The DENOCHARCOT trial. Efficacy of treatment with DENOsumab of an acute CHARCOT foot in patients with diabetes. A multicenter, double-blind, randomized, placebo-controlled trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden, Region Hovedstaden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Nervous System Diseases [C10]

Trial duration

1 Nov 2020 → ongoing

Decision date (initial)

2024-07-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-515365-34-00

EudraCT number

2018-003724-36

ClinicalTrials.gov

NCT04547348

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

The aim of the present trial is to assess the efficacy of treatment of acute Charcot foot in diabetes patients with Prolia® on clinical relevant Outcomes in a randomized, double blind, placebo-controlled trial.

Conditions and MedDRA coding

diabetic acute Charcot foot (Charcot neuroarthropathy)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Age 18-80 years AND Type 1 or type 2 diabetes (diagnosed diabetes for more than 3 months) AND Diagnosed with acute Charcot foot defined as a unilateral red, swollen and warm foot, with a difference of skin temperature of more than 2 °C compared with the unaffected foot and with sign of Charcot on either x-rays of the foot, MRI, bone scintigram or PET/CT and Peripheral neuropathy: Previously diagnosed and/or biothesiometri: > 25 V or lack of sensation of 10 grams monofilament on 1. toe at the acute Charcot foot.

Exclusion criteria 1

1. • Duration of the acute Charcot foot for more than 3 months (at the screening visit). • Existing foot ulcer on the affected foot, unless the ulcer is very superficial, in healing and with no signs of infection and no increased surrounding skin temperature compared to the contralateral foot. • Previous acute or chronic Charcot of the affected foot • Planned surgery on the acute Charcot foot • Infection (cellulitis or osteomyelitis) of the affected foot (clinically and/or radiologically proven) • Previous midfoot or proximal to mid foot amputation of the affected foot • Hypocalcemia (Serum Calcium <2.1 mmol/L or Calcium ion < 1.12 mmol/L) • Vitamin D deficiency (Serum 25-hydroxyvitamin D < 50 nmol/L) • Renal failure (serum creatinine >200 mmol/L or eGFR < 30 ml/min). • Treatment with Denosumab within the last 12 months. • Have a known hypersensitivity to Denosumab • History of osteonecrosis of the jaw. • Poor oral hygiene, which is defined as within 3 months of a tooth extraction, dental implants or mandibular surgery • Planned mandibular surgery or dental implants within the next 12 months. • Prior non-traumatic vertebral fracture • Treatment with medication known to affect bones within the last 12 months (such as bisphosphonates, Forsteo®, calcitonin, Protelos®, selective estrogen receptor modulators, glucocorticoids and sex hormones) • Active or chronic liver disease *Chronic liver disease is defined as clinical history of decompensated chronic liver disease (ascites, encephalopathy or variceal bleeding) *Acute Liver disease is defined as an INR of > 1.5 (in the absence of the use of Warfarin) and AST and ALT > 2 x ULN • History of inflammatory arthropathies (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, autoimmune arthropathy) • Pre-existing medical condition judged to preclude safe participation in the study • Current treatment with cytotoxic drugs or with systemically administered glucocorticoids • Abuse of alcohol or drugs, or presence of any condition that in the Investigators opinion may lead to poor adherence to study protocol • Pregnancy, breast feeding or planning pregnancy or not using adequate contraceptive methods. The following contraceptive products are considered to be safe: Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections). • Likely inability to comply with the visits because of planned activity • Use of any investigational product with the last month. • Use of any drug or any other reason which in the Investigator’s opinion could interfere with the outcome of the treatment of the acute Charcot foot. • Cancer, or any clinically significant disease or disorder, except for conditions associated to the diabetes, which in the Investigator’s opinion could interfere with the results of the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time from first injection of IP until the time point where the acute Charcot foot is clinically healed/in remission, ie. the temperature difference at the site maximum temperature on the affected Charcot foot is < 2 degrees Celsius compared to the similar site on the contra-lateral foot, measured using an infrared thermometer, and edema and redness of the skin has subsided – at two subsequent visits 4 weeks apart.

Secondary endpoints 1

1. Fraction of clinical healed participants at each study visit. Fraction of healing on X-rays and MRI (or PET/CT or Scintigram) at the time of clinical healing and at the End of trial. Number of relapses (defined as need for/prescription of off- loading with cast of the Charcot foot again) ...

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Bispebjerg Bakke 23

City

Copenhagen Nv

Postcode

2400

Country

Denmark

Scientific contact point

Organisation

Bispebjerg Hospital, Department of Endocrinology

Contact name

Ole Lander Svendsen

Public contact point

Organisation

Bispebjerg Hospital, Department of Endocrinology

Contact name

Ole Lander Svendsen

Third parties 1

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Bispebjerg Bakke 23

City

Copenhagen Nv

Postcode

2400

Country

Denmark

Scientific contact point

Organisation

Region Hovedstaden

Contact name

Ole Lander Svendsen

Public contact point

Organisation

Region Hovedstaden

Contact name

Ole Lander Svendsen

Third parties 1

Locations

1 EU/EEA country · 8 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 6 files

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

Application history

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