CANDESARTAN for Chronic cluster headache

Inclusion criteria

• {"criterion_text":"- Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent"}
• {"criterion_text":"- Participants who have chronic cluster headache according to ICHD-3 criteria present at inclusion"}
• {"criterion_text":"- Participants must have had chronic cluster headache for > 1 year and usual cluster headache periods should last > 5 weeks"}
• {"criterion_text":"- Participants that if they have other ongoing concomitant infrequent primary headache types, such as episodic migraine or episodic tension-type headache, can clearly differentiate them from attacks of CH based on the quality of pain and associated symptoms"}
• {"criterion_text":"- Participants must experience between 4 attacks per week and a maximum of 8 attacks per day of severe or very severe intensity on average over the two-week baseline period"}
• {"criterion_text":"- The cluster headache at the time of inclusion and baseline should exhibit characteristics consistent with the participant's typical symptoms"}
• {"criterion_text":"- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies: No contraceptive/barrier requirements needed for male participants; For women of childbearing potential (WOCBP), it is required that there be no ongoing pregnancy or planned pregnancies during the study period. The use of a contraception method as listed in section 10.4.2 in the protocol is mandatory."}
• {"criterion_text":"- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol"}

Exclusion criteria

• {"criterion_text":"- ECH excludes the participant from the study"}
• {"criterion_text":"- Any history of severe renal insufficiency"}
• {"criterion_text":"- Hypersensitivity to candesartan, placebo or any of the excipients"}
• {"criterion_text":"- Severe hepatic impairment and/or cholestasis"}
• {"criterion_text":"- Current or recent (within last 12 months) treatment with candesartan for any indication"}
• {"criterion_text":"- Current use of other antihypertensive medication(s) including verapamil and metoprolol (see section 6.9)"}
• {"criterion_text":"- Recent initiation or change in dose (<4 months) of preventive CH medication with galcanezumab or other parenteral CGRP-inhibitors, or botulinum toxin (<6 months, fewer than 3 treatment sessions). Stable dosage with CGRP-inhibitors > 4 months and/or botulinum toxin > 6 months (at least 3 treatment sessions) is allowed"}
• {"criterion_text":"- Treatment with greater occipital nerve blocks containing steroids or oral/parental prednisone/prednisolone < 4 weeks"}
• {"criterion_text":"- Recent initiation (< 4 weeks) of oral preventive CH medications including indomethacin or oral gepants (preventive use)"}
• {"criterion_text":"- Current use of potassium supplements"}
• {"criterion_text":"- Current use of spironolactone"}
• {"criterion_text":"- CH due to known structural lesion"}
• {"criterion_text":"- Current use of Lithium"}
• {"criterion_text":"- Current or recent (< 4 weeks) participation in other relevant clinical studies"}
• {"criterion_text":"- CCH, but with shorter bouts lasting <5 weeks with attack free periods <3 months should be excluded"}
• {"criterion_text":"- Abuse of alcohol or illicit drugs"}
• {"criterion_text":"- Women of child-bearing age without contraception"}
• {"criterion_text":"- Inability to understand study procedures and to comply with them for the entire length of the study"}
• {"criterion_text":"- Any previous surgical treatment for CH like deep brain stimulation, microvascular decompression, gamma knife radiosurgery, neurostimulation or other invasive treatments"}
• {"criterion_text":"- Current chronic migraine or chronic tension-type headache (migraine or tension-type headache that has met the ICHD-3 criteria for these conditions within the past 12 months)"}
• {"criterion_text":"- Pregnancy, planning to get pregnant, inability to use contraceptives (See inclusion criteria, number 7), and lactating"}
• {"criterion_text":"- Severe depression or other psychiatric disorder that may interfere with the treatment"}
• {"criterion_text":"- Other severe chronic pain conditions that may interfere with the study, including trigeminal neuralgia"}
• {"criterion_text":"- History of angioneurotic edema due to candesartan or other antihypertensive medication(s)"}
• {"criterion_text":"- Primary hyperaldosteronism (Conn’s syndrome))"}

