Primary objective:Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared with placebo.Secondary objective:• Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared with placebo.• Demonstrate the efficacy of…
ID
Source
Brief title
Condition
- Tendon, ligament and cartilage disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline in Western Ontario and McMaster Universities
Osteoarthritis Index (WOMAC) pain subscale score in the index knee to the score
at Week 12.
The WOMAC pain subscale, which consists of 5 questions, will be assessed and
reported in the electronic patient reported outcomes (ePRO) device once weekly
with a 48-hour recall, using an 11-point numeric rating scale (NRS, from 0 = no
pain to 10 = pain as bad as you can imagine).
Timeframe for the assessment: from baseline (assessment at V2) to V5 (Week
12/Day 84).
Estimand
The primary comparison of interest is the difference in mean change from
baseline in 48-hour WOMAC pain subscale score at Week 12 in the index knee
using an 11-point (0-10) NRS between RTX-GRT7039 and placebo, in subjects who
initiate treatment, as if substantial changes in background medication or
addition of new analgesics were not available.
Secondary outcome
See protocol section 1.2
Background summary
Osteoarthritis is the most common chronic joint disease affecting millions of
people worldwide and a leading cause of pain and disability. Despite the
available analgesic medications, not all patients with osteoarthritis,
particularly those with advanced degenerative disease, achieve adequate pain
relief with currently available treatment options.
Grünenthal is developing RTX GRT7039 for intra-articular injection of the novel
analgesic RTX for the treatment of pain associated with osteoarthritis of the
knee.
The purpose of this Phase III trial is to confirm the efficacy and safety of
RTX GRT7039, administered as repeated intra-articular injections (i.e., second
injection at 26 weeks) of 400 ng RTX GRT7039 in subjects with moderate to
severe pain associated with osteoarthritis of the knee despite receiving
continued treatment with optimal SoC or who are unable to receive SoC treatment
due to contraindications or intolerability.
This pivotal trial is intended to be an integral part of the overall efficacy
and safety assessment of RTX GRT7039 and will be used to support a marketing
authorization application.
Study objective
Primary objective:
Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared with
placebo.
Secondary objective:
• Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared
with placebo.
• Demonstrate the efficacy of intra-articular RTX-GRT7039 on function compared
with placebo.
• To assess the safety and tolerability of intra-articular RTX-GRT7039.
Study design
This is an interventional, Phase III, double-blind, randomized,
placebo-controlled, parallel-group, multi-site, clinical trial to confirm the
efficacy and safety of repeated intra-articular injections of RTX-GRT7039
versus placebo in subjects who have moderate to severe pain associated with
osteoarthritis of the knee despite receiving continued treatment with optimal
standard of care (SoC) or who are unable to receive SoC treatment due to
contraindications or intolerability.
Approximately 450 subjects will be randomized to receive either RTX-GRT7039 or
placebo in a 1:1 ratio. In addition to continued SoC treatment, subjects will
receive 1 of the following treatments:
• Intra-articular RTX-GRT7039 400 ng injections.
• Placebo to match intra-articular RTX-GRT7039 injections.
Subjects will receive IMP into the index knee as identified by inclusion and
exclusion criteria in Section 1.3 of the protocol. Subjects will receive IMP in
1 knee only.
This trial comprises a Screening Period and a double-blind Treatment and
Follow-up Period (including a Final Visit of the Treatment and Follow-up Period
at Week 52). Each subject is expected to be in the trial for up to 56 weeks
(i.e., the Screening Period of up to 30 days followed by the 52-week Treatment
and Follow-up Period).
Subjects will each receive 2 injections of investigational medicinal product
(IMP) during the double-blind Treatment Period (on Day 1 and at Week 26). For
the second injection, subjects will receive the same IMP that was administered
at the first injection, in a double-blind manner.
Intervention
A total of 5 mL of IMP will be injected 15 minutes after ropivacaine
administration into the knee joint. Fifteen minutes prior to the
intra-articular injection of IMP, a 5 mL intra-articular injection of
ropivacaine 0.5% will be administered.
The IMP must be administered by a qualified physician experienced in the
administration of intra articular injection.
It is strongly recommended that the injection is assisted by ultrasound. If
ultrasound is unavailable, aspiration of synovial fluid is strongly
recommended. Once completed, the needle and syringe will be removed, and an
adhesive bandage applied.Once completed, the needle and syringe will be
removed, and an adhesive bandage applied.
The first IMP injection will occur at the Randomization Visit (V2/Day 1) and a
second injection of IMP will be administered at 6 months (V6/Week 26).
Re-injection is not allowed if the subject did not tolerate previous IMP
injection as judged by the investigator or if they developed hypersensitivity
to the IMP.
Study burden and risks
Potential benefits to subjects participating in this trial may include a
reduction in knee pain as well as the benefits of medical supervision from
being in a clinical trial. Risks to subjects participating in this trial are
primarily related to the currently known side effects of RTX as well as the
administration of local anesthetic (Las). In addition to drug-specific risks,
there are also the risks of the procedures used in the trial.
Given the observed reductions in knee pain, and improvements in WOMAC subscale
scores, it is anticipated that RTX-GRT7039 will be efficacious in the proposed
trial population outlined in this protocol: subjects who still have moderate to
severe pain associated with osteoarthritis of the knee despite receiving
continued treatment with optimal SoC treatment or who are unable to receive SoC
treatment due to contraindications or intolerability, an indication for which
there is currently an unmet medical need.
Across the 3 clinical trials, there was no treatment-emergent adverse events
(TEAE) related to RTX-GRT7039 resolving with sequalae, of life-threatening
intensity or leading to hospitalization or death.
For more details refer to the protocol section 8.2
Zieglerstrasse 6 -
- 52078 Aachen
DE
Zieglerstrasse 6 -
- 52078 Aachen
DE
Listed location countries
Age
Inclusion criteria
• >= 18 years of age at the screening visit.
• Body Mass Index (BMI) <= 40.0 kg/m2.
• Diagnosis of osteoarthritis of the knee based on American College of
Rheumatology criteria and functional capacity class of I-III.
• Moderate to severe osteoarthritis at baseline.
• Documented history indicating that subject has insufficient pain relief with
optimal standard of care (SoC).
• The investigator does not consider that any additional benefit can reasonably
be expected from further adjustments to the patient's pain treatment.
For the list of complete inclusion criteria refer to the protocol.
Exclusion criteria
• The subject had an intra-articular injection of either corticosteroid or
intra-articular visco-supplementation (i.e., hyaluronic acid) into the index
knee within 3 months.
• The subject had an injection of platelet-rich plasma into the index knee
within 6 months.
• The subject applied topical capsaicin on the index knee within 3 months.
• Pre-existing rapidly progressing osteoarthritis (RPOA) Type I or Type II,
osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, or
the subject has knee pain attributable to disease other than osteoarthritis.
• Other conditions that could confound discrimination of pain assessment in the
index knee.
• Clinically significant disease(s) or condition(s) that may affect efficacy or
safety assessments, or any other reason which, in the investigator's opinion,
may preclude the subject's participation in the full duration of the trial.
• History of severe allergic or anaphylactic reactions.
• History of significant trauma or surgery, or surgery planned during the trial
period, related to the knee.
For the complete list of exclusion criteria refer to the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-005029-26-NL |
| ClinicalTrials.gov | NCT05248386 |
| CCMO | NL80659.056.22 |