Setmelanotide in the ROHHAD-syndrome (ROH-SET study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

25 Apr 2025 → ongoing

Decision date (initial)

2025-03-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Rhythm Pharmaceuticals, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effect of setmelanotide on hypothalamic dysfunction in 5 patients with the ROHHAD syndrome after 16 weeks, 32 weeks and 52 weeks

Secondary objectives 10

1. To evaluate the effect of daily setmelanotide on body composition after 16 weeks, 32 weeks and 52 weeks, including BMI SDS, % fat free mass and liver steatosis.
2. To evaluate the effect of daily setmelanotide on hyperphagia after 16 weeks, 32 weeks and 52 weeks
3. To evaluate the effect of daily setmelanotide on temperature regulation after 16 weeks, 32 weeks and 52 weeks
4. To evaluate the effect of daily setmelanotide on respiratory function and CO2 after 16 weeks, 32 weeks and 52 weeks
5. To evaluate the effect of daily setmelanotide on circadian rhythm (sleep) after 16 weeks, 32 weeks and 52 weeks
6. To evaluate the effect of daily setmelanotide on the other symptoms of autonomous dysregulation after 16 weeks, 32 weeks and 52 weeks
7. To evaluate the effect of daily setmelanotide on quality of life after 16 weeks, 32 weeks and 52 weeks
8. To evaluate the effect of setmelanotide on resting energy expenditure after 52 weeks
9. To evaluate the adverse effects of daily setmelanotide, such as hyperpigmentation, injection sites, nausea or any other.
10. To evaluate the effect of daily setmelanotide on AVP deficiency management after 16 weeks, 32 weeks and 52 weeks

Conditions and MedDRA coding

ROHHAD syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Patient is diagnosed with ROHHAD syndrome by a pediatric endocrinologist
2. Aged 4 years and older at time of enrolment
3. Ability to communicate well with the Investigator, understand and sign the written informed consent and/or assent for patients aged <18 years, a parent/legal guardian that can sign.

Exclusion criteria 5

1. Patients with hypothalamic dysfunction attributable to other conditions (eg suprasellar tumor)
2. Patients with obesity attributable to other genetic or syndromic conditions (eg, PPL [POMC, PCSK1, LEPR, collectively], BBS, Prader-Wili syndrome)
3. History or close family history (parents or siblings) of skin cancer or melanoma (not including noninvasive, infiltrative basal or squamous cell lesion), or patient history of ocular-cutaneous albinism.
4. Inability to comply with once daily (QD) injection regimen.
5. Pregnant and/or breastfeeding or desiring to become pregnant during this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in overall scores for signs and symptoms of hypothalamic dysfunction after 16 weeks, 32 weeks and 52 weeks

Secondary endpoints 16

1. BMI SDS after 16 weeks, 32 weeks and 52 weeks
2. % fat free mass after 16 weeks, 32 weeks and 52 weeks (measured by BIA)
3. Waist circumference after 16 weeks, 32 weeks and 52 weeks
4. Presence of liver steatosis after 16 weeks, 32 weeks and 52 weeks
5. Hyperphagia scores (Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Dutch-NL) after 16 weeks, 32 weeks and 52 weeks
6. Stability of temperature (diary entries) after 16 weeks, 32 weeks and 52 weeks
7. Respiratory insufficiency after 16 weeks, 32 weeks and 52 weeks
8. Circadian rhythm: Mean sleeping scores (7 days, measured by actigraphy) and PROMIS sleep disturbance scores after 16 weeks, 32 weeks and 52 weeks
9. Level of activity after 16 weeks, 32 weeks and 52 weeks (actigraphy: mean steps in 7 days, PAQ-A/PAQ-C questionnaire)
10. Resting energy expenditure (REE) (in children age >6 years) after 52 weeks
11. Change in the other symptoms of autonomous dysregulation after 16 weeks, 32 weeks and 52 weeks as described in Tabel 2
12. Quality of live (PedsQL questionnaire scores) after 16 weeks, 32 weeks and 52 weeks
13. The difference in cardiometabolic parameters including blood pressure, lipid profile, HbA1c, liver enzymes after 52 weeks
14. Percentage of patients with adverse events such as skin hyperpigmentation, injection site reaction, nausea, headache (clinical evaluation)
15. Any serious adverse events or other adverse events
16. Change in AVP deficiency management (desmopressin dosage, need for home sodium measurements, hypo/hypernatremia) after 16 weeks, 32 weeks, 52 weeks

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Trial information desk Child Health

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Trial information desk Child Health

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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