Clinical Trials Register

Summary
EudraCT Number:	2021-006752-14
Sponsor's Protocol Code Number:	DualActionWeightLossinIIH1
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-01-25
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2021-006752-14

A.3

Full title of the trial

Glucagone Like Peptide-1 Receptor (GLP-1R) Analogue Assisted Rapid Weight Loss Program as treatment of Idiopathic Intracranial Hypertension

Glukagonlignende peptid-receptor (GLP-1R) agonist-assisteret program med hurtigt vægttab som behandling ved Idiopatisk intrakraniel hypertension (IIH)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Program with Medically assisted Rapid Weight Loss as treatment of Idiopathic Intracranial Hypertension

Hurtigt vægttab assisteret med medicin som behandling for idiopatisk intrkraniel hypertension

A.3.2

Name or abbreviated title of the trial where available

Dual Action Weight loss in IIH

Dual Action Vægttab ved IIH

A.4.1

Sponsor's protocol code number

DualActionWeightLossinIIH1

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Rigshospitalet, Neurologisk afdeling
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novo Nordisk Foundation
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Rigshospitalet, Neurologisk afdeling
B.5.2	Functional name of contact point	Dansk Hovedpinecenter
B.5.3	Address:
B.5.3.1	Street Address	Valdemar Hansens Vej 5
B.5.3.2	Town/ city	Glostrup
B.5.3.3	Post code	2600
B.5.3.4	Country	Denmark
B.5.4	Telephone number	DK4538 63 20 62
B.5.6	E-mail	hovedpine@regionh.dk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Ozempic
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ozempic
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Injection (Noncurrent) Rectal use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Semaglutide
D.3.9.1	CAS number	910463-68-2
D.3.9.4	EV Substance Code	SUB32188
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.25 to 2.25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Idiopathic Intracranial Hypertension (IIH) is a disease in which the intracranial pressure is pathologically elevated. This can cause blindness, chronic, severe headache, and cognitive dysfunction. IIH is associated with obesity, and the only treatment which controls the disease is weight loss.

Idiopatisk intrakraniel hypertension er en relativt sjælden tilstand, hvor væsketrykket i hjernen er forhøjet. Patienter med IIH risikerer synsstab, kronisk hovedpine og koncentrationsbesvær. IIH behandles med vægttab og vanddrivende medicin. Den eneste kendte behandling, der reelt ændrer på sygdommens aktivitet, er vægttab.

E.1.1.1

Medical condition in easily understood language

Idiopathic Intracranial Hypertension (IIH) is a disease in which the brain pressure is elevated. This can cause blindness, chronic, severe headache, and cognitive dysfunction.

Idiopatisk intrakraniel hypertension er en relativt sjælden tilstand, hvor væsketrykket i hjernen er forhøjet. Patienter med IIH risikerer synsstab, kronisk hovedpine og koncentrationsbesvær.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10004277
E.1.2	Term	Benign intracranial hypertension
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

We wish to investigate whether a dual-action weight loss program combining the benefits of a very low calorie diet (VLCD) at the time of diagnosis with a GLP1R analogue for long term weight maintenance is a better treatment option than our regular calorie restricted diet, which is the current standard of care.
First, we want to investigate the use of a weight loss program for the treatment of IIH in which a 10-15 % weight loss is chieved in a very short time. We will use a randomized controlled study design with 2 treatment groups (A and B).

We hypothesize that an initial VLCD (group A) would,

1. Reduce opening pressure in new-onset IIH significantly more than our standard of care (Group B). The primary outcome is ICP after 8 weeks and weight loss (% of body weight) compared to baseline values in the two groups A and B respectively.

E.2.2

Secondary objectives of the trial

Second, we want to investigate whether the use of a GLP-1R analogue (Semaglutide®) can sustain a long-term weight loss after an initial VLCD in patients with new-onset IIH. A sustained weight loss of 10-20 % is the only known disease modifying treatment(19). We hypothesize that,

2. 8 months follow-up treatment with Semaglutide® after 8 weeks on a VLCD will result in a sustained, total weight loss of 10-20 % of total baseline body weight after 10 months in group A and a significant reduction in opening pressure after 10 months in comparison with group B.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

1) Transorbital Ultrasonography of the Optic Nerve as a marker of Intracranial Pressure in Idiopathic Intracranial Hypertension: A Longitudinal study
Objective: To investigate the usefullness of transorbital sonography as a non-invasive marker of intracranial pressure in IIH.

2) Nonalcoholic fatty liver disease in Idiopathic Intracranial Hypertension
Objective: To map the prevalence of comorbid fatty liver disease in IIH and to investigate any correlation to ammoniemia and cognitive function

1) Transorbital ultralyd af synsnerven som en markør ofr øget intrakranielt tryk i Iidopatisk Intrakraniel Hypertension: Et longitudinelt studie.
Formål: At undersøge anvendeligheden af transorbital ultralydsundersøgelse af synsnerven som en non.invasig markør for øget intrakranielt tryk i IIH.

