Clinical Trials Register

Summary
EudraCT Number:	2017-004352-33
Sponsor's Protocol Code Number:	ALLN-177-301
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-05
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-004352-33

A.3

Full title of the trial

Evaluate the Safety and Efficacy of ALLN-177 in Patients with Enteric Hyperoxaluria: A Phase III Randomized, Placebo-Controlled Study

Valutazione della sicurezza e dell’efficacia di ALLN-177 in pazienti affetti da iperossaluria enterica: Studio di fase III, randomizzato, controllato verso placebo

A.3.1

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

Evaluate the Safety and Efficacy of ALLN-177 in Patients with Enteric Hyperoxaluria: A Phase III Randomized, Placebo-Controlled Study

Valutazione della sicurezza e dell’efficacia di ALLN-177 in pazienti affetti da
iperossaluria enterica: Studio di fase III, randomizzato, controllato verso placebo

A.3.2

Name or abbreviated title of the trial where available

Evaluate the Safety and Efficacy of ALLN-177 in Patients with Enteric Hyperoxaluria: A Phase III Ran

Valutazione della sicurezza e dell’efficacia di ALLN-177 in pazienti affetti da iperossaluria enteri

A.4.1

Sponsor's protocol code number

ALLN-177-301

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	ALLENA PHARMACEUTICALS INCORPORATED
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	Allena Pharmaceutical, 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	Medpace
B.5.2	Functional name of contact point	Clinical operation
B.5.3	Address:
B.5.3.1	Street Address	Theresienhoehe 30
B.5.3.2	Town/ city	Monaco
B.5.3.3	Post code	80339
B.5.3.4	Country	Germany
B.5.4	Telephone number	004989895571899
B.5.5	Fax number	0049898955718165
B.5.6	E-mail	a.fraunhofer@medpace.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	ALLN-177 (Oxalate decarboxylase)
D.3.2	Product code	-
D.3.4	Pharmaceutical form	Capsule, hard
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.3.9.1	CAS number	9024-97-9
D.3.9.2	Current sponsor code	ALLN-177
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	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
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	Capsule, hard
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

Enteric Hyperoxaluria

Iperossaluria enterica

E.1.1.1

Medical condition in easily understood language

excessive urinary oxalate excretion

eccessiva escrezione di ossalato nelle urine

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	SOC
E.1.2	Classification code	10038359
E.1.2	Term	Renal and urinary disorders
E.1.2	System Organ Class	10038359 - Renal and urinary 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

Determine the efficacy of ALLN-177 in reducing UOx excretion in subjects with enteric HOx

Determinare l’efficacia di ALLN-177 nel ridurre l’escrezione di UOx in soggetti
affetti da iperossaluria (HOx) enterica

E.2.2

Secondary objectives of the trial

Evaluate the safety of ALLN-177 in subjects with enteric HOx

Valutare la sicurezza di ALLN-177 in soggetti affetti da HOx enterica

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed and dated the Institutional Review Board (IRB)/Ethics Committee (EC)-approved
informed consent form (ICF) before undergoing any Screening procedure

2. Is = 18 years of age at Screening

3. Has a history of HOx (confirmed by documented UOx excretion = 50 mg/24 hr in the most
recent 24-hour urine collection obtained within 6 months prior to Screening) that is secondary
to a known underlying enteric disorder associated with malabsorption (e.g., bariatric surgery,
Crohn’s disease, short bowel syndrome, or other malabsorption syndrome)
- Note: Subjects with known or suspected HOx (e.g., history of kidney stones or oxalate
nephropathy) without a 24-hour urine collection to determine UOx excretion within = 6
months of Screening may perform a pre-screening 24-hour urine collection after providing
appropriate consent. This 24-hour urine collection can also be used to satisfy Inclusion
Criterion No. 4, if obtained within 6 weeks prior to Screening

4. Has adequate (i.e., appropriate ratio of creatinine [mg]/body weight [kg] for gender)
24-hour urine collection at Screening, with resulting UOx excretion = 50 mg/24 hr

5. Has provided 2 adequate 24-hour urine collections at Baseline, with average urinary oxalate =
50 mg/24 hr (and neither is < 40 mg/24 hr).

6. For subjects taking concomitant medication for management of kidney stone risk factors (e.g.,
pyridoxine, thiazides, citrate supplements, allopurinol): has been on a stable dose regimen for
>8 weeks prior to and during Screening, with no changes in dosing (dose level or dosing
frequency) anticipated during the remainder of the study
7. For female subjects: Is either medically incapable of pregnancy (e.g., has undergone
hysterectomy or tubal ligation or has experienced prolonged [= 1year prior to Screening]
amenorrhea) or, if a woman of childbearing potential, has a negative Screening serum
pregnancy test, is not pregnant or nursing at Screening, and agrees to use an effective
(approved by the Investigator) method of birth control for the duration of the study

1. Modulo di consenso informato approvato dal Comitato etico (CE) firmato e datato prima
dell’esecuzione di qualsiasi procedura di screening
2. Età =18 anni allo screening
3. Anamnesi di HOx (confermata da un’escrezione documentata di UOx =50 mg/24 ore nella
raccolta delle urine delle 24 ore più recente ottenuta entro 6 mesi prima dello screening)
secondaria a un noto disturbo enterico sottostante associato a malassorbimento (per es. chirurg
bariatrica, morbo di Crohn, sindrome dell’intestino corto o altra sindrome da malassorbimento)
¿ Nota: i soggetti con HOx nota o sospetta (per es. anamnesi di calcolosi renale o nefropatia
da ossalati) che non dispongono di una raccolta delle urine delle 24 ore per la
determinazione dell’escrezione di UOx entro =6 mesi dallo screening possono effettuare
una raccolta delle urine delle 24 ore prima dello screening, dopo aver fornito opportuno
consenso. Questa raccolta delle urine delle 24 ore può essere utilizzata anche per soddisfar
il criterio di inclusione n. 4, se ottenuta entro 6 settimane prima dello screening
4. Disponibilità di adeguata raccolta delle urine delle 24 ore (ovvero, rapporto creatinina
[mg]/peso corporeo [kg] appropriato per il sesso) allo screening, con escrezione risultante di
UOx =50 mg/24 ore
5. Esecuzione al basale di 2 raccolte delle urine delle 24 ore adeguate, con concentrazione media
di ossalato urinario =50 mg/24 ore (e nessuno dei due valori <40 mg/24 ore)
6. Per i soggetti che assumono una terapia concomitante per la gestione dei fattori di rischio
associati allo sviluppo di calcolosi renale (per es. piridossina, tiazidici, integratori di citrato,
allopurinolo): posologia stabile per =8 settimane prima dello screening e durante lo stesso,
senza alcuna modifica del trattamento (livello di dosaggio o frequenza di somministrazione) prevista nel resto dello studio
7. Per i soggetti di sesso femminile: impossibilità medica di avviare una gravidanza (per es.
soggetto sottoposto a isterectomia o legatura delle tube o che ha manifestato amenorrea
prolungata [=1 anno prima dello screening]) oppure, nel caso di una donna in età fertile,
soggetto con esito negativo del test di gravidanza sul siero eseguito allo screening, non in stato
di gravidanza o allattamento allo screening e che accetta di utilizzare un metodo contraccettivo
efficace (approvato dallo sperimentatore) per la durata dello studio

E.4

Principal exclusion criteria

1. Has > 30% variability in the ratio of creatinine (mg)/body weight (kg) among the three 24-hour
urine samples collected prior to randomization (1 at Screening, 2 at Baseline)
2. Is in acute renal failure or has an estimated glomerular filtration rate (eGFR)
< 30 mL/minute/1.73 m
2
at Screening
3. Has HOx with a known cause other than underlying enteric disorder associated with
malabsorption (e.g., primary HOx)
4. Is unable or unwilling to discontinue Vitamin C supplementation at Screening and for the
duration of the study
5. Any clinically significant findings during Screening, any ongoing clinically significant illness
requiring changes in management within 4 weeks prior to or during Screening (e.g., flare of
inflammatory bowel disease), or any planned surgical/invasive procedure during the study
6. Malignancy or treatment for malignancy within 12 months prior to screening with the
exception of localized basal cell or squamous cell skin cancer or any cancer in situ
¿ Note: Subjects whose malignancy is in remission and who are on a stable dose of chronic
suppressive or maintenance therapy are not excluded
7. Has an active autoimmune disorder or other condition requiring therapy with high doses of
systemic steroids (i.e., >10 mg/day prednisone or equivalent) or intensification of other
immunosuppressant therapy within 4 weeks prior to or during Screening
¿ Note: Stable subjects on low chronic or maintenance doses of steroids or other
immunosuppressant drugs, including transplant recipients, are not excluded
8. Has received study drug (ALLN-177 or placebo) in any other ALLN-177 clinical study, or
participation in another drug or device clinical trial within 30 days prior to or during Screening
9. Is not, per Investigator judgment, an ideal clinical trial candidate due to a personal issue (e.g.,
unwillingness/inability to comply with protocol) or medical condition (e.g., mental illness,
laboratory abnormalities) that is likely to impede successful study completion

