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SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor (ACSPIRE)

Primary Purpose

Autonomous Cortisol Secretion (ACS), ACTH-Independent Cushing Syndrome, ACTH-Independent Adrenal Cushing Syndrome, Somatic

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SPI-62 dose1
SPI-62 dose 2
SPI-62 dose 3
SPI-62 dose 4
Placebo
Sponsored by
Sparrow Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autonomous Cortisol Secretion (ACS) focused on measuring Autonomous Cortisol secretion (ACS), ACTH-independent adrenal Cushing's syndrome (aCs), benign adrenal tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis and main criteria for inclusion and exclusion:

The following are the main inclusion criteria:

  • Adults able to provide informed consent.
  • Documented characteristically benign adrenal nodule, with diameter ≤ 4 cm, homogenous texture, and non-contrast computerized tomography ≤ 20 HU attenuation or proven to be non malignant.
  • Diagnosis of diabetes mellitus, pre-diabetes or impaired glucose tolerance, either untreated or on stable standard of care treatment, based on at least one of:

    • HbA1c ≥ 5.7% but not > 9.5%
    • 2-hour glucose level ≥ 7.8 mmol (140 mg/dL) on a 75 g OGTT
  • At least one additional documented cortisol-related morbidities, either untreated or on stable standard of care treatment:

    • hypercholesterolemia with total cholesterol > 3.9 mM (150 mg/dL);
    • hypertriglyceridemia with triglycerides > 2.3 mM (200 mg/dL);
    • osteopenia with bone densitometry Z-score < -2.0 or T-score < -1.0;
    • history or evidence of minimally traumatic or osteoporotic fracture; or
    • hypertension with resting supine blood pressure > 130 but < 180 mmHg systolic or > 85 but < 120 mmHg diastolic.
  • Poorly suppressible hypercortisolemia:

    • Morning serum cortisol > 50 nM (1.8 mcg/dL) after a 1 mg ONDST.
    • Subjects with dexamethasone < 3.3 nmol/L (130 ng/dL) will undergo a high-dose (8 mg) ONDST.
    • Subjects who take estrogen-containing medicines will be evaluated based on free cortisol > 2.2 nM (80 ng/dL).
    • For subjects with morning serum cortisol > 138 nM (5.0 mcg/dL) after ONDST, the Investigator will assess for adrenal Cushing's syndrome.

Exclusion Criteria:

  • Diagnosis of ACTH-dependent Cushing's syndrome, pheochromocytoma, aldosteronoma, adrenocortical carcinoma, or congenital adrenal hyperplasia, or other malignancy associated hypercortisolism including history of adrenal carcinoma.
  • History of adrenalectomy or planned adrenalectomy within 4 months after randomization.
  • Exogenous hypercortisolism.
  • Uncontrolled, clinically significant hypo- or hyperthyroidism.
  • History of idiopathic thrombocytopenia.
  • Moderately impaired renal function (estimated glomerular filtration rate < 60 mL/min/1.73m2).
  • History of cancer (other than non-melanoma skin, thyroid, or early-stage prostate cancer) within 3 years.
  • Any major surgery, or significant post-operative sequelae, within 1 month prior to informed consent or planned during the trial.
  • Pregnant or lactating.
  • Positive test for severe acute respiratory syndrome coronavirus 2 infection within 4 weeks, or hospitalization for Coronavirus disease 2019 within 6 months, prior to randomization.
  • Any other current or prior medical condition expected to interfere with the conduct of the trial or the evaluation of its results.
  • Participation in any clinical trial within 3 months prior to the first dose of study drug, or longer depending on half-life of the investigational therapy.

