Rheumatoid ArthritisPhase 3GEMENENCT03332719
Efficacy, Safety and Immunogenicity of Enerceptan Compared to Enbrel in Rheumatoid Arthritis
A Phase 3 study testing Etanercept and Methotrexate in people with Rheumatoid Arthritis, run by Gema Biotech S.A. at 1 site in Argentina.
Trial summary
The purpose of this study is to asses the compared efficacy, safety and immunogenicity of ENERCEPTAN® with ENBREL® in combination with Methotrexate for the treatment of patients with rheumatoid arthritis. Read more about this study
- Who is it for?
- Ages 19 to 99 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Etanercept and Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 1 siteArgentina
- Study dates
- Feb 2016to Sep 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult men and women over 18 years, who present moderate to severe active RA (rheumatoid arthritis) , diagnosed according to ACR/ EULAR 2010 criteria, who have failed prior MTX (methotrexate) therapy. Functional class I to III.
- Moderate to severe disease activity, according to DAS28 (erythrosedimentation) ≥ 3.2.
- Must have at least a minimum of 6 tender joints and 8 swollen joints. If a patient has a joint surgery prior to the study, this joint is considered not evaluable throughout the study development.
- Must have at least, one erosion in the baseline radiograph. Local assessment centers either radiologist or rheumatologist to decide on this criterion will be accepted.
- Medical Indication to incorporate a biological treatment in their therapy.
- Treatment with MTX for at least 3 months on dose ≥15 mg/ week, stable over the last 28 days before the Day 1. Doses lower than 15 mg and greater or equal than 10 mg/ week are accepted in cases with previously documented intolerance.
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- Subjects who have previously received treatment with a biologic (approved or investigational) except etanercept, may participate as long as the corresponding washout time has elapsed prior to the screening interview: At least
- 8 weeks for infliximab (T1/2 8 to 9.5 days) and for tocilizumab (T1/2 3to 12 days)
- 10 weeks for adalimumab (T1/2 10 to 20 days), Golimumab (T1/2 11 to 14 days), certolizumab (T1/2 14 days), abatacept (T1/2 14 days),
- 1 year for Rituximab (T1/2 77,5 days)
- 5 T1/2 for any other biological product, used for the treatment of rheumatoid arthritis, wether it has been used or not for research.
- Subjects who are receiving leflunomide must have a previous washout of 8 weeks before Day 1, except had have treatment with colestyramine, according to manufacturer indications.
- Can receive non steroidal anti inflammatory drugs (NSAIDs) or oral corticoids in doses < 10 mg of prednisone, but treatment must have been stable over the last 28 days.
- 8 Subjects must be able to self-inject or willing to have a previously assigned caregiver do it for them.
- 9 Subjects must be able to meet the schedule of visits, understand and comply with other protocol requirements.
- 10 Women of childbearing age must commit to be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of Enbrel®/Enerceptan®. Suitable methods of contraception are oral contraceptives, IUDs (intrauterine device) , bilateral tubal ligation, vasectomy or double barrier methods such as condoms or spermicidal diaphragm, sponge, contraceptive foam or gel, heterosexual abstinence. Men should not conceive up to 12 weeks after stopping the MTX
- 11 Informed consent must be signed before making any study-specific procedure.
Who cannot join
- Simultaneous treatment with other investigational drug or participation in another clinical study that the investigator considers inadvisable.
- Women who are pregnant or breastfeeding.
- Past history of nonresponsive to TNF (tumor necrosis factor) blocking agents or other biologic treatment.
- Chronic antibiotic therapy, if the investigator considers this may affect the safety of the subject or the assessment of the study results.
- Any previous or current serious medical conditions that, in the opinion of the investigator, constitute a contraindication for the study treatment, as:
- Administration of vaccines:
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- Subjects who have received a live attenuated vaccine within 3 months prior to the randomization Visit (for example, varicella-zoster, oral polio, rabies, yellow fever vaccines.)
- Subjects who have received the BCG (bacillus Calmette-Guerin) vaccine within 12 months before the Selection.
- Presence of :
- At the time of the inclusion i. Active infections. ii. Fever (≥38 °C) or active, chronic or recurrent infections that require treatment with antibiotics, antiviral, or anti-fungal medications within 4 weeks prior to Screening Visit, or history of frequent recurrent infections unacceptable to the investigator's opinion.
