A phase 2, multicenter, randomized, double blind, active controlled, parallel group study assessing the analgesic effect and safety of two doses of DFL24412 in patients with chronic low back pain compared to Ketoprofen Lysine Salt (KLS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dompe' Farmaceutici S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

19 Nov 2021 → 30 Dec 2024

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513940-27-00

EudraCT number

2021-001629-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of DFL24412 80 mg-34 mg per os (p.o.) and DFL24412 40 mg-17 mg p.o. in chronic low back pain compared to KLS (80 mg) at week 1.

Secondary objectives 4

1. To further evaluate the analgesic efficacy of DFL24412 80 mg-34 mg and DFL24412 40 mg-17 mg in chronic low back pain compared to KLS 80 mg.
2. To assess the efficacy of DFL24412 compared to KLS on neuropathic component in chronic low back pain.
3. To assess the effect of DFL24412 compared to KLS on quality of life, Patient Global impression of Change, and work and mental impact.
4. To evaluate the safety of DFL24412 80 mg-34 mg and DFL24412 40 mg-17 mg in chronic low back pain compared to KLS 80 mg.

Conditions and MedDRA coding

Chronic low back pain

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Provide written informed consent before the initiation of any study-specific procedures
2. Must be 18-65 years of age at the time of signing the Informed Consent Form (ICF)
3. Have a normal physical examination (except features of CLBP as per IC 4, 5, and 6), vital signs, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal results that are judged not clinically significant by the PI and documented as such in the eCRF
4. Diagnosis of chronic low back pain (CLBP, pain localised below the costal margin and above the inferior gluteal folds with no known specific pathology, persisting/recurring for at least 3 months) with no substantial recent change in pain severity or clinical management, with or without lumbosacral radicular pain and/or radiculopathy
5. Clinically documented nociceptive and neuropathic components ((‘probable neuropathic pain’ as per International Association for the Study of Pain, IASP)
6. Report at least moderate pain (NRS ≥ 4) before randomization
7. If undergoing physical and/or exercise-based therapy for back pain, therapy must be stable at least three weeks prior to study and remain the same throughout study
8. If a female with childbearing potential, have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test; Women of childbearing age and potential must be willing to use highly effective contraception during the study and for 3 months after the last study treatment dose. Male patients and their female partners of childbearing age and potential must be willing to use effective contraception during the study and for 3 months after the last study treatment dose. Highly effective methods of birth control are listed in Appendix 4 of Protocol KLG0121.
9. Have a negative COVID-19 antigen rapid test or have received vaccination for COVID-19

Exclusion criteria 19

1. History of major thoraco-abdominal or low back surgery in the last 3 months
2. CLBP due to malignancy, fibromyalgia, ochronosis, recent trauma, infection, juvenile scoliosis or congenital malformation
3. Previous diagnosis of psychosis, bipolar disorder, schizoaffective disorder, major depressive disorder or neurological disorder
4. CLBP management requiring opioids or surgery and interventional procedures planned in the following 3 months
5. Any concomitant use of antidepressants, anticonvulsants, opioids, nonsteroidal anti-inflammatory drugs, muscle relaxants, and/or any other prohibited medication as listed in Appendix 6 of Protocol KLG0121 during the trial or being anticipated by the investigator to be required
6. Any concurrent medical condition that, in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient’s well-being
7. History of drug and/or alcohol abuse or dependence, excluding nicotine and caffeine
8. Have alanine aminotransferase or aspartate aminotransferase higher than 100 International Units per Liter (IU/L) or total bilirubin higher than 1.6 milligram per deciliter (mg/dL)
9. Have serum creatinine level higher than 1.6 mg/dL or creatinine clearance < 60, or had renal transplantation or receiving renal dialysis
10. Severe or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic diseases, symptomatic peripheral vascular disease, hemorrhagic diathesis, haemolytic anemia, systemic immune-mediated and rheumatologic disorders, or other medical condition or psychiatric conditions that, in the opinion of investigator, would compromise participation or be likely to lead to hospitalization during the course of the study
11. History of bronchial asthma, peptic ulcer, gastrointestinal bleeding, ulceration or perforation
12. Crohn’s disease or ulcerative colitis
13. Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibody (antiHCV) or human immunodeficiency virus I and II antibodies (anti-HIV I/II)
14. History of intolerance or hypersensitivity to: ketoprofen lysine salt or other drugs of the same class, gabapentin, rescue medications, component of the formulation; any history of severe drug allergy or hypersensitivity
15. Female patients who meet the following criteria: Pregnant, breast-feeding, and/or planning to become pregnant and/or breast-feed during the study
16. Treatment with any investigational product (IP) during the study and within the 3 months (or at least 5 half-lives, whichever is longer) prior to Visit 1
17. Be an employee or a relative of an employee of the investigational study center
18. Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments
19. Unable or unlikely to comply with the study protocol, to fulfill eDiary/ paper Diary and questionnaires appropriately or unsuitable for any other reason, as judged by the PI

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Change From Baseline in Average Daily Low Back Pain (LBP) Intensity as Measured by an 11-point Numeric Rating Scale (NRS) at Week 1

Secondary endpoints 15

1. Change From Baseline in Average Daily Low Back Pain (LBP) Intensity as Measured by an 11-point Numeric Rating Scale (NRS) at the follow-up visit [Time Frame:, Day 21]
2. Change from baseline in Neuropathic Pain Symptom Inventory (NPSI) score at week 1
3. Change from baseline in Douleur Neuropathique en 4 Questions (DN4) score at week 1
4. Change from baseline in Douleur Neuropathique en 4 Questions (DN4) score at the follow-up visit [ Time Frame: Day 21]
5. Number of Participants Withdrawn Due to Lack of Efficacy Week 1
6. Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 1
7. Change from Baseline in Hospital Anxiety and Depression Scale (HADS) total score at Week 1
8. Patient Global Impression of Change (PGI-C) Score Week 1
9. Change From Baseline in European Quality of Life Questionnaire-5 Dimension-5 Level (EQ-5D-5L) to Week 1
10. Change From Baseline in Work Productivity and Activity Impairment (WPAI) Instrument at Week 1
11. Number of rescue interventions up to Week 1
12. Physical examination (see 7.1.2) [time frame: end of treatment visit (Week 1) or withdrawal].
13. Vital signs: blood pressure, heart rate and Body Temperature and ECG [time frame: end of treatment visit (Week 1) or early withdrawal].
14. Safety Laboratory Tests: hematocrit, hemoglobin, red blood cells, platelets, white blood cells, differential white blood cells count, sodium, potassium, calcium, serum creatinine, urea, serum albumin, total bilirubin, fractionated bilirubin, ALT, AST, ALP, lypases and amylases [time frame: end of treatment visit (Week 1) or early withdrawal].
15. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [time frame: throughout the study].

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dompe' Farmaceutici S.p.A.

Sponsor organisation

Dompe' Farmaceutici S.p.A.

Address

Via Santa Lucia 6

City

Milan

Postcode

20122

Country

Italy

Scientific contact point

Organisation

Dompe' Farmaceutici S.p.A.

Contact name

Enrico Minnella

Public contact point

Organisation

Dompe' Farmaceutici S.p.A.

Contact name

Riccardo Vecchietti

Third parties 4

Locations

2 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications