Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.

NCT03027557 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1809872016-001510-20
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The only known cure for primary hyperparathyroidism is surgical removal of one or more parathyroid glands. Some patients however, do not fulfill criteria for surgery or do not want to undergo a procedure due to fear of the associated risks. Therefore a medical alternative is warranted. This study aims to evaluate the effects of Denosumab alone, and in combination with Cinacalcet, as a medical treatment for patients suffering from primary hyperparathyroidism, with mild osteoporosis. To the best of our knowledge no previously reported randomized controlled trial has investigated the use of denosumab in primary hyperparathyroidism. 60 patients will be enrolled in three different treatment-groups: 20 receiving both Denosumab and Cinacalcet, 20 Denosumab and placebo and 20 placebo and placebo. Patients included do not meet the criteria for, or have no wish for a surgical procedure. By combining the two drugs, this study could possibly contribute to the discovery of a realistic medical alternative to surgery. It is expected that the therapy will be able to both control s-calcium and s-intact parathyroid hormone (iPTH), and simultaneously enhance bone-structure. The therapy thus has the potential of preventing fractures and possibly other long-term effects of primary hyperparathyroidism such as formation of kidney stones, and coronary calcification. Another objective of this project is to investigate whether the combined therapy can facilitate an actual reset of the Calcium-sensing receptor, and thereby de facto cure the disease.

Conditions

Primary Hyperparathyroidism; Parathyroid Adenoma; Parathyroid Hyperplasia

Keywords

Primary Hyperparathyroidism; Parathyroid Adenoma; Parathyroid Hyperplasia; Cinacalcet; Denosumab; Drug Therapy; Bone Mineral Density; Calcium

Outcome Measures

Primary Outcomes (8)

• Change in Lumbar Spine Bone Mineral Density

  Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

  Baseline,one year

• Change in Total Hip Bone Mineral Density

  Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

  Baseline,one year

• Change in Femoral Neck Bone Mineral Density

  Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

  Baseline,one year

• Change in 1/3 Forearm Bone Mineral Density

  Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

  Baseline,one year

• Percentage Change in Lumbar Spine Bone Mineral Density

  Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

  Baseline,one year

• Percentage Change in Total Hip Bone Mineral Density

  Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

  Baseline,one year

• Percentage Change in Femoral Neck Bone Mineral Density

  Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

  Baseline,one year

• Percentage Change in 1/3 Forearm Bone Mineral Density

  Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

  Baseline,one year

Secondary Outcomes (26)

• Change in Volumetric BMD for the Lumbar Spine.

  Baseline, one year

• Mean P-calcium During Treatment.

  Monthly up to one year.

• Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX)

  Change from baseline at 48 weeks reported.

• Median Agatstons Score Final

  Baseline, one year

• Patients With Nephrolithiasis Final Scan.

  Patients with nephrolithiasis at one year reported.

Other Outcomes (1)

• Safety Measures

  Monthly up to one year.

Study Arms (3)

Combined treatment.

EXPERIMENTAL

20 subjects will be treated with combined 60mg denosumab bi-annually , 30 mg cinacalcet daily and 50 micrograms vitamin-D daily.

Drug: Cinacalcet 30 mg Tablet; Drug: Denosumab Inj 60 mg/ml

Monotherapy

ACTIVE COMPARATOR

20 subjects will receive 60mg denosumab bi-annually, placebo and 50 micrograms vitamin-D daily.

Drug: Denosumab Inj 60 mg/ml; Other: Placebo tablets

Placebo

PLACEBO COMPARATOR

20 subjects will receive a saline injection bi-annually (blinded), placebo-tablets and 50 micrograms vitamin-D daily.

Other: Placebo tablets; Other: Saline Injection (Placebo)

Interventions

Cinacalcet 30 mg Tablet DRUG

Participants in one arm will receive 30 mg cinacalcet each day.

Also known as: Mimpara, Sensipar

Combined treatment.

Denosumab Inj 60 mg/ml DRUG

Participants in two arms will receive 60 mg Denosumab biannually.

Also known as: Prolia, Xgeva

Combined treatment.; Monotherapy

Placebo tablets OTHER

Participants in two arms will receive one placebo-tablet each day.

Monotherapy; Placebo

Saline Injection (Placebo) OTHER

Participants in one arm will receive saline injections as placebo for denosumab.

Also known as: Sodium Chloride (NaCl) Fresenius "Kabi"

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women of 18 years of age or older.
• T-score by Dual X-ray Absorptiometry (DXA) between -1,0 og -3,5

You may not qualify if:

• Medical history of diseases leading to hypercalcaemia other than Primary Hyperparathyroidism.
• Moderately - Severely decreased liver function (alanine aminotransferase \>250u/l, gamma-glutamyl transferase\>150u/l, Bilirubin \>30)
• Medical record of heart failure
• Risk factors of prolonged corrected QT interval (QTc).
• Open lesions from oral surgery.
• Primary diseases of the bone other than osteoporosis.
• Patients suffering from kidney disease or renal failure.
• Patients under treatment with thiazide or lithium.
• Medical record of generalized seizures or epilepsy.
• Active malignant disease.
• Known allergies towards the specified medicinal products (IMPs).
• Pregnancy or breastfeeding.
• Fertile women who do not agree to the usage of effective contraception.
• Other circumstances, evaluated by the responsible investigator, making the subject unsuitable for participation.

Sponsors & Collaborators

• Peter Vestergaard: lead
• Aalborg University: collaborator

Study Sites (1)

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Related Publications (1)

• Leere JS, Karmisholt J, Robaczyk M, Lykkeboe S, Handberg A, Steinkohl E, Brondum Frokjaer J, Vestergaard P. Denosumab and cinacalcet for primary hyperparathyroidism (DENOCINA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2020 May;8(5):407-417. doi: 10.1016/S2213-8587(20)30063-2.

  PMID: 32333877 DERIVED

MeSH Terms

Conditions

Hyperparathyroidism, Primary; Parathyroid Neoplasms

Interventions

Cinacalcet; Tablets; Denosumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Important limitations are the relatively small number of study-participants, and the lack of a cinacalcet monotherapy-arm.

Results Point of Contact

• Title: Professor Peter Vestergaard
• Organization: Aalborg University Hospital

p.vestergaard@rn.dk

+45 97 66 36 00

Study Officials

• Julius Simoni Leere, MD

  Aalborg University and Aalborg University Hospital

  PRINCIPAL INVESTIGATOR

• Peter Vestergaard, DMSc

  Aalborg University and Aalborg University Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMSc, Consultant

Study Record Dates

• First Submitted: January 16, 2017
• First Posted: January 23, 2017
• Study Start: March 1, 2017
• Primary Completion: April 1, 2019
• Study Completion: September 12, 2019
• Last Updated: May 25, 2021
• Results First Posted: May 25, 2021

Record last verified: 2021-05

Locations

DK (1)