Repeated corticosteroid injections around the Greater Occipital Nerve (GON) as prophylactic treatment in chronic cluster headache

2024-514311-10-00 Protocol NL79665.058.22 Therapeutic confirmatory (Phase III) Ended

Start 10 Aug 2024 · End 8 Apr 2026 · Status Ended · 1 EU/EEA countries · 2 sites · Protocol NL79665.058.22

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 50
Countries 1
Sites 2

Cluster headache

To show that repeated GON-injections are a safe, well-tolerated, convenient, and cost-effective therapy to rapidly and long-term reduce the attack frequency in chronic cluster headache.

Key facts

Sponsor
Leids Universitair Medisch Centrum (LUMC)
Participant type
Patients
Age range
18-64 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Trial duration
10 Aug 2024 → 8 Apr 2026
Decision date (initial)
2024-08-09
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
ZonMW

External identifiers

EU CT number
2024-514311-10-00
EudraCT number
2021-006687-25
ClinicalTrials.gov
NCT05324748

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Efficacy, Safety

To show that repeated GON-injections are a safe, well-tolerated,
convenient, and cost-effective therapy to rapidly and long-term reduce
the attack frequency in chronic cluster headache.

Secondary objectives 3

  1. To determine f the effect of one GON-injection predict the effects of subsequent GON-injections.
  2. The median GON-injection interval.
  3. The tolerability of repeated GON-injections .

Conditions and MedDRA coding

Cluster headache

VersionLevelCodeTermSystem organ class
25.0 LLT 10086874 Chronic cluster headache 100000004848

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Age ≥18
  2. Chronic cluster headache (International Classification of Headache Disorders – third edition; ICHD-3)
  3. Ictal pain must be always at the same side
  4. ≥4 weekly attacks of cluster headache in the prospective one-month baseline observation period
  5. On a stable regimen of cluster headache prophylactics for >4 weeks prior to onset of study treatment and agreeing not to increase the dose and not starting a new cluster prophylactic during the study period

Exclusion criteria 7

  1. Contra-indication against, or current use of, corticosteroids
  2. Occipital nerve stimulation (ONS)
  3. Use of anticoagulation medication or a known bleeding disorder
  4. Inability to use an electronic diary to monitor individual attacks and other items
  5. Other headaches if the patient cannot reliably distinguish them from attacks of cluster headache
  6. Current use of prophylactic medication for other headaches -
  7. Pregnancy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Retention rate (= time between the first injection and end-of-treatment; survival curves verum vs. placebo)

Secondary endpoints 12

  1. Frequency of daily cluster headache attacks
  2. The use of acute attack medication per day (subcutaneous sumatriptan and 100% oxygen)
  3. Mean duration and severity (1-10) of attacks
  4. Injection interval
  5. Total number of injections in study period
  6. Proportion of participants still in study at 1 year
  7. Participants idea: did they receive placebo or verum?
  8. Physician's idea: did they administer placebo or verum?
  9. Adverse events + ultrasound structural integrity measurements greater occipital nerve
  10. Proportion of subjects with a >50% and 100% reduction in attack frequency
  11. Daily quality of life (EQ 5D)
  12. Healthcare use & productivity losses

Investigational products

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

Test 1

Depo-Medrone 40 mg/ml Suspension for Injection.

PRD1182064 · Product

Active substance
Methylprednisolone Acetate
Pharmaceutical form
SUSPENSION FOR INJECTION
Route of administration
SUBCUTANEOUS INJECTION
Max daily dose
80 mg/ml milligram(s)/millilitre
Max total dose
960 mg/ml milligram(s)/millilitre
Max treatment duration
12 Week(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
PL 00057/0963
MA holder
PFIZER LIMITED
MA country
XI
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

NaCl 0,9 % B. Braun, solution injectable

PRD9621454 · Product

Active substance
Sodium Chloride
Substance synonyms
SODIUM CHLORID
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS INJECTION
Max daily dose
2 ml millilitre(s)
Max total dose
24 ml millilitre(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
V07AB — SOLVENTS AND DILUTING AGENTS, INCL. IRRIGATING SOLUTIONS
Marketing authorisation
BE128125
MA holder
B.BRAUN MELSUNGEN AG
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation
Leids Universitair Medisch Centrum (LUMC)
Address
Albinusdreef 2
City
Leiden
Postcode
2333 ZA
Country
Netherlands

Scientific contact point

Organisation
Leids Universitair Medisch Centrum (LUMC)
Contact name
Rolf Fronczek

Public contact point

Organisation
Leids Universitair Medisch Centrum (LUMC)
Contact name
Rolf Fronczek

Sponsor responsibilities

Article 77 implementation
Leids Universitair Medisch Centrum (LUMC)

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ended 50 2
Rest of world 0

Investigational sites

Netherlands

2 sites · Ended
Leiden University Medical Center
Neurolo, Albinusdreef 2, 2333 ZA, Leiden
Canisius Wilhelmina Ziekenhuis
Neurology, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Netherlands 2024-08-10 2026-04-08

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 Onderzoeksprotocol NL7966505822 5
Recruitment arrangements (for publication) K1 Recruitment Procedure 1
Subject information and informed consent form (for publication) L1 informatiebrief en toestemmingsformulieren_CWZ 6
Subject information and informed consent form (for publication) L1 informatiebrief en toestemmingsformulieren_LUMC 6
Summary of Product Characteristics (SmPC) (for publication) E2 SmPC Methylprednisolon 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-07-16 Netherlands Acceptable with conditions
2024-08-09
2024-08-09
2 SUBSTANTIAL MODIFICATION SM-1 2024-10-11 Netherlands Acceptable with conditions 2024-11-26