Clinical Trials Register

Summary
EudraCT Number:	2020-005989-34
Sponsor's Protocol Code Number:	034B20
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-04-29
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

Germany - BfArM

A.2

EudraCT number

2020-005989-34

A.3

Full title of the trial

A Phase II, randomized, double-blind, placebo-controlled, parallel-group proof-of-concept study to evaluate efficacy and safety of distal jejunal-release dextrose (Aphaia technology, AT) in obese subjects

A.3.1

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

Clinical trial involving the hospitals from different countries where patients are allocated to two groups of treatment: investigational product or the medicine which looks like the investigational product but doesn’t contain the active substance. The allocation is done by chance and neither Investigator, nor patient will know the group. The purpose of this trial is to evaluate the efficacy and safety of the investigational product. Participants should be diagnosed with obesity.

A.3.2

Name or abbreviated title of the trial where available

034B20

A.4.1

Sponsor's protocol code number

034B20

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 AG
B.1.3.4	Country	Switzerland
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 AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aphaia Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information contact
B.5.3	Address:
B.5.3.1	Street Address	Bahnhofstrasse 28
B.5.3.2	Town/ city	Zug
B.5.3.3	Post code	6300
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41417849633
B.5.6	E-mail	info@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	Aphaia Technology (AT)
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	Yes
D.3.11.13.1	Other medicinal product type	specific oral, multiple unit, delayed release formulation whose pH sensitive coating/layering of the beads ensures API release at distal jejunum

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

Obesity with/without associated endocrine and/or metabolic conditions and/or hypertension and/or NASH and/or NAFL with/without fibrosis

E.1.1.1

Medical condition in easily understood language

obesity

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	10029883
E.1.2	Term	Obesity
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Changes from baseline (CFB) in in percent weight change compared with placebo

E.2.2

Secondary objectives of the trial

• Establish proof of concept based on prespecified biomarkers and clinical outcome measures
• Assess safety and tolerability in population with or without multiple endocrine/metabolic conditions

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Obese, male and female subjects 18 – 70 years of age.
2. Body mass index 30.0 - 39.9 kg/m2 .
3. Stable body weight: gain or loss in body weight < 5 kg over last 3 months prior Day 1.
4. Trial of lifestyle modification in the past (e.g. behavioral intervention, dieting, physical activity) which did not lead to achieving desired weight loss or sustaining weight loss.
5. Obese subjects with or without one or more of the following conditions:
a) NAFL – simple steatosis based on a FibroScan™ CAP test result at Screening (CAP score ≥ 238 dB/m (steatosis grades 1 – 3) and FibroScan™ fibrosis score at Screening < 7.5 kPa (F0 – F1 fibrosis score).
b) NAFL with fibrosis – steatohepatitis based on FibroScan™ CAP test result at Screening (CAP score ≥238 dB/m (steatosis grades 1 – 3) and FibroScan™ fibrosis score at Screening ≥ 7.5 kPa and < 14 kPa (F2 – F3 fibrosis score).
c) Confirmed medical history of metabolic syndrome.
d) HOMA IR score ≥ 2.
e) Confirmed medical history of T2DM diagnosis or HbA1c ≥ 7.0 and ≤ 10 % (based on screening values).
f) High total cholesterol values (subjects on lipid-lowering medication for elevated total cholesterol or with total cholesterol ≥ 240 mg/dL (based on screening values).
g) Hypertension (subjects on antihypertensive medication or with stage 1 hypertension (SBP 140-159 mmHg and/or DBP 90-99 mmHg (based on screening values)).
6. Fully vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during COVID-19 pandemic. Full Vaccination means having received all recommended doses of a COVID-19 vaccine listed by either of World Health Organization (WHO)-Emergency Use Listing (WHO-EUL), FDA or European Medicines Agency (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 be in compliance with the current rules defined by the relevant health authorities in the US or Europe.
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. oral contraceptive steroids, intrauterine device, barrier method).
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 30 days after the last dose.
10. Findings within the range of clinical acceptability in medical history (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study), except signs and symptoms of the accepted associated conditions.
11. If on medication to manage endocrine/metabolic conditions, must be on stable doses of medication ≥ 3 months prior to Day 1:
a) As anti-diabetic therapy subjects with T2DM may be treated with either diet and exercise alone or e.g. metformin, sulphonylurea, thiazolidinediones, sodium dependent glucose co-transporter (SGLT)2-inhibitors, and bromocriptine quick release (QR) as single agents or combination therapy.
b) As lipid-lowering medication subjects may be treated with e.g. statins, fibrates, Proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitors, ezetimibe, bempedoic acid or supplements like omega-3-fatty acids.
c) As antihypertensive medication subjects may be treated with e.g. beta-blockers, Angiotensin-converting enzyme (ACE)-inhibitors or angiotensin-II-inhibitors, diuretics or calcium channel blockers.
12. Laboratory values within the accepted range, except those accepted deviations as per exclusion criteria.
13. Normal electrocardiogram (ECG) defined as Sinus Rhythm, Heart Rate 60-100 bpm, P-Q < 0.22 s, QRS < 0.12 s.
14. Vital signs within accepted ranges (normal temperature and heart rate, SBP<159 mmHg, DBP<99 mmHg measured under stabilized conditions at Screening after at least 5 minutes of rest in sitting position).
15. Willingness to undergo screening and follow-up examinations (i.e.. physical examinations and laboratory investigations before and after the treatment periods).
16. Ability to comprehend subject information and willingness to sign the informed consent.