- Non-healing infected skin ulcers. b. In the previous time: i. Background of recurrent bacterial, viral, fungal (excluding superficial infections or nail bed mycosis), mycobacterial or other severe infections within the last month previous to selection.
- Hospitalization for infection or Subjects who have received antibiotics intravenously within the last month or orally within the last 2 weeks.
- Subjects with herpes zoster in the last 2 months.
- Past history of drug or alcohol abuse within the last year prior to the Screening Visit.
- Known hypersensitivity to the study drug or history of severe allergy or anaphylactic reaction to monoclonal antibodies or fusion or human proteins.
- Any condition that, in the investigator opinion, would not allow compliance with the guidelines of the study by the patient.
- The subject presents absolute contraindications for the use of etanercept, according to the prospectus
- Presence of significant laboratory abnormalities in the screening visit.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multicentric Evaluator-blinded Randomized Non-inferiority Study, to Asses the Compared Efficacy, Safety and Immunogenicity of Enerceptan® With Enbrel® in Combination With Methotrexate for the Treatment of Patients With Rheumatoid Arthritis
The purpose of this study is to asses the compared efficacy, safety and immunogenicity of ENERCEPTAN® with ENBREL® in combination with Methotrexate for the treatment of patients with rheumatoid arthritis.
Read the detailed description
Randomized, , non-inferiority, two parallel arms, 32 weeks, blind for the assessor.
Subjects should be with inadequate response to methotrexate with stable dosis ≥ 15 and ≤ 25 mg/week 28 days before randomization.
Randomization will be 2:1 Enerceptan® to Enbrel® with concomitant medication of MTX
- Conditions
- Rheumatoid Arthritis
- Being tested
- Etanercept, Methotrexate
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptBiological
MethotrexateDrug
| Study group | Role | What they receive |
|---|---|---|
| Enbrel® | Active comparator | Enbrel® 50 mg injectable solution in autoinjector SureClick® contains: 50 mg etanercept and excipients/Once a week Methotrexate 15 to 25 mg /Once a week Receives: Biological: Etanercept; Drug: Methotrexate |
| Enerceptan®. | Experimental | Enerceptan®. Injectable Solution in prefilled syringes Source: GEMABIOTECH S. A. Formulation per unit: 1,0 ml of Enerceptan® contains 50 mg solution of Etanercept /Once a week Methotrexate 15 to 25 mg /Once a week Receives: Biological: Etanercept; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
ACR (American College of Rheumatology) 20
The percentage of patients who achieved ACR20 at Week 32 is the primary end point. Signs and symptoms are assessed with a composite rating scale of the ACR (American College of
Rheumatology) that includes 7 variables:
- Tender Joints Count
- Swollen Joints Count
- Levels of an acute phase reactant (CRP level)
- Patient's assessment of pain
- Patient's global assessment of disease activity
- Physician's global assessment of disease activity
- Patient's assessment of physical function
Measured: 32 weeks of treatment
Secondary outcomes (11)
ACR (American College of Rheumatology) 50
ACR50 is defined as the percentage of patients who achieve at least 50% improvement in both tender joint count and swollen joint count, and at least 50% improvement in at least 3 of the 5 other assessments.
Measured: 32 weeks of treatment
ACR (American College of Rheumatology) 70
ACR70 is defined as the percentage of patients who achieve at least 70% improvement in both tender joint counts and swollen joint counts and at least 70% improvement in at least 3 of the 5 other assessments of the ACR
Measured: 32 weeks of treatment
DAS (Disease activity state)
It will be measured using the DAS (Disease activity state) 28. DAS28 is a composite score that includes 4 variables:
- Tender Joints Count (based on 28 joints)
- Swollen Joints Count (based on 28 joints)
- Patient's global assessment of disease activity
- Marker of inflammation: C REACTIVE PROTEIN
Measured: 32 weeks of treatment
EULAR (European League Against Rheumatism) response criteria
- Good response = Percentage of patients with an improvement of >1.2 and a present DAS score ≤3.2.
