Osteoarthritis of the KneePhase 2NCT03956550
A Study to Examine the Efficacy and Safety of REGN5069 in Patients With Pain Due to Osteoarthritis of the Knee
A Phase 2 study testing REGN5069 in people with Osteoarthritis of the Knee and Pain, run by Regeneron Pharmaceuticals at 12 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Osteoarthritis of the Knee, Pain
- What is being tested?
- REGN5069
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 259 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 21 May 2019to 29 Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Generally in good health at the screening visit
- Body mass index (BMI) ≤39 kg/m2 at the screening visit
- Clinical diagnosis of OA of the knee on the American College of Rheumatology criteria (Altman, 1986) with radiologic evidence of OA (K-L score ≥2) at the index joint at the screening visit
- Moderate-to-severe pain in the index joint
- A history of inadequate pain relief from or intolerance to analgesics used for OA
Who cannot join
- Diagnosis of systemic diseases that may affect joints
- History or presence of osteonecrosis, destructive arthropathy, neuropathic joint arthropathy, pathologic fractures in any shoulder, hip, or knee joint(s), hip dislocation (prosthetic hip dislocation is eligible), or knee dislocation (patella dislocation is eligible) at the screening visit. Presence of subchondral insufficiency fracture on screening films or MRI as assessed by the central imaging reader.
- Is scheduled for a joint replacement surgery to be performed during the study period
- Received an intra-articular injection of hyaluronic acid in any joint within 90 days prior to the screening visit
- Systemic (ie, IV, oral, or intramuscular) corticosteroids within 30 days prior to the screening visit. Intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit, or to any other joint within 30 days prior to the screening visit (topical, intranasal, or inhaled corticosteroids are permitted).
- History or presence at the screening visit of multiple sclerosis, autonomic neuropathy, diabetic neuropathy, or other peripheral neuropathy
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- Significant concomitant illness including, but not limited to, psychiatric, cardiac, renal, hepatic, neurological, endocrinological, metabolic, or lymphatic disease that, in the opinion of the investigator, would adversely affect the patient's participation in the study
- History of myocardial infarction, acute coronary syndromes, transient ischemic attack, or cerebrovascular accident within 12 months prior to the screening visit
- Note: Other protocol defined inclusion/exclusion criteria apply.
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
Poland5 sites
Regeneron Study Site
Bialystok, Podlaskie Voivodeship, 15-879
Regeneron Study Site
Lublin, Lublin Voivodeship, 20-412
Regeneron Study Site
Warsaw, Masovian Voivodeship, 02 - 777
Regeneron Study Site
Zamość, Lublin Voivodeship, 22-400
Regeneron Study Site
Zgierz, Łódź Voivodeship, 95-100
United States4 sites
Regeneron Study Site
Charleston, South Carolina, 29406
Regeneron Study Site
DeLand, Florida, 32720
Regeneron Study Site
Jupiter, Florida, 33458
Regeneron Study Site
Miami, Florida, 33143
About this study
Official title: A Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Efficacy and Safety of REGN5069 in Patients With Pain Due to Osteoarthritis of the Knee
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:
- To characterize the concentrations of functional REGN5069 in serum over time when patients are treated for up to 12 weeks
- To assess the safety and tolerability of REGN5069 compared with placebo when patients are treated for up to 12 weeks
- To measure levels of anti-drug antibodies (ADAs) against REGN5069 following multiple IV administrations
- Conditions
- Osteoarthritis of the Knee, Pain
- Being tested
- REGN5069, Matching Placebo
- Medical subject headings
- Osteoarthritis, Knee, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REGN5069Drug
Intravenous (IV) Dose every 4 weeks (Q4W)
Matching PlaceboDrug
Intravenous (IV) Dose every 4 weeks (QW4)
| Study group | Role | What they receive |
|---|---|---|
| REGN5069 Low Dose | Experimental | Randomized in a 1:1:1 ratio Receives: Drug: REGN5069 |
| REGN5069 High Dose | Experimental | Randomized in a 1:1:1 ratio Receives: Drug: REGN5069 |
| Matching Placebo | Experimental | Randomized in a 1:1:1 ratio Receives: Drug: Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 12
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to Week 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2019
- Study start21 May 2019
- Primary completion1 May 2020
- Study completion29 Oct 2020
Why it stopped: Regeneron has discontinued further clinical development of REGN5069, an antibody to GFRα3, which was previously being studied in osteoarthritis pain of the knee
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Osteoarthritis of the KneeStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 259 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03956550
- Sponsor's protocol ID
- R5069-OA-1849
