernihiv Regional Hospital" of Chernihiv Regional Council	Chernihiv		Ukraine	14029
135	Communal Non-commercial Enterprise of Kharkiv Regional Council	Kharkiv		Ukraine	61058
136	Medical сепtег of "Medical Clinic "Blagomed" LLC	Kyiv		Ukraine	01023
137	Medical Center 'Ok!Clinic+' of International Institute of Clinical Research LLC	Kyiv		Ukraine	02091
138	Communal non-profit enterprise "Kyiv City Clinical Hospital #3" of executive body of Kyiv	Kyiv		Ukraine	02125
139	Limited Liability Company "Medical Centre "Consilium Medical"	Kyiv		Ukraine	04050
140	"Revmocenter" LLC	Kyiv		Ukraine	04071
141	Clinic of the State Institution "DF Chebotaryov Institute of Gerontology of the NAMS of Ukraine"	Kyiv		Ukraine	04114
142	Communal Non-Commercial Enterprise "Odesa Regional Clinical Hospital" of Odesa Regional Council	Odesa		Ukraine	65025
143	Comunal Enterprise "Poltava Regional Clinical Hospital n. a. M.S. Sklifosovskogo of Poltava	Poltava		Ukraine	360011
144	LLC "Modern Clinic"	Zaporizhzhya		Ukraine	69005

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04413617
• Other Study ID Numbers: B7921023; 2019-002676-14
• First Posted: Jun 4, 2020
• Last Update Posted: Mar 4, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Pfizer: Rheumatoid Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Tofacitinib

Study Results

No Results Posted as of Mar 4, 2022