Polycystic Kidney Disease, Autosomal DominantPhase 1NCT04536688
A Study of RGLS4326 in Patients With Autosomal Dominant Polycystic Kidney Disease
A Phase 1 study testing RGLS4326 in people with Polycystic Kidney Disease, Autosomal Dominant, run by Regulus Therapeutics Inc. at 12 sites in United States.
Trial summary
Primary Objective To assess the dose response relationship between RGLS4326 and ADPKD biomarkers Secondary Objectives To characterize the pharmacokinetic (PK) properties of RGLS4326 in plasma and urine To assess the safety and tolerability of RGLS4326 Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Polycystic Kidney Disease, Autosomal Dominant
- What is being tested?
- RGLS4326
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 12 sitesUnited States
- Study dates
- 13 Oct 2020to 12 Nov 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ADPKD patients 18 to 70 years old
- Class 1C, 1D, or 1E Mayo Imaging Classification of ADPKD (based upon prior MRI or CT Scan or MRI obtained during screening)
- Estimated GFR at Screening between 30 to 90 mL/min/1.73 m^2 calculated by the investigator using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)
- Body mass index (BMI) between 18 and 35 kg/m^2
- If the patient has hypertension, the antihypertensive regimen must be stable for at least 28 days prior to randomization and the blood pressure adequately controlled prior to randomization
- Female patients of childbearing potential must not be lactating and must have no plans to become pregnant during the course of the study through 28 days after the last dose of study drug. Female patients of childbearing potential who are heterosexual must agree to use one of the following methods of contraception considered to be highly effective (i.e., results in <1% failure rate when used consistently and correctly) from screening through 28 days after the last dose of study drug:
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- Intrauterine device (IUD) or intrauterine system (IUS) in place for at least 3 months prior to first dose
- Partner has had a vasectomy. Vasectomy in the partner is only considered to be highly effective provided the partner is the sole sexual partner of the female patient of childbearing potential and the vasectomized partner has had a medical assessment of the surgical success.
- Stable hormonal contraception associated with inhibition of ovulation (with approved oral, transdermal, or depot regimen) for at least 3 months prior to first dose
- Bilateral tubal occlusion
- Female patient of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose of study drug:
- Hysterectomy
- Bilateral oophorectomy
- Bilateral tubal occlusion
- Bilateral salpingectomy or be postmenopausal with no periods for at least 1 year prior to the first dose of study drug.
- Male patients must agree to use a condom during heterosexual intercourse and to not have unprotected sexual intercourse with a female who is pregnant or breastfeeding from screening through 28 days after the last dose of study drug; and must agree to refrain from sperm donation for at least 90 days after the last dose of study drug
- Screening hematology and clinical chemistries must meet the following criteria:
- Platelets >150 x 10^9/L
- Total white blood cell (WBC) count >3.0 x 10^9/L and absolute neutrophil count >1.5 x 10^9/L
- Hemoglobin >12 g/dL for females and >13.5 g/dL for males
- Total and direct bilirubin <1.5x upper limit of normal (ULN), unless elevated bilirubin is associated with a known benign condition (e.g., Gilbert's syndrome)
- Alanine aminotransferase (ALT) <1.5x ULN
- Aspartate aminotransferase (AST) <1.5x ULN
- Alkaline phosphatase (ALP) <1.5x ULN
- Gamma-glutamyl transferase (GGT) <2x ULN Note: At the discretion of the Investigator, screening laboratory testing may be repeated once to confirm out of range (exclusionary) results.
- Able to understand all study procedures in the informed consent form (ICF) and willing to comply with all aspects of the protocol
Who cannot join
- Administration of tolvaptan in the 28 days before randomization
- Participation in another investigational interventional study within 28 days or 5 half-lives, whichever is longer, before randomization (e.g., bardoxolone, lixivaptan, tesevatinib, venglustat)
- A history of drug and/or alcohol abuse within the past year
- Active infection of the urinary tract (e.g., kidney, bladder, etc.)
- Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
- Only one kidney or kidney transplant recipient.