Sites / Locations

  • Kaiser Permanente LAMC
  • IU Simon Cancer Center - Indiana UniversityRecruiting
  • University of Michigan
  • Mayo Clinic Cancer Center (MCCC) - RochesterRecruiting
  • Washington University School of Medicine - Center for Advanced Medicine (CAM) - Diabetes Center
  • Ohio State McCampbell Outpatient CareRecruiting
  • Rhode Island HospitalRecruiting
  • Eastern Virginia Medical School - Strelitz Diabetes Center
  • Chu AngersRecruiting
  • CHU Hôpitaux de RouenRecruiting
  • Hospices Civils of LyonRecruiting
  • Lille University HospitalRecruiting
  • Hôpital de la ConceptionRecruiting
  • CHU Bordeaux Hopital HautRecruiting
  • C.M.D.T.A. NeomedRecruiting
  • Institutul National de EndocrinologieRecruiting
  • Spitalul Clinic Judeţean de Urgenţe "Sf. Spiridon"
  • Universitatea de Medicina si Farmacie Targu Mures - Spitalul Clinic Judetean de Urgenta Targu Mures
  • University Hospital of WalesRecruiting
  • Leeds Teaching Hospitals NHS TrustRecruiting
  • King's College HospitalRecruiting
  • The Christie NHS Foundation Trust
  • Manchester University NHS Foundation Trust - Wythenshawe Hospital
  • Salford Royal NHS Foundation TrustRecruiting
  • University Hospital Southampton NHS Foundation Trust - Southampton General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

SPI-62 dose 1

SPI-62 dose 2

SPI-62 dose 3

SPI-62 dose 4

Placebo

Arm Description

0.2mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.

0.6mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.

2mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.

6mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.

Placebo by mouth each morning for up to 12 weeks.

Outcomes

Primary Outcome Measures

Change in HbA1c at Week 6
HbA1c change from baseline
Change in HbA1c at week 12
HbA1c change from baseline

