Prospective, placebo-controlled clinical trial with Aconite Pain Oil in oncological patients under-going chemotherapy to prevent chemotherapy-induced polyneuropathy (CIPN) grade II, to re-duce symptoms typical of CIPN and to improve the quality of life of patients with CIPN

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Wala-Heilmittel GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

13 Feb 2024 → ongoing

Decision date (initial)

2023-10-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

The risk of CIPN of grade II and higher in the treatment period can be reduced by 35% by using verum as compared to placebo

Secondary objectives 12

1. Reduction of the symptoms of CIPN that occurred in the course of treatment by use of verum as compared to placebo
2. Improved quality of life in patients during the course of treatment by use of verum as compared to placebo
3. Improved quality of sleep in patients during the course of treatment by use of verum as compared to placebo
4. Reduced anxiety and depression in the course of treatment by use of verum as compared to placebo
5. Patient satisfaction
6. Safety and tolerability in the course of treatment
7. Events related to chemotherapy due to CIPN in the course of treatment by use of verum as compared to placebo
8. Medication regarding CIPN in the course of treatment by use of verum as compared to placebo
9. Reduction of development of grade-III CIPN in the course of treatment by use of verum as compared to placebo
10. Regression of CIPN that occurred during chemotherapy after discontinuation of chemotherapy by continued use of verum as compared to placebo
11. No occurrence of CIPN after discontinuation of chemotherapy by continued use of verum as compared to placebo
12. Reduction of development of grade-I CIPN in the course of treatment by use of verum as compared to placebo

Conditions and MedDRA coding

chemotherapy-induced polyneuropathy (CIPN)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. A consent form, fully dated and signed by the patient and the principal investigator/investigator, is available
2. Patients with a minimum age of 18 years
3. Patients with a Karnofsky Index ≥ 70%
4. Patients with an assumed life expectancy of at least 12 months
5. Patients with solid tumours
6. Patients who are scheduled to receive unmodified chemotherapy with taxanes or platinum derivatives or their combination approved in Germany for at least 3 months (3 lunar months / 12 weeks)
7. Patients of childbearing age must provide a negative pregnancy test

Exclusion criteria 23

1. Participation in an interventional trial (with an investigational product) that is concurrent or occurred within 4 weeks prior to inclusion in this trial
2. Pregnant and breastfeeding patients or patients who are not using effective contraception (Pearl index < 1)
3. Patients treated with topical and/or internally administered medicinal products or cosmetics containing aconite (Aconitum napellus), camphor (Camphora), lavender essential oil (Lavandulae aetheroleum), and/or quartz within 4 weeks prior to inclusion in this trial
4. Patients with known hypersensitivity to camphor and/or any of the other ingredients of Aconite Pain Oil, as well as peanut or soy
5. Patients who are not expected to be able to comprehend the significance of the clinical trial, to demonstrate the necessary compliance, and/or to complete the patient questionnaire and patient diary in the German-language for language-related, cognitive, or other reasons
6. Patients with a planned application of chemotherapy at ≥4-week intervals
7. Patients with alcohol/drug/medication dependency
8. Patients with known genetic predispositions to polyneuropathies
9. Patients with previous or current polyneuropathy irrespective of cause
10. Patients with previous or current neurotoxic medication outside the planned chemotherapy protocol that has an impact on the primary endpoint (at the investigator´s discretion) and prior taxane and/or platinum derivative administration
11. Patients with the following known comorbidities that predispose them to CIPN: inadequately substituted hypothyroidism, renal insufficiency grade 4 and above, vasculitis/collagenosis, inadequately treated diabetes mellitus
12. Patients with active and/or clinically relevant infectious diseases: HIV, Lyme disease, hepatitis B/C, herpes infections
13. Known presence of multiple myeloma or non-Hodgkin’s lymphoma
14. Present neurological diseases, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and other neurological diseases that make it difficult or impossible to assess the primary endpoint according to the investigator’s opinion
15. Patients with metastases in the central nervous system
16. History of amputation of extremities
17. Patients with distal muscle weakness and/or atrophy
18. Skin lesions or other findings in the area of the extremities that make it impossible to use the investigational product (e.g., hand-foot syndrome)
19. Presence of any other serious acute or chronic organic or mental illness with severe impairment of the general condition that impairs or prevents regular participation in the trial
20. Use of co-analgesics such as gabapentin, pregabalin, amitriptyline, nortriptyline, clomipramine, imipramine, duloxetine 1 week before commencement of the trial (baseline) and intake during the trial before reaching CIPN grade III
21. Planned acupuncture for the treatment of CIPN during the trial
22. Topical application of substances such as lidocaine, capsaicin, botulinum toxin, amitriptyline, menthol to hands and/or feet up to 1 week before trial entry (baseline) and application during the trial
23. Electrotherapy on the extremities up to 1 week before the start of the trial (baseline) and during the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is defined as time to CIPN of grade II or higher. The effect of verum versus placebo is analysed using a COX regression model with the stratification variables of randomisation included as a covariate in the model. The following hypothesis is tested: H0: HR ≥ 1 vs. H1: HR < 1.