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- Patient has concurrent medical condition (e.g., significant infection, other kidney disease, neurologic condition such as seizures, etc.) or social situation that may either present a safety risk or noncompliance with the study procedures
- History of active malignancy within 5 years of randomization, except adequately treated basal cell or squamous cell carcinoma of the skin
- History of a clinically significant reaction to an oligonucleotide compound
- Significant blood loss or blood donation within the 28 days prior to randomization or plasma donation within 7 days prior to randomization
- A tattoo or scarring on the abdomen or any other condition large enough to interfere with the ability to assess injection site reactions
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Accel Research Sites- Mid-Florida Kidney and Hypertension Care
Altamonte Springs, Florida, 32701
Tufts Medical Center
Boston, Massachusetts, 02111
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
UT Southwestern Medical Center
Dallas, Texas, 75390
University of Kansas Medical Center
Kansas City, Kansas, 66160
Balboa Nephrology Medical Group
La Mesa, California, 91942
Academic Medical Research Institute
Los Angeles, California, 90022
Yale Nephrology Clinical Research
New Haven, Connecticut, 06510
Mayo Clinic
Rochester, Minnesota, 55904
St. Clair Nephrology Research
Roseville, Michigan, 48066
ICON Early Phase Services
San Antonio, Texas, 78209
Swedish Polycystic Kidney Disease Center
Seattle, Washington, 98104
About this study
Official title: A Phase 1b, Multicenter, Open-Label, Adaptive Design Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RGLS4326 Administered Via SC Injection to Patients With Autosomal Dominant Polycystic Kidney Disease
Primary Objective
- To assess the dose response relationship between RGLS4326 and ADPKD biomarkers
Secondary Objectives
- To characterize the pharmacokinetic (PK) properties of RGLS4326 in plasma and urine
- To assess the safety and tolerability of RGLS4326
Read the detailed description
This is a Phase 1b, open-label, adaptive design dose-ranging study to evaluate ADPKD biomarkers, PK, safety, tolerability, and pharmacodynamics (PD) of RGLS4326 administered via SC injection to patients with ADPKD. The goal is to assess the dose response relationship between RGLS4326 and ADPKD biomarkers. The study will consist of three sequential cohorts with approximately 18 to 27 subjects total.
- Being tested
- RGLS4326
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RGLS4326Drug
Solution for subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| RGLS4326 1 mg/kg Q2W | Experimental | Eligible participants will receive subcutaneous injection of 1 mg/kg of RGLS4326 every other week for 4 doses Receives: Drug: RGLS4326 |
| RGLS4326 0.3 mg/kg Q2W | Experimental | Eligible participants will receive subcutaneous injection of 0.3 mg/kg of RGLS4326 every other week for 4 doses Receives: Drug: RGLS4326 |
| RGLS4326 0.1 or 0.5 mg/kg Q2W | Experimental | Eligible participants will receive subcutaneous injection of 0.1 or 0.5 mg/kg of RGLS4326 every other week for 4 doses Receives: Drug: RGLS4326 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in primary biomarker levels from baseline
Changes in polycystin-1 (PC-1) and polycystin-2 (PC-2) protein levels in urinary exosomes from baseline to Day 44
Measured: Baseline to Day 44
Secondary outcomes (7)
Changes in secondary biomarker levels from baseline
Changes in neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in urine from baseline to Day 44
Measured: Baseline to Day 44
Pharmacokinetics (Cmax)
Maximum concentration (Cmax) of RGLS4326 in plasma following RGLS4326 treatment
Measured: Baseline to Day 44
Pharmacokinetics (Tmax)
Time to maximum concentration (Tmax) of RGLS4326 in plasma following RGLS4326 treatment
Measured: Baseline to Day 71
Pharmacokinetics (AUC)
Area under the curve (AUC) of RGLS4326 in plasma following RGLS4326 treatment
Measured: Baseline to Day 71
Number of participants with anti-drug antibodies (ADAs)
Incidence of ADAs following RGLS4326 treatment from baseline to Day 71
Measured: Baseline to Day 71
Titre of anti-drug antibodies (ADAs) in patients with ADAs
Titre of ADAs following RGLS4326 treatment from baseline to Day 71
Measured: Baseline to Day 71
Safety profile
Incidence of AEs, lab abnormalities, and ECG abnormalities following RGLS4326 treatment
Measured: Baseline to Day 71
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2020
- Study start13 Oct 2020
- Primary completion12 Nov 2021
- Study completion12 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Kidney Disease, Autosomal DominantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Cohorts will be enrolled and treated sequentially. Dosing decisions will be made based on prior cohort's safety and biomarker data. Six to 9 subjects will be enrolled in each cohort based on the magnitude and/or variability of the increase in PC1 and PC2 or to allow for replacement of subjects that do not complete the study. The highest dose (1 mg/kg) will be administered in cohort 1. If the Sponsor determines that the increase in PC1 and PC2 from baseline for cohort 1 is inadequate, the study may be stopped for futility. If the Sponsor determines that the increase from baseline for cohort 1 is adequate, then 0.3 mg/kg will be administered in cohort 2. Based on the increase of PC1 and PC2 from baseline in cohort 2, Sponsor may determine a higher dose needs to be evaluated, then 0.5 mg/kg will be administered in cohort 3. If the Sponsor determines that lower dose needs to be evaluated, then 0.1 mg/kg will be administered in cohort 3.