- Moderate response = Percentage of patients with either an improvement of >0.6 to ≤1.2 and a present score ≤5.1, or an improvement >1.2 and a present score >3.2
- Non response = Percentage of patients with either an improvement of ≤0.6 or an improvement >0.6 to ≤1.2 and a present score >5.1
Measured: 32 weeks of treatment
Time to onset of benefit
ACR20, will be also analyzed at every clinic visit to allow an analysis of the time to onset of benefit for achievement of ACR
Measured: 32 weeks of treatment
Change in modified van der Heijde Sharp score
- The Sharp method is a composite X-ray scoring system used to assess structural (joint) disease progression in rheumatoid arthritis. The method evaluates both joint erosions (JE) and joint space narrowing (JSN) in bilateral hand and foot joints
Measured: 32 weeks of treatment
Physical function
- Improvement in physical function is assessed by change from baseline in HAQ (Health Assessment Questionnaire) at Week 32.The HAQ-DI (disability index) is composed of 8 categories as follows: dressing and grooming, arising, eating, walking, hygiene, reach, grip and activities, for which there are at least 2 questions by category. The patient will be asked to score how difficult he/she feels it is to perform such activities using a 0 to 3 scoring (0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do). If the patient is using assistance for any of these activities, scoring may be adjusted. For each category, the highest score given for one of the question is attributed to the category. The total score is the sum of all categories' scores divided by the number of answered categories (at least 3 categories should be answered)
Measured: 32 weeks of treatment
Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-Fatigue)
The FACIT-Fatigue is a 13-item questionnaire rated 0 to 4. The patient will be asked to answer to 13 questions rated 0 to 4 (0=not at all,
1=a little bit, 2=some what, 3=quite a bit, 4=very much
Measured: 32 weeks of treatment
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
Infections, hematological disorders, neurologic disorders and malignancies. Adverse Drug Reactions. Incidence, seriousness and severity. Serum Hematological and chemistry values.Local Adverse Drug Reactions
Measured: 32 weeks of treatment
Steady state concentration
Etanercept concentration measure
Measured: At week 16 and 32
Immunogenicity
Antibodies anti-Etanercept measure
Measured: At week 16 and 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study startFeb 2016
- Primary completionMar 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gema Biotech S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- QUID Quality in Drugs and Devices Latin American Consulting SRL
- Responsible party
- Sponsor
- Investigators
- Jorge Velasco, MD, Principal investigator, Instituto Médico CERMaria de los Angeles Correa, MD, Principal investigator, PAMPAMaria Alicia Lazaro, MD, Principal investigator, IARIRodolfo Pardo Hidalgo, MD, Principal investigator, CER San JuanDaniel Siri, MD, Principal investigator, CAICIAlberto Jorge Spindler, MD, Principal investigator, Centro Médico Privado de ReumatologíaIngrid Strusberg, MD, Principal investigator, Centro Reumatologico StrusbergPatricio Tate, MD, Principal investigator, OMI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03332719
- Sponsor's protocol ID
- GEMENE001
- Acronym
- GEMENE
- Status last verified
- Oct 2017
- First submitted
- 21 Apr 2016
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Strusberg I, Mysler E, Citera G, Siri D, de Los Angeles Correa M, Lazaro MA, Pardo Hidalgo R, Spindler A, Tate P, Venarotti H, Velasco Zamora J, Klimovsky E, Federico A, Scheines E, Gonzalez E, Cordeiro L, Lago N. Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis: A Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study. J Clin Rheumatol. 2021 Sep 1;27(6S):S173-S179. doi: 10.1097/RHU.0000000000001616.
PubMed 33337815
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentric Evaluator-blinded Randomized Non-inferiority Study, to Asses the Compared Efficacy, Safety and Immunogenicity of Enerceptan® With Enbrel® in Combination With Methotrexate for the Treatment of Patients With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03332719
- Acronym / sponsor ID
- GEMENE / GEMENE001
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- Gema Biotech S.A.Industry (pharma, biotech, devices)
- Collaborators
- QUID Quality in Drugs and Devices Latin American Consulting SRL
- Study start
- Feb 2016
- Primary completion
- Mar 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to asses the compared efficacy, safety and immunogenicity of ENERCEPTAN® with ENBREL® in combination with Methotrexate for the treatment of patients with rheumatoid arthritis.
Detailed description
Randomized, , non-inferiority, two parallel arms, 32 weeks, blind for the assessor.
Subjects should be with inadequate response to methotrexate with stable dosis ≥ 15 and ≤ 25 mg/week 28 days before randomization.
