Clinical Trials Register

Summary
EudraCT Number:	2022-003205-29
Sponsor's Protocol Code Number:	CAP2022-1
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-11-23
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2022-003205-29

A.3

Full title of the trial

A Phase II, randomized, placebo – controlled crossover proof-of-concept study to evaluate efficacy and safety of distal jejunal-release dextrose beads formulation (APHD-012) in subjects with a pathological Oral Glucose Tolerance Test (OGTT)

Randomizované, placebom kontrolované klinické skúšanie fázy II s prekrížením liečby, na preukázanie konceptu, a vyhodnotenie účinnosti a bezpečnosti dextrózových guličiek, ktoré sa uvoľňujú v distálnom jejune (APHD-012), u osôb s patologickým orálnym glukózovým tolerančným testom (OGTT)

A.3.1

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

A Phase II, randomized, placebo – controlled crossover study to evaluate efficacy and safety of dextrose beads formulation (APHD-012) released in small intestine in subjects with a Oral Glucose Tolerance Test (OGTT) out of normal ranges

Randomizované, placebom kontrolované klinické skúšanie fázy II s prekrížením liečby na vyhodnotenie účinnosti a bezpečnosti dextrózových guličiek (APHD-012), ktoré sa uvoľňujú v tenkom čreve u osôb s orálnym glukózovým tolerančným testom (OGTT) mimo normálnych hodnôt

A.4.1

Sponsor's protocol code number

CAP2022-1

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	Aphaia Pharma US LLC
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Aphaia Pharma US LLC
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	Aphaia Pharma US LLC
B.5.2	Functional name of contact point	Kai Deusch
B.5.3	Address:
B.5.3.1	Street Address	100 road 198
B.5.3.2	Town/ city	Juncos
B.5.3.3	Post code	PR 00777
B.5.3.4	Country	United States
B.5.6	E-mail	deusch@aphaiapharma.com

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	APHD-012
D.3.2	Product code	APHD-012
D.3.4	Pharmaceutical form	Coated granules in sachet
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	Dextrose Monohydrate
D.3.9.1	CAS number	77938-63-7
D.3.9.3	Other descriptive name	DEXTROSE MONOHYDRATE BP
D.3.9.4	EV Substance Code	SUB29052
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	12
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Coated granules in sachet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subjects with a pathological Oral Glucose Tolerance Test (OGTT)

pacienti s patologickými hodnotami orálneho glukózového tolerančného testu (OGTT)

E.1.1.1

Medical condition in easily understood language

Patients with Oral Glucose Tolerance Test (OGTT) out of normal ranges

Pacienti u ktorých sú výsledky orálneho glukózového tolerančného testu (OGTT) mimo normálnych hodnôt

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	24.0
E.1.2	Level	LLT
E.1.2	Classification code	10065542
E.1.2	Term	Prediabetes
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess change from baseline in AUC0-2h values of Oral Glucose Tolerance Test (OGTT) as measured in blood samples.

E.2.2

Secondary objectives of the trial

- Evaluate changes in prespecified biomarkers and clinical outcome measures (e.g. fasting plasma glucose, HOMA IR).
- Assess safety and tolerability in population with a pathologic Oral Glucose Tolerance Test (OGGT).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female subjects 18 – 70 years of age
2. Fully vaccinated against SARS-CoV-2. Full Vaccination means having received all recommended doses of a COVID-19 vaccine listed by either of WHO-Emergency Use Listing (WHO-EUL), FDA or EMA or a mix and match series composed of any heterologous combination of WHO-EUL/FDA/EMA-approved or authorized COVID-19 vaccines. Alternatively, a proven recovery from a COVID-19 infection in combination with at least one vaccination with a WHO, FDA, EMA listed vaccine qualifies as a full vaccination. The vaccination program must have been completed at least two weeks prior Informed Consent Form (ICF) signed. For the avoidance of doubt, the vaccination scheme received shall bein compliance with the current rules defined by the relevant health authorities in the US or Europe.
3. Body mass index 25-35 kg/m2
4. Subjects with an impaired glucose tolerance defined as:
HbA1c values ≥5.7% and ≤ 6.4%
and/or
Impaired glucose tolerance (glucose between 140 and 199 mg/dL at the 2 hours of the Oral Glucose Tolerance Test (OGTT)) with or without impaired fasting glucose (fasting glucose between 100 and 125 mg/dL)
5. Stable body weight: gain or loss in body weight ≤ 5% body weight over last 3 months
6. History of at least one unsuccessful effort of lifestyle modification (e.g. behavioural intervention, dieting, physical activity) to loose >5% of body weight, completed at least 3 months prior to screening. Subject may have been treated with either diet or exercise alone.
7. Female subjects are not pregnant or lactating, are surgically sterilized, postmenopausal (no menses for the previous 12 months). Female subjects of childbearing potential agree to undergo pregnancy tests and to use an appropriate method of contraception (i.e. surgical sterilization, intrauterine contraceptive device, oral contraceptive, diaphragm, or condom in combination with contraceptive cream, jelly, or foam or abstinence).
8. Male subjects agree to apply proper birth control and to not donate sperm.
9. Male and female subjects agree to continue to use birth control for at least 28 days after the last dose.
10. Willingness to undergo screening and all study procedures and examinations (i.e., physical examinations and laboratory investigations before and after the treatment periods) and to wear a continuous glucose monitoring device.
11. Ability to comprehend subject information and willingness to sign the informed consent.