Primary endpoints

• {"endpoint_text":"- Change from baseline in the weekly frequency of severe and very severe cluster headache attacks during the two four-week blinded phases","definition_or_measurement_approach":"Change from baseline in weekly frequency of severe and very severe cluster headache attacks measured during two four-week blinded phases compared with a two-week baseline (pre-randomization diary phase)."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in total attack frequency of cluster headache attacks during the four-week blinded phases","definition_or_measurement_approach":"Change from baseline in total attack frequency during the four-week blinded phases compared with baseline diary period."}
• {"endpoint_text":"- 50% responder rate (proportion of participants with ≥50% reduction of severe and very severe attacks/biweekly from baseline) over the blinded phases","definition_or_measurement_approach":"Proportion of participants achieving ≥50% reduction in biweekly severe/very severe attacks relative to baseline over the blinded phases."}
• {"endpoint_text":"- 30% responder rate (proportion of participants with ≥30% reduction of severe and very severe attacks/biweekly from baseline) over the blinded phases","definition_or_measurement_approach":"Proportion of participants achieving ≥30% reduction in biweekly severe/very severe attacks relative to baseline over the blinded phases."}
• {"endpoint_text":"- 50% responder rate for each two weeks in the blinded phases","definition_or_measurement_approach":"Biweekly 50% responder rate assessed separately for each two-week interval during the blinded phases."}
• {"endpoint_text":"- Time to sustained freedom of attacks for ≥2 months after the current bout","definition_or_measurement_approach":"Time from randomization to sustained period of ≥2 months without attacks after the current bout."}
• {"endpoint_text":"- Change from baseline in mean intensity of severe and very severe attacks over the blinded periods","definition_or_measurement_approach":"Change in mean intensity (patient-reported) of severe/very severe attacks during blinded periods compared with baseline."}
• {"endpoint_text":"- Change from baseline in biweekly number of acute pharmacological therapies over the blinded period","definition_or_measurement_approach":"Change in the biweekly count of acute pharmacological treatments used during blinded periods versus baseline."}
• {"endpoint_text":"- Change from baseline in biweekly number of inhaled oxygen treatments over the blinded period","definition_or_measurement_approach":"Change in the biweekly number of inhaled oxygen treatments used during blinded periods compared with baseline."}
• {"endpoint_text":"- Percentage of patients who rated their improvement as 'very much better' (score of 1) or 'much better' (score of 2) on the Patient Global Impression of Improvement (PGI-I) scale at weeks 4, 12 and 20 after baseline","definition_or_measurement_approach":"Proportion of participants with PGI-I score of 1 or 2 at weeks 4, 12 and 20 post-baseline."}
• {"endpoint_text":"- Percentage of patients who showed an improvement of more than 1 point on the HADS Anxiety (HADS-A) and/or Depression (HADS-D) subscales at weeks 4, 12 and 20 after baseline","definition_or_measurement_approach":"Proportion of participants with >1 point improvement on HADS-A and/or HADS-D at weeks 4, 12 and 20."}
• {"endpoint_text":"- Assessment and evaluation of participants for suicide-related events (behavior and/or ideation) as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) at baseline","definition_or_measurement_approach":"C-SSRS assessment at baseline to evaluate suicide-related events (behavior/ideation)."}
• {"endpoint_text":"- Percentage of patients who reported a reduction of CH-specific disability at weeks 4, 12, and 20 after baseline as measured by the Cluster Headache Impact Questionnaire (CHIQ)","definition_or_measurement_approach":"Proportion of participants reporting reduction in CH-specific disability at weeks 4, 12 and 20 using CHIQ."}
• {"endpoint_text":"- Change in the biweekly frequency of severe/very severe cluster headache attacks during the OTP compared with the biweekly frequency in the second blinded phase","definition_or_measurement_approach":"Change in biweekly frequency during the open treatment period (OTP) compared with biweekly frequency in the second blinded treatment period."}
• {"endpoint_text":"- Time to recurrence of severe/very severe attacks in participants during OTP who were attack-free at the end of the second blinded phase","definition_or_measurement_approach":"Time from end of second blinded phase to recurrence of severe/very severe attacks during OTP for participants who were attack-free at that time."}
• {"endpoint_text":"- Proportion of participants achieving ≥50% reduction in use of weekly acute treatments in OTP compared with baseline","definition_or_measurement_approach":"Proportion achieving ≥50% reduction in use of weekly acute treatments during OTP vs baseline."}
• {"endpoint_text":"- Time to recurrence of severe/very severe attacks in the last wash-out phase in participants taking candesartan in the OTP","definition_or_measurement_approach":"Time to recurrence of severe/very severe attacks during the last wash-out phase among participants receiving candesartan in OTP."}
• {"endpoint_text":"- Proportion of participants who rate their overall condition as “much improved” or “very much improved” on PGIC at Week 8 of OTP, referenced to their status at the end of the second BTP","definition_or_measurement_approach":"Proportion rating 'much improved' or 'very much improved' on PGIC at Week 8 of OTP compared with status at end of second blinded treatment period."}

Methods

• Study brochures: 'CandClus brochure chronic' (documents present for DK and NO) — targeted to patients with chronic cluster headache; country-specific versions for Denmark and Norway are listed.
• Recruitment film / film manuscript: 'Recruitment material film manus CandClus2' (DK and NO versions) — audiovisual materials for patient recruitment.
• Printed materials/trifold: 'CandClus Trifold Episodic Chronic' (DK and NO) — patient-facing printed recruitment material.
• Headache diary recruitment function: 'Headache diary recruitment function' (document present) — recruitment via diary functionality (document titled as recruitment function).
• Local recruitment arrangements: 'K1_Recruitment arrangements NO Chronic CandClus2' and corresponding DK recruitment arrangement documents — site-level recruitment procedures are provided.
• Public contact / study contact details: CandClus study contact (NorHEAD) contact email candclus2@helse-bergen.no and NorHEAD Studieinfo hodepine@ntnu.no are provided as study contact channels for patient enquiries.

Denmark

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

04-11-2025

Processing Time Days

18

Number Of Sites

1

Number Of Participants

10

Norway

Earliest CTIS Part Ii Submission Date

22-10-2025

Latest Decision Or Authorization Date

05-11-2025

Processing Time Days

14

Number Of Sites

8

Number Of Participants

34

Primary sponsor

Full Name

Helse Bergen HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway

Third parties

• {"country":"Norway","full_name":"Kragero Tablettproduksjon AS","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}

Co-sponsors

• St. Olavs Hospital HF