ICH GCP - EU Clinical trials Registry - 2023-000033-33 (NL)

Strona Badania kliniczne Nct

Summary
EudraCT Number:	2023-000033-33
Sponsor's Protocol Code Number:	83631
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2023-05-03
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

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2023-000033-33

A.3

Full title of the trial

Short-term safety and efficacy of ketohexokinase inhibition in patients with hereditary fructose intolerance.

Korte termijn effectiviteit en veiligheid van ketokexokinase remming in patiënten met hereditaire fructose intolerantie.

A.3.1

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

Short-term safety and efficacy of inhibition of fructose metabolism in people with hereditary fructose intolerance.

Korte termijn veiligheid en werking van het blokkeren van fructose metabolisme in mensen met hereditaire fructose intolerantie.

A.3.2

Name or abbreviated title of the trial where available

KHKi in HFI

KHK-remming in HFI

A.4.1

Sponsor's protocol code number

83631

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	Maastricht University
B.1.3.4	Country	Netherlands
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	Pfizer Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Maastricht University
B.5.2	Functional name of contact point	Nutrition and Movement Sciences
B.5.3	Address:
B.5.3.1	Street Address	Universiteitssingel 50
B.5.3.2	Town/ city	Maastricht
B.5.3.3	Post code	6200MD
B.5.3.4	Country	Netherlands
B.5.6	E-mail	e.koene@maastrichtuniversity.nl

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	No
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	PF-06835919
D.3.2	Product code	PF-06835919
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PF-06835919
D.3.9.2	Current sponsor code	PF-06835919
D.3.9.3	Other descriptive name	PF-06835919
D.3.9.4	EV Substance Code	SUB203449
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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

Hereditary fructose intolerance

Hereditaire fructose intolerantie

E.1.1.1

Medical condition in easily understood language

fructose intolerance

fructose intolerantie

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10019878
E.1.2	Term	Hereditary fructose intolerance
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10017397
E.1.2	Term	Fructose intolerance hereditary
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10072104
E.1.2	Term	Fructose intolerance
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

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

To assess the effects of short-term treatment with PF-06835919 on intestinal, hepatic and renal fructose tolerance, and intrahepatic lipid content in patients with hereditary fructose tolerance

Het bepalen van het effect van de ketohexokinase remmer, PF-06835919, op fructose tolerantie in de darmen, lever en nieren in patiënten met hereditaire fructose intolerantie

E.2.2

Secondary objectives of the trial

N/A

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Participants are able to provide signed and dated written informed consent prior to any study specific procedures
-Use of effective contraception (only applicable to premenopausal women; a pregnancy test will be performed in these women at baseline)
-Aged ≥ 18 years
-Hereditary fructose intolerance, diagnosed by either genetic testing, liver biopsy or intravenous fructose tolerance test*

*Not applicable for healthy controls

-Deelnemers zijn in staat om ondertekende en gedateerde geschreven geïnformeerde toestemming te verschaffen voorafgaand enige studie specifieke procedures
-Leeftijd ≥ 18 jaar
-Gebruik van effectieve contraceptie (alleen toepasselijk op premenopausale vrouwen; een zwangerschapstest zal gedaan worden bij deze vrouwen bij baseline).
-Hereditaire fructose intolerantie, gediagnostiseerd door genetische testen, leverbiopt of intraveneuze fructose tolerantie test*

*niet toepasselijk op de gezonde controles

E.4

Principal exclusion criteria

-Diabetes Mellitus
-Any contra-indication for MRI scanning*
-Patients with congestive heart failure and and/or severe renal and/or liver insufficiency
-Uncontrolled hypertension
-Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator which would possibly hamper our study results
-Use of drugs that inhibit organic anion transporting polypeptide B1 (OATPB1) transporters (e.g. rifampicin, gemfibrozil, cyclosporine, erythromcyin and clarithromycin)*
-Subjects who do not want to be informed about unexpected medical findings
-Pregnancy*
-Treatment with irinotecan*

*only applicable for HFI patients

-Diabetes Mellitus
-Elke contra-indicatie voor MRI scans*
-Patiënten met congestief hartfalen en/of ernstige nierfalen en/of leverfalen
-ongecontroleerde hypertensie
-Deelname aan een klinische studie met een onderzoeksproduct in de voorafgaande 3 maanden, of als zodanig beoordeeld door de onderzoeker, die onze resultaten kan beïnvloeden
-Medicatie gebruik dat organisch anion transporterend polypeptide B1 (OATPB1) transporters blokkeert (e.g. gemfibrozil, cyclosporine, erythromcyin en clarithromycin)*
-Deelnemers die niet willen worden geïnformeerd over onverwachte medische bevindingen
-Zwangerschap*
-Behandeling met irinotecan*

*Alleen toepasselijk voor HFI patiënten

E.5 End points

E.5.1

Primary end point(s)

The primairy endpoint is fructose tolerance, assessed at the level of the intestines (abdominal complaints), liver (serum glucose and phosphate levels) and kidney (urinary pH, glucose, phosphate and amino acids)

De primaire uitkomstmaat is fructose tolerantie, beoordeeld op het niveau van de darmen (abdominale klachten), lever (serum glucose en fosfaat concentraties), en nier (pH-graad van urine, fosfaat en amino zuren).

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint will be evaluated every testday, after either a glucose or fructose tolerance test.

De primaire uitkomstmaat zal elke testdag worden beoordeeld na een glucose of fructose tolerantie test.

E.5.2

Secondary end point(s)

The secondary endpoints are:
-Intrahepatic lipid content (measured using 1H-MRS at baseline and completion)
-Blood pressure (measured at baseline and completion)
-Glycosylated transferrin (measured at baseline and completion)

De secundaire uitkomstmaten zijn:
- Hoeveelheid levervet (gemeten met 1H-MRS) op baseline en na voltooiing van de volledige 9 dagen medicatie
- Bloeddruk op baseline en na voltooiing van de volledige 9 dagen
- Glycosylated transferrin op baseline en na voltooiing van de volledige 9 dagen

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoints will be evaluated at baseline, and after participants have taken PF-06835919 daily for 9 days.

De secundaire uitkomstmaten zullen worden beoordeeld op baseline en nadat deelnemers PF-06835919 dagelijks voor 9 dagen.

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

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

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

Geen

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-05-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-05-01

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-11-30

Strona Badania kliniczne Nct

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