CAT-Trial: CGRP monoclonal Antibody for Treatment of painful diabetic neuropathy: a double-blind, multicenter, placebo-controlled, international phase II clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aarhus University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

14 Sep 2023 → ongoing

Decision date (initial)

2023-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk Foundation · Lundbeck A/S

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To assess the efficacy of eptinezumab on pain intensity as measured as the change in weekly self-reported mean pain intensity (mean pain over the last 24 h recorded every morning in every fourth week in a diary) by the average numerical rating scale (NRS) (0-10) from baseline (1 week before randomization) over 24 weeks after first administration.

Secondary objectives 2

1. To assess efficacy of eptinezumab on neuropathic pain severity as measured by the total score of Neuropathic Pain Scale (NPS) (baseline week and weeks 12 and 24)
2. To assess pain relief: complete, good, moderate, mild, none, worse (weeks 12 and 24)

Conditions and MedDRA coding

Painful diabetic polyneuropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age 18 – 75 years
2. Confirmed diagnosis of probable diabetic polyneuropathy, as defined by the Toronto consensus criteria and a TCNS > 5 or abnormal DPNCheck or abnormal NCS
3. Probable neuropathic pain as defined by the NeuPSIG guidelines
4. Symmetric distal pain worse in the distal lower extremities present for >6 months
5. Average pain score on a NRS of ≥4 during the baseline week

Exclusion criteria 13

1. Prior or current use of a CGRP mAbs or CGRP antagonists
2. Pregnant or planning to become pregnant during the duration of the study
3. Opioid regimen other than stable low dose of Tramadol (maximum 200 mg/day)
4. Lifetime history of psychosis, bipolar mania, or dementia. Patients with other psychiatric conditions whose symptoms are not controlled or who have not been adequately treated for a minimum of 6 months prior to screening are also excluded
5. Initiation of new neuropathic pain medications such as gabapentinoid medications (gabapentin, pregabalin) and/or capsaicin (Quetenza), botulinum toxin type A, serotonin/norepinephrine reuptake inhibitors (TCA or duloxetine or venlafaxine) 1 month prior to enrollment or for the duration of the randomized placebo-controlled phase of the study. Current and ongoing pain treatment will be allowed in stable dose (anticonvulsants, antidepressants, tramadol, topical treatments (excluding high dose capsaicin patch and botulinum toxin type A) (Paracetamol 1g and over-the-counter NSAIDS as needed up to four times daily are allowed as rescue medicine)
6. Suspected cause of lower extremity pain of other causes than diabetes (e.g. chemotherapy, alcohol or drug misuse, vitamin deficiency, concomitant central nervous system pathology) or patients with pain that cannot be distinguished from their neuropathic pain in the feet due to diabetes
7. The patient has a history of clinically significant cardiovascular disease, including uncontrolled hypertension, ischaemia or thromboembolic events (for example, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism)
8. BMI ≥39 kg/m2 at the screening visit
9. Peripheral arterial disease (PAD) defined as toe pressure <40mmHg, no palpable foot pulses or clinical claudicatio intermittens
10. Planned larger surgery in the treatment period
11. Chronic wounds
12. Unable to understand Danish (Danish site only)
13. All female subjects of childbearing potential must have negative result of a serum pregnancy test performed at screening. Subjects of childbearing potential must agree to use a medically approved form of birth control (abstinence, intrauterine device (IUD), oral contraception, barrier and spermicide or hormonal implant) throughout the duration of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in self-reported average pain intensity between eptinezumab treated group and placebo treated group by the average numerical rating scale (NRS) (0-10) using a modified version of the BPI from baseline (1 week before randomization) over 24 weeks after first administration.

Secondary endpoints 2

1. Difference between groups in neuropathic pain severity as measured by Neuropathic Pain Scale (NPS) at baseline, weeks 12 and 24
2. Difference in pain relief (complete, good, moderate, mild, none, worse) at weeks 12 and 24

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aarhus University Hospital

Sponsor organisation

Aarhus University Hospital

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus University Hospital

Contact name

Pall Karlsson

Public contact point

Organisation

Aarhus University Hospital

Contact name

Pall Karlsson

Third parties 1

Locations

1 EU/EEA country · 2 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 5 files

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

Application history

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