- Status last verified
- Jun 2021
- First submitted
- 16 May 2019
- Last updated
- 1 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie publicly available results will be considered for sharing
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Efficacy and Safety of REGN5069 in Patients With Pain Due to Osteoarthritis of the Knee
- ClinicalTrials.gov ID
- NCT03956550
- Acronym / sponsor ID
- R5069-OA-1849
- Conditions
- Osteoarthritis of the Knee, Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Regeneron has discontinued further clinical development of REGN5069, an antibody to GFRα3, which was previously being studied in osteoarthritis pain of the knee
- Enrolment
- 259 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 May 2019 (actual)
- Primary completion
- 1 May 2020 (actual)
- Study completion
- 29 Oct 2020 (actual)
- First posted
- 20 May 2019 (actual)
- Results
- Posted 1 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To characterize the concentrations of functional REGN5069 in serum over time when patients are treated for up to 12 weeks
- To assess the safety and tolerability of REGN5069 compared with placebo when patients are treated for up to 12 weeks
- To measure levels of anti-drug antibodies (ADAs) against REGN5069 following multiple IV administrations
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| REGN5069 Low Dose | Experimental | Drug: REGN5069Randomized in a 1:1:1 ratio |
| REGN5069 High Dose | Experimental | Drug: REGN5069Randomized in a 1:1:1 ratio |
| Matching Placebo | Experimental | Drug: Matching PlaceboRandomized in a 1:1:1 ratio |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Generally in good health at the screening visit
- Body mass index (BMI) ≤39 kg/m2 at the screening visit
- Clinical diagnosis of OA of the knee on the American College of Rheumatology criteria (Altman, 1986) with radiologic evidence of OA (K-L score ≥2) at the index joint at the screening visit
- Moderate-to-severe pain in the index joint
- A history of inadequate pain relief from or intolerance to analgesics used for OA
Key exclusion criteria (9 listed)
- Diagnosis of systemic diseases that may affect joints
- History or presence of osteonecrosis, destructive arthropathy, neuropathic joint arthropathy, pathologic fractures in any shoulder, hip, or knee joint(s), hip dislocation (prosthetic hip dislocation is eligible), or knee dislocation (patella dislocation is eligible) at the screening visit. Presence of subchondral insufficiency fracture on screening films or MRI as assessed by the central imaging reader.
- Is scheduled for a joint replacement surgery to be performed during the study period
- Received an intra-articular injection of hyaluronic acid in any joint within 90 days prior to the screening visit
- Systemic (ie, IV, oral, or intramuscular) corticosteroids within 30 days prior to the screening visit. Intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit, or to any other joint within 30 days prior to the screening visit (topical, intranasal, or inhaled corticosteroids are permitted).
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 |
|---|---|---|
| REGN5069Intravenous (IV) Dose every 4 weeks (Q4W) | Drug | REGN5069 High Dose, REGN5069 Low Dose |
| Matching PlaceboIntravenous (IV) Dose every 4 weeks (QW4) | Drug | Matching Placebo |
Primary outcome
Change From Baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
Time frame: Baseline to Week 12
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.
8 secondary outcomes
Change From Baseline to Week 12 in WOMAC Total Score
Time frame: Week 12
Change From Baseline to Week 12 in WOMAC Physical Function Subscale Score
Time frame: Week 12
Change From Baseline to Week 12 in Patient Global Assessment (PGA) Score
Time frame: Week 12
Change From Baseline to Week 12 in WOMAC Stiffness Subscale Score
Time frame: Week 12
Percentage of Participants With ≥30% Improvement in WOMAC Pain Subscale Score
Time frame: Week 12
Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study
Time frame: Baseline to Week 36
Number of Imaging Abnormalities Consistent With Adjudicated Arthropathies Through End of Study
Time frame: Baseline to Week 36
Number of Participants With Presence of Anti-REGN5049 Antibody Development Through End of Study
Time frame: Baseline to Week 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. All IPD that underlie publicly available results will be considered for sharing
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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.
Clinical Trial Management study director
Regeneron Pharmaceuticals
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing REGN5069 in people with Osteoarthritis of the Knee and Pain, run by Regeneron Pharmaceuticals at 12 sites in 5 countries.
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 5 inclusion and 9 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: stopped early, as of the sponsor's last update on 1 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Poland, United States, Georgia, Moldova, Ukraine. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jul 2021.