Secondary Outcome Measures

Full Information

First Posted
June 23, 2022
Last Updated
October 20, 2023
Sponsor
Sparrow Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05436639
Brief Title
SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor
Acronym
ACSPIRE
Official Title
SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2023 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sparrow Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This will be a study with SPI-62 to evaluate the efficacy, safety, and pharmacological effect of SPI-62 in subjects with hypercortisolism related to a benign adrenal tumor. Each subject will receive 2mg of SPI-62 daily.
Detailed Description
This is a multicenter, Phase 2 study to estimate SPI-62's effect on clinical features of hypercortisolism related to a benign adrenal tumor, including diabetes/impaired glucose tolerance, hyperlipidemia, hypertension, and osteopenia. Each subject who provides consent and meets all inclusion and exclusion criteria will participate in a screening period and an open-ended treatment period. Visits occur at screening/baseline, months 1, 3, 6, 9, and 12, and then quarter-annually.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autonomous Cortisol Secretion (ACS), ACTH-Independent Cushing Syndrome, ACTH-Independent Adrenal Cushing Syndrome, Somatic
Keywords
Autonomous Cortisol secretion (ACS), ACTH-independent adrenal Cushing's syndrome (aCs), benign adrenal tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SPI-62 dose 1
Arm Type
Experimental
Arm Description
0.2mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.
Arm Title
SPI-62 dose 2
Arm Type
Experimental
Arm Description
0.6mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.
Arm Title
SPI-62 dose 3
Arm Type
Experimental
Arm Description
2mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.
Arm Title
SPI-62 dose 4
Arm Type
Experimental
Arm Description
6mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo by mouth each morning for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
SPI-62 dose1
Intervention Description
SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 1 of drug (0.2mg).
Intervention Type
Drug
Intervention Name(s)
SPI-62 dose 2
Intervention Description
SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 2 of drug (0.6mg).
Intervention Type
Drug
Intervention Name(s)
SPI-62 dose 3
Intervention Description
SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 2 of drug (2mg).
Intervention Type
Drug
Intervention Name(s)
SPI-62 dose 4
Intervention Description
SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 2 of drug (6mg).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inactive tablets identical to SPI-62 tablets.
Primary Outcome Measure Information:
Title
Change in HbA1c at Week 6
Description
HbA1c change from baseline
Time Frame
Baseline to week 6
Title
Change in HbA1c at week 12
Description
HbA1c change from baseline
Time Frame
Baseline to week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis and main criteria for inclusion and exclusion: The following are the main inclusion criteria: Adults able to provide informed consent. Documented characteristically benign adrenal nodule, with diameter ≤ 4 cm, homogenous texture, and non-contrast computerized tomography ≤ 20 HU attenuation or proven to be non malignant. Diagnosis of diabetes mellitus, pre-diabetes or impaired glucose tolerance, either untreated or on stable standard of care treatment, based on at least one of: HbA1c ≥ 5.7% but not > 9.5% 2-hour glucose level ≥ 7.8 mmol (140 mg/dL) on a 75 g OGTT At least one additional documented cortisol-related morbidities, either untreated or on stable standard of care treatment: hypercholesterolemia with total cholesterol > 3.9 mM (150 mg/dL); hypertriglyceridemia with triglycerides > 2.3 mM (200 mg/dL); osteopenia with bone densitometry Z-score < -2.0 or T-score < -1.0; history or evidence of minimally traumatic or osteoporotic fracture; or hypertension with resting supine blood pressure > 130 but < 180 mmHg systolic or > 85 but < 120 mmHg diastolic. Poorly suppressible hypercortisolemia: Morning serum cortisol > 50 nM (1.8 mcg/dL) after a 1 mg ONDST. Subjects with dexamethasone < 3.3 nmol/L (130 ng/dL) will undergo a high-dose (8 mg) ONDST. Subjects who take estrogen-containing medicines will be evaluated based on free cortisol > 2.2 nM (80 ng/dL). For subjects with morning serum cortisol > 138 nM (5.0 mcg/dL) after ONDST, the Investigator will assess for adrenal Cushing's syndrome. Exclusion Criteria: Diagnosis of ACTH-dependent Cushing's syndrome, pheochromocytoma, aldosteronoma, adrenocortical carcinoma, or congenital adrenal hyperplasia, or other malignancy associated hypercortisolism including history of adrenal carcinoma. History of adrenalectomy or planned adrenalectomy within 4 months after randomization. Exogenous hypercortisolism. Uncontrolled, clinically significant hypo- or hyperthyroidism. History of idiopathic thrombocytopenia. Moderately impaired renal function (estimated glomerular filtration rate < 60 mL/min/1.73m2). History of cancer (other than non-melanoma skin, thyroid, or early-stage prostate cancer) within 3 years. Any major surgery, or significant post-operative sequelae, within 1 month prior to informed consent or planned during the trial. Pregnant or lactating. Positive test for severe acute respiratory syndrome coronavirus 2 infection within 4 weeks, or hospitalization for Coronavirus disease 2019 within 6 months, prior to randomization. Any other current or prior medical condition expected to interfere with the conduct of the trial or the evaluation of its results. Participation in any clinical trial within 3 months prior to the first dose of study drug, or longer depending on half-life of the investigational therapy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frank Czerwiec, MD
