Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Tolerability, and Efficacy of CLTX-305 in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04581629
Recruitment Status : Recruiting
First Posted : October 9, 2020
Last Update Posted : October 27, 2020
Sponsor:
Information provided by (Responsible Party):
Calcilytix Therapeutics, Inc.

Brief Summary:
A Phase IIb open label, dose finding study to evaluate the Safety, Tolerability and Efficacy of CLTX-305 in Autosomal Dominant Hypocalcemia (ADH) Type 1

Condition or disease Intervention/treatment Phase
Autosomal Dominant Hypocalcemia (ADH) Drug: CLTX-305 Phase 2

Detailed Description:

Autosomal dominant hypocalcemia Type 1 is a rare familial genetic form of hypoparathyroidism. Autosomal Dominant Hypocalcemia (ADH) Type 1 is passed down from affected mothers or fathers to their children.

This is a Phase llb open label, dose finding study to evaluate the safety and tolerability of CLTX-305 (encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1 as well as the effects of CLTX-305 (encaleret) on blood calcium concentration.

The estimated duration of this study is 12 months. This study plans to evaluate multiple doses of the investigational drug CLTX-305 (encaleret), in addition to safety and efficacy. CLTX-305 is administered orally.

The study is divided into 3 Periods:

Periods 1 and 2: Up to 8 study participants will be admitted to the NIH Clinical Center for 7 days, where they will be administered different doses of CLTX-305 (encaleret) for up to 5 days.

Period 3: 24 weeks during which eligible study participants who completed Period 2 will take CLTX-305 (encaleret) at home

Study participants may:

  • Participate in Period 1
  • Participate in Period 2
  • Participate in both Period 1 and Period 2
  • Participate in Period 3 after completing Period 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIb, Open-label Dose-ranging Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics, and Efficacy of CLTX-305 in Autosomal Dominant Hypocalcemia (ADH) Type 1
Actual Study Start Date : September 15, 2020
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Experimental: CLTX-305
CLTX-305 (encaleret) dose finding study to determine safety, tolerability and dose response during three (3) periods of this study with dose levels at QD and BID; up to 26 weeks of active treatment per participant
Drug: CLTX-305
  • Period 1: Once or twice daily of CLTX-305 for 5 days
  • Period 2: Twice daily doses of CLTX-305 for 5 days
  • Period 3: Individualized dose titration of CLTX-305 for up to 24 weeks
Other Name: Encaleret




Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 1 year ]
    An Adverse Event (AE) is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study are reported as adverse events.

  2. Change From baseline in albumin-corrected blood calcium concentrations (cCa) after treatment with CLTX-305 [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]

Secondary Outcome Measures :
  1. Change from baseline in intact PTH blood concentration profile after treatment with CLTX-305 [ Time Frame: Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each ]
  2. Change from baseline in urinary calcium clearance fractional excretion [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  3. Change from baseline in urinary clearance (24-hour total excretion) [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  4. Change from baseline in Serum levels of 1,25-(OH)2 Vitamin D [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  5. Change from baseline in blood magnesium levels [ Time Frame: Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each ]
  6. Change from baseline in blood phosphate levels [ Time Frame: Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each ]
  7. Change from baseline in blood creatinine levels [ Time Frame: Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each ]
  8. Change from baseline in blood magnesium levels [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  9. Change from baseline in blood phosphate levels [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  10. Change from baseline in blood creatinine levels [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  11. Change from baseline in urinary content of magnesium [ Time Frame: Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each ]
  12. Change from baseline in urinary content of phosphate [ Time Frame: Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each ]
  13. Change from baseline in urinary content of creatinine [ Time Frame: Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each ]
  14. Change from baseline in urinary content of magnesium [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  15. Change from baseline in urinary content of phosphate [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  16. Change from baseline in urinary content of creatinine [ Time Frame: Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  17. Change from baseline in bone marker - blood collagen cross-linked C-telopeptide (CTx) [ Time Frame: Periods 1, 2 and 3; 46 weeks - Periods 1 and 2 lengths are 7 days each, Period 3 length is 24 weeks ]
  18. Change from baseline in bone marker - blood procollagen type 1 N-propeptide (P1NP) [ Time Frame: Periods 1, 2 and 3; 46 weeks - Periods 1 and 2 lengths are 7 days each, Period 3 length is 24 weeks ]
  19. Maximum Observed Plasma Concentration (Cmax) of CLTX-305 [ Time Frame: Period 1; Day 1, 2, 4, and 5 (pre-dose and out to 13 hours post dose) - Period 1 length is 7 days ]
  20. Maximum Observed Plasma Concentration (Cmax) of CLTX-305 [ Time Frame: Period 2; Day 1, 2, 4, and 5 (pre-dose and out to 13 hours post dose) - Period 2 length is 7 days ]
  21. Maximum Observed Plasma Concentration (Cmax) of CLTX-305 [ Time Frame: Period 3; week 24 (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  22. Area Under the Plasma Concentration Versus Time Curve (AUC) of CLTX-305 [ Time Frame: Period 1; Day 1, 2, 4, and 5 (pre-dose and out to 13 hours post dose) - Period 1 length is 7 days ]
  23. Area Under the Plasma Concentration Versus Time Curve (AUC) of CLTX-305 [ Time Frame: Period 2; Day 1, 2, 4, and 5 (pre-dose and out to 13 hours post dose) - Period 2 length is 7 days ]
  24. Area Under the Plasma Concentration Versus Time Curve (AUC) of CLTX-305 [ Time Frame: Period 3; week 24 (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]
  25. Apparent Terminal Plasma Half-Life (t1/2) of CLTX-305 [ Time Frame: Period 3; week 24 (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be able to understand and sign a written informed consent or assent form, which must be obtained prior to initiation of study procedures.
  • Age ≥ 16 years
  • Postmenopausal women are allowed to participate in this study
  • Body mass index (BMI) ≥ 18.5 to < 39 kg/m2
  • Have an activating mutation of the CASR gene

Exclusion Criteria:

  • History of treatment with PTH 1-84 or 1-34 within the previous 3 months
  • History of hypocalcemic seizure within the past 3 months
  • Blood 25-OH Vitamin D level < 25 ng/mL
  • Pregnant or nursing (lactating) women
  • History of drug or alcohol dependency within 12 months preceding the Screening Visit
  • History of thyroid or parathyroid surgery
  • Current participation in other investigational drug studies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04581629


Contacts
Layout table for location contacts
Contact: Medical Information MedInfo@calcilytix.com MedInfo@calcilytix.com

Locations
Layout table for location information
United States, Maryland
National Institute of Health Recruiting
Bethesda, Maryland, United States, 20892
Contact: Karen A Pozo, R.N.    301-827-1138    karen.pozo@nih.gov   
Contact: NIH Clinical Center Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Principal Investigator: Rachel I. Gafni, MD         
Sponsors and Collaborators
Calcilytix Therapeutics, Inc.
Layout table for additonal information
Responsible Party: Calcilytix Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04581629    
Other Study ID Numbers: CLTX-305-201
First Posted: October 9, 2020    Key Record Dates
Last Update Posted: October 27, 2020
Last Verified: October 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthrogryposis
Hypocalcemia
Joint Diseases
Musculoskeletal Diseases
Muscular Diseases
Musculoskeletal Abnormalities
Congenital Abnormalities
Calcium Metabolism Disorders
Metabolic Diseases
Water-Electrolyte Imbalance