Randomization will be 2:1 Enerceptan® to Enbrel® with concomitant medication of MTX
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enbrel® | Active comparator | Biological: Etanercept, Drug: MethotrexateEnbrel® 50 mg injectable solution in autoinjector SureClick® contains: 50 mg etanercept and excipients/Once a week Methotrexate 15 to 25 mg /Once a week |
| Enerceptan®. | Experimental | Biological: Etanercept, Drug: MethotrexateEnerceptan®. Injectable Solution in prefilled syringes Source: GEMABIOTECH S. A. Formulation per unit: 1,0 ml of Enerceptan® contains 50 mg solution of Etanercept /Once a week Methotrexate 15 to 25 mg /Once a week |
Who may qualify
- Ages
- 19 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Adult men and women over 18 years, who present moderate to severe active RA (rheumatoid arthritis) , diagnosed according to ACR/ EULAR 2010 criteria, who have failed prior MTX (methotrexate) therapy. Functional class I to III.
- Moderate to severe disease activity, according to DAS28 (erythrosedimentation) ≥ 3.2.
- Must have at least a minimum of 6 tender joints and 8 swollen joints. If a patient has a joint surgery prior to the study, this joint is considered not evaluable throughout the study development.
- Must have at least, one erosion in the baseline radiograph. Local assessment centers either radiologist or rheumatologist to decide on this criterion will be accepted.
- Medical Indication to incorporate a biological treatment in their therapy.
Key exclusion criteria (18 listed)
- Simultaneous treatment with other investigational drug or participation in another clinical study that the investigator considers inadvisable.
- Women who are pregnant or breastfeeding.
- Past history of nonresponsive to TNF (tumor necrosis factor) blocking agents or other biologic treatment.
- Chronic antibiotic therapy, if the investigator considers this may affect the safety of the subject or the assessment of the study results.
- Any previous or current serious medical conditions that, in the opinion of the investigator, constitute a contraindication for the study treatment, as:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Etanercept | Biological | Enbrel®, Enerceptan®. |
| Methotrexate | Drug | Enbrel®, Enerceptan®. |
Primary outcome
ACR (American College of Rheumatology) 20
Time frame: 32 weeks of treatment
The percentage of patients who achieved ACR20 at Week 32 is the primary end point. Signs and symptoms are assessed with a composite rating scale of the ACR (American College of Rheumatology) that includes 7 variables: * Tender Joints Count * Swollen Joints Count * Levels of an acute phase reactant (CRP level) * Patient's assessment of pain * Patient's global assessment of disease activity * Physician's global assessment of disease activity * Patient's assessment of physical function
11 secondary outcomes
ACR (American College of Rheumatology) 50
Time frame: 32 weeks of treatment
ACR (American College of Rheumatology) 70
Time frame: 32 weeks of treatment
DAS (Disease activity state)
Time frame: 32 weeks of treatment
EULAR (European League Against Rheumatism) response criteria
Time frame: 32 weeks of treatment
Time to onset of benefit
Time frame: 32 weeks of treatment
Change in modified van der Heijde Sharp score
Time frame: 32 weeks of treatment
Physical function
Time frame: 32 weeks of treatment
Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-Fatigue)
Time frame: 32 weeks of treatment
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
Time frame: 32 weeks of treatment
Steady state concentration
Time frame: At week 16 and 32
Immunogenicity
Time frame: At week 16 and 32
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
- Derived from this study: PubMed 33337815Strusberg I, Mysler E, Citera G, Siri D, de Los Angeles Correa M, Lazaro MA, Pardo Hidalgo R, Spindler A, Tate P, Venarotti H, Velasco Zamora J, Klimovsky E, Federico A, Scheines E, Gonzalez E, Cordeiro L, Lago N. Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis: A Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study. J Clin Rheumatol. 2021 Sep 1;27(6S):S173-S179. doi: 10.1097/RHU.0000000000001616.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge Velasco, MD principal investigator
Instituto Médico CER
Maria de los Angeles Correa, MD principal investigator
PAMPA
Maria Alicia Lazaro, MD principal investigator
IARI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Etanercept and Methotrexate in people with Rheumatoid Arthritis, run by Gema Biotech S.A. at 1 site in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ACR (American College of Rheumatology) 20 (time frame: 32 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03332719, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.