Summary
EudraCT Number:2021-005029-26
Sponsor's Protocol Code Number:KF7039-01
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-04-21
Trial results
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2021-005029-26
A.3Full title of the trial
A randomized, double-blind, placebo-controlled, Phase III trial to
evaluate the efficacy and safety of intra-articular injections of
RTX-GRT7039 in adult subjects with pain associated with osteoarthritis of the knee
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Comparison of RTX-GRT7039 and placebo injections for pain associated with osteoarthritis of the knee.
A.4.1Sponsor's protocol code numberKF7039-01
A.5.2US NCT (ClinicalTrials.gov registry) numberNCT05248386
A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1268-7314
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorGrünenthal GmbH
B.1.3.4CountryGermany
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportGrünenthal GmbH
B.4.2CountryGermany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationGrünenthal GmbH
B.5.2Functional name of contact pointGrünenthal Trial Information Desk
B.5.3 Address:
B.5.3.1Street AddressZieglerstrasse 6
B.5.3.2Town/ cityAachen
B.5.3.3Post code52078
B.5.3.4CountryGermany
B.5.4Telephone number+49241 569-3223
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.2Product code RTX-GRT7039
D.3.4Pharmaceutical form Concentrate for solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntraarticular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNresiniferatoxin
D.3.9.1CAS number 57444-62-9
D.3.9.3Other descriptive nameRTX, GRT1076857
D.3.9.4EV Substance CodeSUB189873
D.3.10 Strength
D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number1.6
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboConcentrate for solution for injection
D.8.4Route of administration of the placeboIntraarticular use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Moderate to severe pain associated with osteoarthritis of the knee
E.1.1.1Medical condition in easily understood language
Pain due to osteoarthritis of the knee
E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level LLT
E.1.2Classification code 10023476
E.1.2Term Knee osteoarthritis
E.1.2System Organ Class 100000004859
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared with placebo.
E.2.2Secondary objectives of the trial
• 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.
E.2.3Trial contains a sub-study No
E.3Principal 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.
E.4Principal 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.
E.5 End points
E.5.1Primary end point(s)
1) Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score in the index knee.
E.5.1.1Timepoint(s) of evaluation of this end point
1) From baseline (assessment at Visit 2) to Visit 5.
E.5.2Secondary end point(s)
1) Change in WOMAC pain subscale score in the index knee based on the 11-point numeric rating scale (NRS).
2) Change in WOMAC physical function subscale score.
3) Incidence of treatment-emergent adverse events (TEAEs). Incidence of TEAEs leading to discontinuation in the Treatment and Follow-up Period after the first and after the second injection, respectively. Incidence of related TEAEs representing structural changes of the knee joint as visualized by the imaging methods (X-ray and/or magnetic resonance imaging [MRI]).
E.5.2.1Timepoint(s) of evaluation of this end point
1) From baseline (assessment at Visit 2) to Visit 6 to Visit 10.
2) From baseline (assessment at Visit 2) to Visit 5 to Visit 6 to Visit 10.
3) From baseline (assessment at Visit 2) to Visit 10. (end of trial).
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned3
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA43
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Canada
Czechia
France
Germany
Italy
Japan
Mexico
Netherlands
Poland
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years3
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 180
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 270
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state15
F.4.2 For a multinational trial
F.4.2.1In the EEA 304
F.4.2.2In the whole clinical trial 450
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
None
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-04-21
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-06-29
P. End of Trial
P.End of Trial StatusOngoing