Prospective pilot trial to address the feasibility and safety of treatment with oral Zinc in GNAO1 associated disorders (ZINCGNAO1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Cologne

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

30 Jul 2024 → 4 Aug 2025

Decision date (initial)

2024-06-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Donations of the German parents asscociation: “GNAO1-Gemeinsam nicht allein e.V."

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety

To investigate feasibility and safety of an oral therapy with zinc in patients affected by GNAO1.

Secondary objectives 10

1. Level of Motor-Skills measured by Change of Gross-motor function measure(GMFM-66).
2. Quality of life measured by CP-Child Questionnaire for the caregivers and Canadian occupational performance measure (COPM)
3. Level of Dystonia measured by Change of Burke-Fahn-Marsden Dystonia Rating scale (BFMDRS)
4. Level of dyskinesia measured by Abnormal involuntary movement scale (AIMS) and a Movement log of the parents
5. Changes in general behavior including level of alertness, better sleep
6. Changes in Seizure logs (times, duration, frequency)
7. Serum controls of zinc to measure efficacy of oral zinc administration
8. Serum ferritin and copper detect potential deficiencies, caused by regular zinc administration and therefore reduced uptake
9. Analyze of the Microbiome in stool
10. Changes of Motor Skills and level of dyskinesia in correlation to patient specific variant in GNAO1

Conditions and MedDRA coding

GNAO1 associated disorders

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. GNAO1 associated neurological disorder, documented by either (1)Proven pathogenic or likely pathogenic mutation in GNAO1 or (2)a variant of unknown significance in GNAO1 and clinical symptoms likely to be consistent with GNAO1 as determined by the investigators and at least one of the common symptoms of GNAO1: Movement disorder (dystonia, chorea, ataxia, stereotypic movements, clonic), central muscular hypotonia, epilepsy, global developmental delay
2. Age: 6month-30years
3. Gross-Motor-Function measure-66 (GMFM-66) ≤ 75
4. Written informed consent prior to any trial-related procedure by parents or legal guardian
5. Stable on following concomitant treatments for at least 3 months prior to trial inclusion: anti-seizure medication (ASD); baclofen, Deep brain stimulation settings

Exclusion criteria 8

1. Treatment of Zinc in the last 4 months before inclusion
2. Known other genetic variants that are known to cause symptoms like observed in GNAO1-related disorders, additional to the proven GNAO1 mutation
3. Implantation of Deep brain stimulation planned during the duration of the trial, i.e. in the six months after inclusion
4. Start of intrathecal baclofen therapy planned during the duration of the trial, i.e. in the six months after inclusion
5. Known allergy/hypersensitivity to the scheduled trial drug
6. Concomitant participation in other clinical drugs with investigational drugs or with competing interventions
7. Sexually active participants who are not willing to use/ not using a highly effective contraception method with a pearl-index < 1. Sexually active participants resp. their partner, unless surgically sterile, must be using a highly effective contraception method (including oral, transdermal, injectable or implanted contraceptives, IUD, using a condom of the sexual partner or sterile sexual partner) and must agree to continue using such precautions during the whole study period
8. Pregnant women and nursing mothers

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The feasibility is measured by the actual days that zinc was taken in the right dosage. If the IMP was taken in the scheduled dosage at least on 80% of the days it is assumed to be feasible.
2. The safety is measured by regular evaluation of the AEs

Secondary endpoints 10

1. Level of Motor-Skills: measured by the Gross-Motor-Function measure-66 (GMFM-66) at visit 0, 2 and 3.
2. Quality of Life: (1) as reported by the Caregiver Priorities & Child Health Index of Life with Disabilities (CP-Child) Questionnaire for the caregivers (Visit 0, 2 and 3) and (2) as reported in the Canadian Occupational Performance Measure (COPM) (Visit 0 and 3).
3. The level of dystonia is measured by the Burke-Fahn-Marsden Dystonia Rating scale (BFMDRS) at visit 0, 2 and 3.
4. General behaviour including level of alertness and better sleep is recorded by the parents in a daily logbook that has to been filled out during the trial
5. Frequency, time and duration of seizures is also recorded by the parents in a logbook
6. Serum levels of zinc at visit 0, 2, 3 to measure the efficacy of oral zinc administration
7. Serum level of ferritin and copper at visit 0, 2, 3 to detect potential deficiencies, caused by reduced uptake because of the regular zinc administration
8. Analyzation of the microbiome in the stool by the collaborating laboratory to detect any changes respect to the GNAO1 affected cells of the intestinal
9. Level of dyskinesia measured by Abnormal involuntary movement scale (AIMS) at visit 0, 2 and 3 and a Movement log for parents
10. As far as feasible, depending on patient numbers, the individual results will be put in correlation to the specific variant of the patient to see if the outcome is influenced by the specific variant

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Cologne

Sponsor organisation

University Of Cologne

Address

Albertus-Magnus-Platz 1

City

Cologne

Postcode

50923

Country

Germany

Scientific contact point

Organisation

University Of Cologne

Contact name

Moritz Thiel

Public contact point

Organisation

University Of Cologne

Contact name

Moritz Thiel

Third parties 7

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

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

Application history

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