REPLACE - A multi-centre, randomised, double-blinded, placebo controlled 16-weeks study to compare the effect of hydrocortisone and placebo in patients with Giant Cell Arteritis (GCA)/ Polymyalgia Rheumatica (PMR) with patient-reported symptoms of adrenal insufficiency after cessation of glucocorticoid treatment.

2024-513822-53-00 Therapeutic use (Phase IV) Ended

Start 1 Feb 2022 · End 12 Jan 2026 · Status Ended · 1 EU/EEA countries · 3 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ended
Participants planned 270
Countries 1
Sites 3

Tertiary adrenal insufficiency

We will perform the first placebo-controlled randomised controlled trial (RCT) in patients with polymylgia rheumatic and giant cell arteritis after planned cessation of glucocorticoid treatment. Our study will be the first evidence-based guidance and aid to glucocorticoid-induced adrenal u patients and thus meet an imp…

Key facts

Sponsor
Odense University Hospital
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Hormonal diseases [C19]
Trial duration
1 Feb 2022 → 12 Jan 2026
Decision date (initial)
2024-07-31
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2024-513822-53-00
EudraCT number
2020-006121-65
ClinicalTrials.gov
NCT05193396

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

We will perform the first placebo-controlled randomised controlled trial (RCT) in patients with polymylgia rheumatic and giant cell arteritis after planned cessation of glucocorticoid treatment. Our study will be the first evidence-based guidance and aid to glucocorticoid-induced adrenal u patients and thus meet an important need for many thousand patients.

Conditions and MedDRA coding

Tertiary adrenal insufficiency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

  1. Age ≥ 50 years
  2. A diagnosis of polymyalgia rheumatic or giant cell arteritis in glucocorticoid free remission for >2 week and <12 weeks after treatment with prednisolone (any dosage) for ≥12 weeks

Exclusion criteria 7

  1. Known primary or secondary adrenal insufficiency
  2. Known Cushing´s syndrome
  3. Severe comorbidity
  4. Alcohol consumption >21 units per week
  5. Planned major surgery during the study period at study entry
  6. Use of drugs that interfere with cortisol metabolism/measurements
  7. Inability to provide written informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Adrenal insufficiency symptoms (AddiQoL-30)

Secondary endpoints 6

  1. Patient reported symptoms of fatigue, questionnaire-based HRQoL other than AddiQoL-30, incidence of adrenal crises, hospitalizations and sick days
  2. Blood pressure and arterial stiffness
  3. Body composition and muscle strength
  4. Metabolic and cardiovascular risk
  5. Bone status
  6. Biological integrated cortisol status assessment

Investigational products

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

Test 1

Hydrokortison ”Orion”, tabletter

PRD1959653 · Product

Active substance
Hydrocortisone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
4480 mg milligram(s)
Max treatment duration
16 Week(s)
Authorisation status
Authorised
ATC code
H02AB09 — HYDROCORTISONE
Marketing authorisation
52357
MA holder
ORION CORPORATION
MA country
Denmark
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo

SUB21402 · Substance

Active substance
Placebo
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
0 mg milligram(s)
Max total dose
0 mg milligram(s)
Max treatment duration
16 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation
Odense University Hospital
Address
J B Winsloews Vej 4
City
Odense C
Postcode
5000
Country
Denmark

Scientific contact point

Organisation
Odense University Hospital
Contact name
Marianne Skovsager Andersen

Public contact point

Organisation
Odense University Hospital
Contact name
Marianne Skovsager Andersen

Third parties 1

OrganisationCity, countryDuties
Odense University Hospital
ORG-100007716
Odense C, Denmark On site monitoring, E-data capture, Code 8

Locations

1 EU/EEA country · 3 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Ended 270 3
Rest of world 0

Investigational sites

Denmark

3 sites · Ended
Rigshospitalet
Department of Nephrology and Endocrinology, Blegdamsvej 9, 2100, Copenhagen Oe
Odense University Hospital
Department of Endocrinology, J B Winsloews Vej 4, 5000, Odense C
Aarhus Universitetshospital
Hormon- og knoglesygdomme, J120, Palle Juul-Jensens Boulevard 165, Aarhus N

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2022-02-01 2026-01-12 2022-02-01

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.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-513822-53-00 6.0
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_ICF 1
Subject information and informed consent form (for publication) L1_SIS 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Hydrokortison 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-07-12 Denmark Acceptable
2024-07-30
2024-07-31