E.4

Principal exclusion criteria

1. Evidence of type 2 diabetes defined by fasting plasma glucose ≥ 126 mg/dL; 2-hour OGTT glucose ≥ 200 mg/dL
2. Type I diabetes mellitus
3. HbA1c ≥ 6.5%
4. History of proliferative retinopathy or maculopathy
5. Active COVID-19 infection proven by antigen positive Covid Test
6. Treatment with any medication for weight loss within the past 3 months before screening. Examples include: Orlistat (Xenical®, Alli®), Bupropion-naltrexone (Contrave®), Liraglutide (Saxenda®), semaglutide (Wegovy®), Phentermine-topiramate (Qsymia®).
7. Prior or planned weight loss surgery for obesity
8. Recent (within past 12 months) or planned endoscopic treatment for obesity. Examples include: Intragastric balloon (e.g. OrberaTM, ReShapeTM, ObalonTM), Natural Orifice Transluminal Endoscopic Surgery, endoscopic oral-assisted bariatric surgery procedures, including but not limited to: restorative obesity surgery, endoluminal (ROSE), StomaphyXTM, duodenojejunal bypass liner (e.g. EndobarrierTM), transoral gastroplasty (e.g., TOGA), endoscopic closure devices (e.g., Apollo OverStitchTM).
9. Proven history of bulimia or anorexia nervosa
10. Eating habits consisting of eating relevant amounts of food throughout the night (after 10 p.m.; except if working on night shifts)
11. Treatment with injectable anti-diabetic medications in the last 3 months (e.g., GLP-1 receptor agonists, insulin)
12. Treatment with dipeptidyl peptidase-4 inhibitors in the last 3 months
13. Confirmed medical history of liver cirrhosis
14. Positive test on Viral hepatitis (HbsAG, HCV)
15. Positive test on Human immunodeficiency virus (HIV)
16. Cholestatic disease
17. Alcohol-related liver disease including alcoholic fatty liver, alcoholic hepatitis and alcoholic cirrhosis evidenced by confirmed history of alcohol use, abnormal liver function tests defined below, and complete blood count (CBC), and/or liver biopsy.
18. Abnormal liver function tests:
Transaminases:
Alanine aminotransferase (ALT) ≥ 3x upper limit of normal (ULN);
or Aspartate aminotransferase (AST) ≥ 3x ULN;
or Alkaline phosphatase (ALP) ≥ 2.5x ULN;
or total bilirubin ≥ 2x ULN
19. Stage 4 hypertension (systolic blood pressure (SBP) ≥ 180, diastolic BP (DBP) ≥ 110)
20. History or presence of any uncontrolled cardiovascular, pulmonary, hepatobiliary, renal, hematological, gastrointestinal, endocrinologic, immunologic, dermatologic, neurological, psychiatric, metabolic, musculoskeletal, or malignant disease (except conditions accepted for inclusion) which the clinical investigator considers a disqualification for participation in the study.
21. Prior or current treatment with drugs aimed to treat abnormal glucose homeostasis including oral antidiabetics, incretin analogues and/or insulin.
22. History of uncontrolled illness (e.g. depression, psychosis) or behaviour that at the discretion of the investigator might confound the study results or pose additional risk in administering the study procedures.
23. Illicit drug abuse (marijuana, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines)
24. Alcohol abuse, defined by regular consumption of alcohol within 6 months before screening defined by intake of  7 drinks/week for females,  14 drinks/week for males where 1 drink equals to 150 mL of wine or 360 mL of beer or 45 mL of hard liquor
25. Participation in another investigational drug/biologic or medical device study within 30 days of screening or will be enrolled in another investigational drug or medical device study or any study in which active subject participation is required outside normal hospital data collection during the course of the study.
26. Failure to provide informed consent.
27. Unwillingness or inability to comply with the study protocol or study-related procedures.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in AUC0-2h values of Oral Glucose Tolerance Test (OGTT) as measured in blood samples

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 113

E.5.2

Secondary end point(s)

Fasting plasma glucose concentrations
- HOMA-IR
Exploratory outcome measures
- Systolic blood pressure (SBP)
- Diastolic blood pressure (DBP)
- Heart rate (HR)
- Triglycerides
- Cholesterol
Total
LDL
HDL
- Fasting plasma insulin
- HbA1c
- Alanine transaminase (ALT)
- Aspartate transaminase (AST)
- Gamma Glutamyl Transferase (GGT)
- Continuous Glucose Monitoring (CGM) metrics (e.g. Daily average glucose, time in range, time below/above range, daily glucose variability, AUC0-2h of OGTT as measured with CGM)

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 113

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

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

proof of concept

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

The last visit of the last subject is the defined end of the study.

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

E.8.9.2

In all countries concerned by the trial months

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

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-02-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-01-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-02-13

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