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regulus Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Karl Cremer, PharmD, Study director, Regulus Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04536688
- Sponsor's protocol ID
- RGLS4326-03
- Status last verified
- Dec 2021
- First submitted
- 24 Aug 2020
- Last updated
- 15 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Multicenter, Open-Label, Adaptive Design Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RGLS4326 Administered Via SC Injection to Patients With Autosomal Dominant Polycystic Kidney Disease
- ClinicalTrials.gov ID
- NCT04536688
- Acronym / sponsor ID
- RGLS4326-03
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Regulus Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Oct 2020 (actual)
- Primary completion
- 12 Nov 2021 (actual)
- Study completion
- 12 Nov 2021 (actual)
- First posted
- 3 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective
- To assess the dose response relationship between RGLS4326 and ADPKD biomarkers
Secondary Objectives
- To characterize the pharmacokinetic (PK) properties of RGLS4326 in plasma and urine
- To assess the safety and tolerability of RGLS4326
Detailed description
This is a Phase 1b, open-label, adaptive design dose-ranging study to evaluate ADPKD biomarkers, PK, safety, tolerability, and pharmacodynamics (PD) of RGLS4326 administered via SC injection to patients with ADPKD. The goal is to assess the dose response relationship between RGLS4326 and ADPKD biomarkers. The study will consist of three sequential cohorts with approximately 18 to 27 subjects total.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Cohorts will be enrolled and treated sequentially. Dosing decisions will be made based on prior cohort's safety and biomarker data. Six to 9 subjects will be enrolled in each cohort based on the magnitude and/or variability of the increase in PC1 and PC2 or to allow for replacement of subjects that do not complete the study. The highest dose (1 mg/kg) will be administered in cohort 1. If the Sponsor determines that the increase in PC1 and PC2 from baseline for cohort 1 is inadequate, the study may be stopped for futility. If the Sponsor determines that the increase from baseline for cohort 1 is adequate, then 0.3 mg/kg will be administered in cohort 2. Based on the increase of PC1 and PC2 from baseline in cohort 2, Sponsor may determine a higher dose needs to be evaluated, then 0.5 mg/kg will be administered in cohort 3. If the Sponsor determines that lower dose needs to be evaluated, then 0.1 mg/kg will be administered in cohort 3.
| Arm | Type | Receives |
|---|---|---|
| RGLS4326 1 mg/kg Q2W | Experimental | Drug: RGLS4326Eligible participants will receive subcutaneous injection of 1 mg/kg of RGLS4326 every other week for 4 doses |
| RGLS4326 0.3 mg/kg Q2W | Experimental | Drug: RGLS4326Eligible participants will receive subcutaneous injection of 0.3 mg/kg of RGLS4326 every other week for 4 doses |
| RGLS4326 0.1 or 0.5 mg/kg Q2W | Experimental | Drug: RGLS4326Eligible participants will receive subcutaneous injection of 0.1 or 0.5 mg/kg of RGLS4326 every other week for 4 doses |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Male or female ADPKD patients 18 to 70 years old
- Class 1C, 1D, or 1E Mayo Imaging Classification of ADPKD (based upon prior MRI or CT Scan or MRI obtained during screening)
- Estimated GFR at Screening between 30 to 90 mL/min/1.73 m^2 calculated by the investigator using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)
- Body mass index (BMI) between 18 and 35 kg/m^2
- If the patient has hypertension, the antihypertensive regimen must be stable for at least 28 days prior to randomization and the blood pressure adequately controlled prior to randomization
Key exclusion criteria (11 listed)
- Administration of tolvaptan in the 28 days before randomization
- Participation in another investigational interventional study within 28 days or 5 half-lives, whichever is longer, before randomization (e.g., bardoxolone, lixivaptan, tesevatinib, venglustat)
- A history of drug and/or alcohol abuse within the past year
- Active infection of the urinary tract (e.g., kidney, bladder, etc.)
- Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RGLS4326Solution for subcutaneous injection | Drug | RGLS4326 0.1 or 0.5 mg/kg Q2W, RGLS4326 0.3 mg/kg Q2W, RGLS4326 1 mg/kg Q2W |
Primary outcome
Changes in primary biomarker levels from baseline
Time frame: Baseline to Day 44
Changes in polycystin-1 (PC-1) and polycystin-2 (PC-2) protein levels in urinary exosomes from baseline to Day 44
7 secondary outcomes
Changes in secondary biomarker levels from baseline
Time frame: Baseline to Day 44
Pharmacokinetics (Cmax)
Time frame: Baseline to Day 44
Pharmacokinetics (Tmax)
Time frame: Baseline to Day 71
Pharmacokinetics (AUC)
Time frame: Baseline to Day 71
Number of participants with anti-drug antibodies (ADAs)
Time frame: Baseline to Day 71
Titre of anti-drug antibodies (ADAs) in patients with ADAs
Time frame: Baseline to Day 71
Safety profile
Time frame: Baseline to Day 71
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karl Cremer, PharmD study director
Regulus Therapeutics
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RGLS4326 in people with Polycystic Kidney Disease, Autosomal Dominant, run by Regulus Therapeutics Inc. at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in primary biomarker levels from baseline (time frame: Baseline to Day 44). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2021.