1. Variabilità >30% nel rapporto creatinina (mg)/peso corporeo (kg) tra i tre campioni di urine
delle 24 ore raccolti prima della randomizzazione (1 allo screening, 2 al basale)
2. Insufficienza renale acuta o velocità di filtrazione glomerulare stimata <30 ml/minuto/1,73 m
allo screening
3. HOx con causa nota diversa da un disturbo enterico sottostante associato a malassorbimento
(per es. HOx primaria)
4. Impossibilità o indisponibilità a interrompere l’integrazione di vitamina C allo screening e per
la durata dello studio
5. Qualsiasi risultato clinicamente significativo durante lo screening, qualsiasi malattia
clinicamente significativa in corso che richieda modifiche nella gestione entro le 4 settimane
precedenti o durante lo screening (per es. riacutizzazione di malattia infiammatoria intestinale)
o qualsiasi procedura chirurgica/invasiva in programma durante lo studio
6. Tumore maligno o trattamento per tumore maligno entro 12 mesi prima dello screening, eccet
tumore cutaneo basocellulare o squamocellulare localizzato o qualsiasi tumore in situ
¿ Nota: i soggetti il cui tumore maligno è in remissione e che sono in trattamento con una
dose stabile di terapia soppressiva cronica o di terapia di mantenimento non saranno esclus
7. Patologia autoimmune attiva o altra condizione che richieda una terapia con alte dosi di steroi
sistemici (ovvero >10 mg/die di prednisone o equivalente) o l’intensificazione di altra terapia
immunosoppressiva nelle 4 settimane precedenti o durante lo screening
¿ Nota: i soggetti stabili in trattamento con basse dosi croniche o di mantenimento di steroi
o altri farmaci immunosoppressori, inclusi i riceventi trapianto, non saranno esclusi
8. Trattamento con il farmaco dello studio (ALLN-177 o placebo) nell’ambito di qualsiasi altro
studio clinico su ALLN-177 o partecipazione ad un’altra sperimentazione clinica su farmaci o
dispositivi nei 30 giorni precedenti o durante lo screening
9. A giudizio dello sperimentatore, candidato non ideale per la sperimentazione clinica a causa di
un problema personale (per es. indisponibilità/impossibilità di aderire al protocollo) o una condizione medica (per es. malattia mentale, anomalie di laboratorio) che potrebbe ostacolare
positivo completamento dello studio

E.5 End points

E.5.1

Primary end point(s)

Percent change from baseline in 24-hour UOx excretion during Weeks 1-4

Variazione percentuale rispetto al valore basale dell’escrezione di UOx nelle 24 ore
durante le Settimane 1-4

E.5.1.1

Timepoint(s) of evaluation of this end point

Weeks 1-4

1-4 settimane

E.5.2

Secondary end point(s)

Secondary Efficacy Endpoints:
• Proportion of subjects with a = 20% reduction from Baseline in 24-hour UOx
excretion during Weeks 1-4 (alternate primary efficacy endpoint for ex-US
submission)
• Ordered categorical analysis of the percentage change from Baseline in 24-hour
UOx excretion during Weeks 1-4
• Analysis of efficacy parameters by bariatric surgery vs. other enteric condition
subgroup
Exploratory Endpoint
• Change from Baseline to Week 4 in urine supersaturation of calcium oxalate

Endpoint secondari di efficacia:
• Percentuale di soggetti con riduzione ¿20% rispetto al valore basale dell’escrezione
di UOx nelle 24 ore durante le Settimane 1-4 (endpoint primario di efficacia
alternativo per la presentazione al di fuori degli Stati Uniti)
• Analisi categoriale ordinata della variazione percentuale rispetto al valore basale
dell’escrezione di UOx nelle 24 ore durante le Settimane 1-4
• Analisi dei parametri di efficacia in base al sottogruppo della chirurgia bariatrica
rispetto ad altra condizione enterica
Endpoint esplorativo
• Variazione dal basale alla Settimana 4 nella sovrasaturazione urinaria di ossalato di
calcio

E.5.2.1

Timepoint(s) of evaluation of this end point

week 1-4

1-4 settimane

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

France

Germany

Italy

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

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:

100

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

124

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

2018-10-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-09-13

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials