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Regeneron has discontinued further clinical development of REGN5069, an antibody to GFRα3, which was previously being studied in osteoarthritis pain of the knee
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The primary objective of the study is to evaluate the efficacy of REGN5069 compared to placebo in patients with pain due to radiographically-confirmed OA of the knee who have a history of inadequate joint pain relief or intolerance to current analgesic therapy.
The secondary objectives of the study are:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| REGN5069 Low Dose | Experimental | Randomized in a 1:1:1 ratio |
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| REGN5069 High Dose | Experimental | Randomized in a 1:1:1 ratio |
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| Matching Placebo | Experimental | Randomized in a 1:1:1 ratio |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| REGN5069 | Drug | Intravenous (IV) Dose every 4 weeks (Q4W) |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12 in WOMAC Total Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Other protocol defined inclusion/exclusion criteria apply.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trial Management | Regeneron Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Regeneron Study Site | DeLand | Florida | 32720 | United States | ||
| Regeneron Study Site |
All IPD that underlie publicly available results will be considered for sharing
Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, EMA, PMDA, etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
A total of 259 participants were randomized in 1:1:1 ratio to receive REGN5069 at 100 mg IV Q4W, REGN5069 at 1000 mg IV Q4W, or matching placebo Q4W. Participants were to receive 3 fixed-dose IV infusions at baseline, week 4, and week 8. 171 participants were randomized to receive REGN5069 (86 participants in the 100 mg Q4W group and 85 in the 1000 mg Q4W group) and 88 were randomized to receive placebo.
The study was conducted in 5 countries and 12 sites participated in enrollment. It consisted of screening period up to 30 days, followed by a 12-week randomized, double-blind, placebo-controlled treatment period, a 24-week follow-up period, and end-of-study phone call approximately 52 weeks after first dose. Study was terminated after all participants completed the week 36 visits.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received matching placebo intravenously every 4 weeks (Q4W) |
| FG001 | REGN5069 100 mg Q4W | Participants received 100 milligrams (mg) of REGN5069 intravenously every 4 weeks (Q4W) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 4, 2019 | Apr 28, 2021 |
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| Matching Placebo | Drug | Intravenous (IV) Dose every 4 weeks (QW4) |
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| Week 12 |
| Change From Baseline to Week 12 in WOMAC Physical Function Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Week 12 |
| Change From Baseline to Week 12 in Patient Global Assessment (PGA) Score | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Week 12 |
| Change From Baseline to Week 12 in WOMAC Stiffness Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Week 12 |
| Percentage of Participants With ≥30% Improvement in WOMAC Pain Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Week 12 |
| Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | An adverse event (AE) is any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug. Treatment-emergent AEs (TEAEs) are AEs that developed or worsened during the treatment period. | Baseline to Week 36 |
| Number of Imaging Abnormalities Consistent With Adjudicated Arthropathies Through End of Study | Adjudicated arthropathy is an umbrella term referring to Rapidly Progressive Osteoarthritis Type 1 (RPOA-1), Rapidly Progressive Osteoarthritis Type 2 (RPOA-2), subchondral insufficiency fractures (SIF) and osteonecrosis (ON) confirmed by an arthropathy adjudication committee. | Baseline to Week 36 |
| Number of Participants With Presence of Anti-REGN5049 Antibody Development Through End of Study | Immunogenicity will be characterized by ADA responses & titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses < 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, ≥ 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the REG5069 ADA assay post first dose when baseline results = negative or missing. | Baseline to Week 36 |
| Jupiter |
| Florida |
| 33458 |
| United States |
| Regeneron Study Site | Miami | Florida | 33143 | United States |
| Regeneron Study Site | Charleston | South Carolina | 29406 | United States |
| Regeneron Study Site | Tbilisi | 112 | Georgia |
| Regeneron Study Site | Chisinau | MD2025 | Moldova |
| Regeneron Study Site | Lublin | Lublin Voivodeship | 20-412 | Poland |
| Regeneron Study Site | Zamość | Lublin Voivodeship | 22-400 | Poland |
| Regeneron Study Site | Warsaw | Masovian Voivodeship | 02 - 777 | Poland |
| Regeneron Study Site | Bialystok | Podlaskie Voivodeship | 15-879 | Poland |
| Regeneron Study Site | Zgierz | Łódź Voivodeship | 95-100 | Poland |
| Regeneron Study Site | Kyiv | 1135 | Ukraine |
| FG002 | REGN5069 1000 mg Q4W | Participants received 1000 milligrams (mg) of REGN5069 intravenously every 4 weeks (Q4W) |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received matching placebo intravenously every 4 weeks (Q4W) |
| BG001 | REGN5069 100 mg Q4W | Participants received 100 milligrams (mg) of REGN5069 intravenously every 4 weeks (Q4W) |
| BG002 | REGN5069 1000 mg Q4W | Participants received 1000 milligrams (mg) of REGN5069 intravenously every 4 weeks (Q4W) |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Full analysis set population (FAS): included all randomized participants | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Full analysis set population (FAS): included all randomized participants | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Full analysis set population (FAS): included all randomized participants | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Full analysis set population (FAS): included all randomized participants | Number | Participants |