Phone
+1-617-465-0328
Email
fczerwiec@sparrowpharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Hooper
Phone
+1-617-465-0328
Email
shooper@sparrowpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Czerwiec, MD
Organizational Affiliation
Sparrow Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Kaiser Permanente LAMC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Withdrawn
Facility Name
IU Simon Cancer Center - Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Raters
Email
jraters@iu.edu
First Name & Middle Initial & Last Name & Degree
Cary Mariash, MD
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Withdrawn
Facility Name
Mayo Clinic Cancer Center (MCCC) - Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cas Roland
Email
Roland.cassidy@mayo.edu
First Name & Middle Initial & Last Name & Degree
Irina Bancos, MD
Facility Name
Washington University School of Medicine - Center for Advanced Medicine (CAM) - Diabetes Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Withdrawn
Facility Name
Ohio State McCampbell Outpatient Care
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aleitha Gates
Email
aleitha.gates@osumc.edu
First Name & Middle Initial & Last Name & Degree
Lawrence Kirschner, MD
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy Palmisciano
Email
apalmisciano@lifespan.org
First Name & Middle Initial & Last Name & Degree
Amanda Fernandes, MD
Facility Name
Eastern Virginia Medical School - Strelitz Diabetes Center
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Individual Site Status
Withdrawn
Facility Name
Chu Angers
City
Angers
ZIP/Postal Code
49933
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katy Piton
Email
kapiton@chu-angers.fr
First Name & Middle Initial & Last Name & Degree
Sandrine Laboureau
Facility Name
CHU Hôpitaux de Rouen
City
Bois-Guillaume
ZIP/Postal Code
76230
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hind Berrahmoune
Email
hind.berrahmoune@chu-rouen.fr
First Name & Middle Initial & Last Name & Degree
Herve Lefebvre, MD
Facility Name
Hospices Civils of Lyon
City
Bron
ZIP/Postal Code
69677
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sihem Zaghdoud
Email
sihem.zaghdoud@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Hélène Lasolle, MD
Facility Name
Lille University Hospital
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Geraldine Lavergne
Email
geraldine.lavergne@chru-lille.fr
First Name & Middle Initial & Last Name & Degree
Marie-Christine Vantyghem
Facility Name
Hôpital de la Conception
City
Marseille
ZIP/Postal Code
13385
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mona Sahnoun
Email
Mouna.SAHNOUN@ap-hm.fr
First Name & Middle Initial & Last Name & Degree
Frederic Castinetti
Facility Name
CHU Bordeaux Hopital Haut
City
Pessac
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amandine Galioot
Email
amandine.galioot@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
Antoine Tabarin
Facility Name
C.M.D.T.A. Neomed
City
Braşov
ZIP/Postal Code
500283
Country
Romania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Purcaru
Email
office@neomed.org
First Name & Middle Initial & Last Name & Degree
Oana Capraru, MD
Facility Name
Institutul National de Endocrinologie
City
Bucharest
ZIP/Postal Code
11863
Country
Romania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monica Gheorghiu
Email
monicagheorghiu@yahoo.com
First Name & Middle Initial & Last Name & Degree
Corin Badiu, MD
Facility Name
Spitalul Clinic Judeţean de Urgenţe "Sf. Spiridon"
City
Iași
ZIP/Postal Code
700115
Country
Romania
Individual Site Status
Withdrawn
Facility Name
Universitatea de Medicina si Farmacie Targu Mures - Spitalul Clinic Judetean de Urgenta Targu Mures
City
Târgu-Mureş
ZIP/Postal Code
540136
Country
Romania
Individual Site Status
Withdrawn
Facility Name
University Hospital of Wales
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diego Esteban
Email
Diego.Esteban@wales.nhs.uk
First Name & Middle Initial & Last Name & Degree
Aled Rees, MD
Facility Name
Leeds Teaching Hospitals NHS Trust
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Bailey
Email
julie.bailey10@nhs.net
First Name & Middle Initial & Last Name & Degree
Afroze Abbas, MD
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SW9 8RR
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joyce Aseyemi
Email
joyce.adeyemi@nhs.net
First Name & Middle Initial & Last Name & Degree
Ling Ling Chuah
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Withdrawn
Facility Name
Manchester University NHS Foundation Trust - Wythenshawe Hospital
City
Manchester
ZIP/Postal Code
M23 9QZ
Country
United Kingdom
Individual Site Status
Withdrawn
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
ZIP/Postal Code
M5 5AP
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Summersgill
Email
Christina.Summersgill@nca.nhs.uk
First Name & Middle Initial & Last Name & Degree
Tara Kearney, MD
Facility Name
University Hospital Southampton NHS Foundation Trust - Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle Beveridge
Email
Michelle.Beveridge@uhs.nhs.uk
First Name & Middle Initial & Last Name & Degree
Jana Bujanova, MD

12. IPD Sharing Statement

Learn more about this trial

SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor

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