Secondary endpoints 26

1. Time to occurrence of CIPN grade III (days) (COX regression model)
2. Regression of CIPN that occurred during chemotherapy after discontinuation of chemotherapy by continued use of verum (degree of CIPN) (descriptively presented and exploratory statistical testing)
3. No occurrence of CIPN after discontinuation of chemotherapy by continued use of verum (occurrence/no occurrence) (descriptively presented and exploratory statistical testing)
4. Thermoception over the time (descriptively presented and mixed logistic regression model)
5. Tactile perception over the time (descriptively presented and mixed logistic regression model)
6. Nociception over the time (descriptively presented and mixed logistic regression model)
7. Pallaesthesia over the time (descriptively presented and mixed linear regression model)
8. Fine motor skills over the time (descriptively presented)
9. Hand strength over the time (compared to baseline and mixed logistic regression model)
10. Standing on toes over the time (descriptively presented)
11. Standing on heel over the time (descriptively presented)
12. Standing on one leg over the time (descriptively presented)
13. Achilles tendon reflex over time (descriptively presented and mixed linear regression model)
14. Radius periost reflex over the time (descriptively presented and mixed linear regression model)
15. Patellar reflex over the time (descriptively presented and mixed linear regression model)
16. Triceps reflex over the time (descriptively presented and mixed linear regression model)
17. Biceps reflex over the time (descriptively presented and mixed linear regression model)
18. PainDETECT over the time (descriptively presented and mixed linear regression model)
19. EORTC-QLQ-CIPN20 over the time(descriptively presented and mixed linear regression model)
20. EORTC-QLQ-C30 over the time (descriptively presented and mixed linear regression model)
21. Insomnia Severity Index over the time (descriptively presented and mixed linear regression model)
22. Anxiety and depression over the time (descriptively presented and mixed linear regression model)
23. Patient satisfaction over the time (descriptively presented and exploratory statistical testing)
24. Events related to chemotherapy due to CIPN (descriptively presented)
25. Medication regarding CIPN over the time (descriptively presented)
26. Adverse events (SAEs, ADRs, SADRs) (descriptively presented)

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Wala-Heilmittel GmbH

Sponsor organisation

Wala-Heilmittel GmbH

Address

Dorfstrasse 1+3, Eckwaelden Eckwaelden

City

Bad Boll

Postcode

73087

Country

Germany

Scientific contact point

Organisation

Wala-Heilmittel GmbH

Contact name

Clinical Research Study Coordination

Public contact point

Organisation

Wala-Heilmittel GmbH

Contact name

Clinical Research Study Coordination

Third parties 2

Locations

1 EU/EEA country · 26 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

Documents 7 files

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

Application history

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