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| Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Here 'n' = number of evaluable participants at this time interval | Mean | Standard Deviation | Scores on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Full analysis set population (FAS): included all randomized participants; Here 'n' = number of evaluable participants at the specific time point. | Posted | Least Squares Mean | Standard Error | Scores on a scale | Baseline to Week 12 |
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| Secondary | Change From Baseline to Week 12 in WOMAC Total Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Full analysis set population (FAS): included all randomized participants; Here "number analyzed" = number of evaluable participants at this time interval | Posted | Least Squares Mean | Standard Error | Scores on a scale | Week 12 |
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| Secondary | Change From Baseline to Week 12 in WOMAC Physical Function Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Full analysis set population (FAS): included all randomized participants; Here 'n' = number of evaluable participants at the specific time point. | Posted | Least Squares Mean | Standard Error | Scores on a scale | Week 12 |
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| Secondary | Change From Baseline to Week 12 in Patient Global Assessment (PGA) Score | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Full analysis set population (FAS): included all randomized participants; Here 'n' = number of evaluable participants at the specific time point. | Posted | Least Squares Mean | Standard Error | Scores on a scale | Week 12 |
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| Secondary | Change From Baseline to Week 12 in WOMAC Stiffness Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Full analysis set population (FAS): included all randomized participants; Here 'n' = number of evaluable participants at the specific time point. | Posted | Least Squares Mean | Standard Error | Scores on a scale | Week 12 |
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| Secondary | Percentage of Participants With ≥30% Improvement in WOMAC Pain Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Full analysis set population (FAS): included all randomized participants | Posted | Number | Percentage of participants | Week 12 |
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| Secondary | Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | An adverse event (AE) is any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug. Treatment-emergent AEs (TEAEs) are AEs that developed or worsened during the treatment period. | Safety Analysis Set (SAF): included all randomized participants who received any study drug | Posted | Number | Events | Baseline to Week 36 |
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| Secondary | Number of Imaging Abnormalities Consistent With Adjudicated Arthropathies Through End of Study | Adjudicated arthropathy is an umbrella term referring to Rapidly Progressive Osteoarthritis Type 1 (RPOA-1), Rapidly Progressive Osteoarthritis Type 2 (RPOA-2), subchondral insufficiency fractures (SIF) and osteonecrosis (ON) confirmed by an arthropathy adjudication committee. | Safety Analysis Set (SAF): included all randomized participants who received any study drug | Posted | Number | Events | Baseline to Week 36 |
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| Secondary | Number of Participants With Presence of Anti-REGN5049 Antibody Development Through End of Study | Immunogenicity will be characterized by ADA responses & titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses < 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, ≥ 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the REG5069 ADA assay post first dose when baseline results = negative or missing. | Anti-Drug Antibody (ADA) Analysis Set: included all treated participants who received any amount of study drug (active or placebo [safety analysis set (SAF)]) and had at least one non-missing anti-REGN5069 antibody result following the first dose of study drug or placebo. ADA analysis set is based on actual treatment received, rather than randomized. | Posted | Count of Participants | Participants | Baseline to Week 36 |
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Adverse events (AE) and Serious Adverse Events (SAE) were collected from the time of informed consent signature and then at each visit until the end of follow-up visit (week 36) for AEs and until end of study visit (week 52) for SAEs. The study was terminated early at 36 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received matching placebo intravenously every 4 weeks (Q4W) | 0 | 88 | 3 | 88 | 48 | 88 |
| EG001 | REGN5069 100 mg IV Q4W | Participants received 100 milligrams (mg) of REGN5069 intravenously every 4 weeks (Q4W) | 0 | 85 | 3 | 85 | 33 | 85 |
| EG002 | REGN5069 1000 mg IV Q4W | Participants received 1000 milligrams (mg) of REGN5069 intravenously every 4 weeks (Q4W) | 0 | 84 | 0 | 84 | 36 | 84 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Clostridium difficile colitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Meniscus injury | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
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| Ischaemic stroke | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
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| Transient ischaemic attack | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials Administrator | Regeneron Pharmaceuticals, Inc. | 844-734-6643 | clinicaltrials@regeneron.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 17, 2020 | Apr 28, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| D010146 | Pain |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Native Hawaiian or Other Pacific Islander |
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| Not reported |
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| Other |
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| Participants |
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| OG002 | REGN5069 1000 mg Q4W | Participants received 1000 milligrams (mg) of REGN5069 intravenously every 4 weeks (Q4W) |
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