E.4

Principal exclusion criteria

1. Incomplete COVID-19 vaccination during COVID-19 pandemic.
2. History of COVID-19 disease with no confirmation of recovery as per Centers for Disease Control and Prevention (CDC) criteria [1].
3. Prior (within past 3 months prior to Day 1) or planned treatment with weight loss medications.
4. Recent (within past 3 months prior to Day 1) weight gain or loss ≥ 5 kg.
5. Prior or planned weight loss surgery for obesity.
6. Prior or planned endoscopic treatment for obesity. Examples include:
a) Intragastric balloon (e.g. OrberaTM, ReShapeTM, Obalon);
b) Natural Orifice Transluminal Endoscopic Surgery (NOTES)/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®),
c) endoscopic closure devices (e.g., Apollo OverStitchTM)
Patients can be included if the device is removed more than 12 months ago.
7. Proven history of bulimia or anorexia nervosa.
8. Eating habits consisting of eating relevant amounts of food over the night (after 10 p.m.; except if working on night shifts).
9. Prior (within the last 3 months prior to Day 1) or planned treatment with injectable antidiabetic medications (e.g. GLP-1 receptor agonists, insulin).
10. Prior (within the last 3 months prior to Day 1) or planned treatment with dipeptidyl peptidase-4 inhibitors.
11. Confirmed medical history of cirrhosis.
12. NAFLD with cirrhosis (fibrosis score = F4 (≥ 14 kPa) as determined by screening FibroScanTM).
13. Viral hepatitis (Hepatitis B Virus (HBV), HCV.
14. Human immunodeficiency virus (HIV) positive.
15. Cholestatic disease.
16. Alcohol-related liver disease.
17. Type I diabetes mellitus.
18. HbA1c > 10%.
19. Fasting plasma glucose levels > 270 mg/dL.
20. Proliferative retinopathy or maculopathy.
21. Abnormal liver function tests:
a) Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≥ 3x upper limit of normal (ULN)
b) Alkaline phosphatase (AP) ≥ 2.5x ULN
c) Total bilirubin ≥ 1.5x ULN
22. Stage 4 hypertension (SBP ≥ 180 mmHg, DBP ≥ 110 mmHg).
23. History or presence of any uncontrolled cardiovascular, pulmonary, hepatobiliary, renal, hematologic, gastrointestinal, endocrinologic, immunologic, dermatologic, neurological, psychiatric, metabolic, musculoskeletal, or malignant disease (except conditions accepted for inclusion which the clinical investigator does not consider a disqualification for participation in the study). History or family history of medullary thyroid cancer. History of pancreatitis. Autoimmune diseases.
24. Pregnant (identified by a positive serum pregnancy test) or lactating, or not postmenopausal (no menses for at least 1 year) and of childbearing potential and not using an accepted method of birth control (i.e. surgical sterilization, intrauterine contraceptive device, oral contraceptive, diaphragm, or condom in combination with contraceptive cream, jelly, or foam or abstinence).
25. History of illness or behavior (e.g. depression, psychosis) that in the opinion of the investigator might confound the study results or pose additional risk in administering the study procedures.
26. Illicit drug abuse (marijuana, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines).
27. Alcohol abuse.
28. 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.
29. Failure to provide informed consent.
30. Unwillingness or inability to comply with the study protocol or study-related procedures.

E.5 End points

E.5.1

Primary end point(s)

• The difference in mean weight loss in percent compared with placebo at 6 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

E.5.2

Secondary end point(s)

• Proportion of subjects with ≥ 2.5 % baseline body weight loss at 6 months compared with placebo (weight loss responders)
• Proportion of subjects with ≥ 5 % baseline body weight loss at 6 months compared with placebo (weight loss responders)
• The difference in mean absolute weight loss compared with placebo at 6 months
• Change from baseline at 6 months compared with placebo, as mean absolute change and as % change of:

• Waist circumference
• SBP
• DBP
• Heart rate (HR)
• Triglycerides
• Cholesterol:
o Total
o Low density lipoprotein cholesterol (LDL-C)
o High density lipoprotein cholesterol (HDL-C)
• HOMA IR
• Fasting plasma glucose
• Fasting plasma insulin
• Hemoglobin A1c (HbA1c) – in subjects with T2DM
• Alanine transaminase (ALT)
• Aspartate transaminase (AST)
• Gamma Glutamyl Transferase (GGT)

If normal ranges are different per site, descriptive analyses per site will be performed, if necessary.

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Exploratory analysis of adiponectin level, circulating factors relevant to metabolic status, exome sequencing, miRNA 1983¬¬¬ (blood) and microbiome composition (feces)

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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Georgia

United States

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

140

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

150

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

2022-08-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-08-31

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

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