2) Nonalkoholisk fedtlever sygdom i Idiopatisk Intrakraniel Hypertension
Formål: At undersøge prævalensen af NAFLD i patienter med IIH og undersøg eom der er korrelation med ammoniæmi og kognitiv dysfunktion.

E.3

Principal inclusion criteria

• Part 1: Suspected, new onset IIH with papilledema. Part 2: Confirmed new onset IIH with papilledema according to Friedmann et al.
• Female, 18-65 years
• BMI ≥ 27
• Written, informed consent
• Use of anticontraceptives with a failure rate of <1%

• Del 1: Mistanke om nyopstået IIH. Del 2: Bekræftet nyopstået IIH med papilødem jf. Friedmann kriterierne
• Kvinde, 18-65 år
• BMI ≥ 27
• Skriftligt informeret samtykke
• Prævention med <1 fejlprocent

E.4

Principal exclusion criteria

• Unable to provide written informed consent or participate
• Malignant IIH with visual threat that requires VP-shunting, optic nerve sheet fenestration or other surgical CSF diversion
• Pregnancy or breastfeeding
• Treatment with antidiabetics, blood-thinners or medication that may increase the risk of adverse events or affect appetite (other than topiramate or acetazolamid)
• Diabetes, congestive heart failure, severe vascular disease, pancreatitis, severe ophthalmological disorders other than IIH (e.g. retinopathy)
• History or family history of thyroid carcinomas or other MEN1/MEN2 carcinomas
• History of bariatric surgery
• Other severe/uncontrolled mental or physical disease

• Malign IIH med kirurgisk indikation
• Graviditet eller amning
• behandling med antidiabetika, blodfortyndende eller medicin, der øger risikoen for alvorlige bivirkninger eller påvirker appetitten fraset Topiramate eller Acetazolamid
• Diabetes, hjertesvigt, alvorlig vaskulær sygdom, pankreatitis, alvorlig ophthalmologisk sygdom udover IIH (fx retinopati)
• Anamnese eller familiær disposition til thyreoidea carcinomas /MEN1/MEN2 karcinomer
• Tdiligere bariatrisk kirurgi
• Andne alvorlig fysisk eller psykisk sygdom

E.5 End points

E.5.1

Primary end point(s)

The primary end point is ICP after 8 weeks and total weight lost (% of body weight).

Primære effektmål er intrakranielt tryk og vægttab (% af kropsvægt)

E.5.1.1

Timepoint(s) of evaluation of this end point

8 weeks

8 uger

E.5.2

Secondary end point(s)

• Neuroophthalmological outcome (8 weeks, 4 and 10 months)
o Degree of papilledema (Frisén grade)
o Visual field perimetric mean deviation (MD) by automated perimetry
o Optical coherence tomography (OCT) changes including enhanced depth imaging (EDI) OCT, confocal scanning laser ophthalmoscopy (cSLO) and OCT angiography (OCTA)
• Improvement in optic disc elevation and optic nerve sheath diameter assessed with ultrasonography of the optic nerves.
• Headache outcome (8 weeks, 4 and 10 months)
• Headache days per month
• Headache disability (HURT questionnaire)
• Headache intensity (8 weeks, 4 and 10 months)
• Use of headache medication
• Improvement in non-alcoholic fatty liver disease
• Percentage in remission after 10 months (absence of papilledema with or withou ICP < 25 mmH2O)
• Reduction in body fat percentage and truncal adiposity (10 months DEXA scan)
• Quality of life ( WHO QoL questionnaire (short version), 8 weeks and 10 months)
• Feasibility
• Drop-out before 8 weeks and 10-month follow-up
• Percentage of patients in ketosis (ketones in urine and blood) after 4 weeks and 8 weeks
• Difficulty following diet and patient satisfaction (scale of 0-10) at 8 weeks and after 10 months
• Use of ICP regulating medication (daily dose and length of treatment)
• Biomarkers in CSF, blood and saliva (at baseline, 8 weeks and 10 months)
• Change in cardiometabolic parameters (HOMA2IR, HbA1c, glucose, serum lipids, urine sample, etc.), samples collected with patients fasting (at baseline, 8 weeks and 10 months)
• Adverse effects including biochemical assessment

E.5.2.1

Timepoint(s) of evaluation of this end point

Eight weeks and 10 months after inclusion, respectively

Efter hhv. 8 uger og 10 måneder efter inklusion

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Patients are randomized for intervention (very low calorie diet and semaglutide) or no intervention.

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Information not present in EudraCT

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Neurologisk Afdeling, Odense Universitetshospital
G.4.3.4	Network Country	Denmark

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-03-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-08-23

P. End of Trial
P.	End of Trial Status	Ongoing

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